No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
NeuroAid (MLC601) versus piracetam in the recovery of post-infarct homonymous hemianopsia
Abstract
In the clinic, the natural recovery rate of homonymous hemianopsia caused by occipital lobe infarction is low. At present, ideal therapeutic effects of piracetam for improving visual field defects following homonymous hemianopsia do not exist. The present randomized, controlled study compared the effects of NeuroAid (MLC601) versus piracetam for improving visual field defects in post-infarct homonymous hemianopsia patients matched for age and sex. After 3 months of treatment with NeuroAid (MLC601) or piracetam, visual field defects were significantly improved, compared with prior to treatment (P < 0.001). After treatment with MLC601, relative reduction of right and left visual field defects was 45% and 45.7%, respectively, while relative reduction after treatment with piracetam was 32.7% and 30.3%, respectively. These findings suggested that MLC601 was superior to piracetam for reducing visual field defects in homonymous hemianopsia patients.
... [1][2][3][4][5][6][7] Clinical trials of MLC601/MLC901 and systematic reviews of those trials showed benefit in improving functional and neurological recovery in patients with ischaemic stroke. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] As part of further drug development, a simplified formulation (MLC1501) would have the advantages of reduced variability, reduced risk of contamination, avoidance of unnecessary animal slaughter, reduced daily number of capsules to improve compliance and lower cost. Literature reviews and a series of in vitro and in vivo experiments were performed to assess the effects of the different herbs in the parent formulation against neuronal degeneration and cerebral ischaemia. ...
... Furthermore, with only four ingredients, MLC1501 is expected to have a comparable or even better efficacy-tosafety profile than MLC601 and MLC901. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The safety of MLC1501 was demonstrated in two phase I studies on healthy subjects in an investigational new drug application under the botanical drug framework of the US Food and Drug Administration. 27 In the dose-escalation study, MLC1501 was shown to be safe and well tolerated. ...
... The MLC1501 study Assessing Efficacy in post-STrOke Subjects with mOtor deficits (MAESTOSO) study of MLC1501 was designed based on recent insights on stroke recovery trials as well as the extensive knowledge gained from earlier studies on MLC601 and MLC901 on the role of baseline stroke severity and treatment window. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] The target study population in MAESTOSO are patients with ischaemic stroke who still have clinically important deficits in the postacute period. ...
Background
MLC1501, consisting of four herbs, that is, Radix Astragali , Radix Angelicae sinensis , Rhizoma Chuanxiong , Radix Polygalae , has the same pharmacological properties as its precursors MLC601 and MLC901 which contain extracts of nine herbs and showed neuroprotective, anti-inflammatory and neurorestorative properties in non-clinical models, as well as clinical benefits in improving functional and neurological recovery after brain injuries.
Aims
To determine the efficacy of MLC1501 on motor recovery as measured by Fugl-Meyer motor Assessment (FMA) total score at 24 weeks in patients with ischaemic stroke (IS).
Design
A total of 300 patients aged >18 years, diagnosed with IS in the prior 2–10 days, with National Institute of Health Stroke Scale (NIHSS) total score of 8–18 and a combined score of ≥3 on NIHSS motor items 5A, 5B, 6A and/or 6B, will be randomised in a 1:1:1 ratio to receive oral placebo, MLC1501 low dose or MLC1501 high dose for 6 months. The study is governed by a Steering Committee. An independent Data Monitoring Committee oversees patient safety.
Outcomes
The primary outcome is mean change from baseline in FMA total score at 24 weeks. Efficacy outcomes evaluated in person at baseline, 12 weeks and 24 weeks include the FMA (total, upper extremity and lower extremity motor scores), modified Rankin Scale (mRS), Patient-Reported Outcomes Measurement Information System–Global Health (PROMIS-10) and NIHSS. Additionally, telephone assessment at week 4 includes the simplified mRS and PROMIS-10.
Safety will be evaluated by standard assessments and occurrence of adverse events over the duration of the study.
Discussion
Interventions that enhance recovery beyond the acute period of stroke are needed. MLC1501 has a good safety profile as well as potential to be a treatment for recovery after brain injury. The results of this study will provide objective level B evidence on the efficacy of MLC1501 on long-term recovery and safety of 24 weeks of treatment among patients with IS.
Trial registration number
NCT05289947 .
... 8 One trial compared DPC with Troxerutin. 10 One trial compared MLC601 with piracetam. 17 Two articles compared DPC with Buchangnaoxintong. 11,14 One of these articles reported results of two RCTs. ...
... Four trials reported the effective rate, [8][9][10][11] two trials reported FMA, 3,15 five articles reported degree of neural functional recovery, 8,9,14,15,18 two trials reported NIHSS, 15,18 two trials reported BI and reported mRS, 16,18 and five articles reported safety observations. [11][12][13][14]18 One article reported FIM, 15 one provided data on visual field defects recovery, 17 one reported mini-mental state examination (MMSE) results, 18 one reported information on intracranial hematoma reabsorption, 8 one reported MFV, 16 and eight articles reported adverse events 3,11-17 ( Table 1). ...
... Eleven of the included articles described random sequence generation methods. 3,8,[10][11][12][13][14][15][16][17][18] Two articles reported the methods of allocation concealment. 14,18 Five articles were participants and personnel blinding, 3,[14][15][16]18 and five articles were outcome assessment. ...
To evaluate the efficacy and safety of Danqipiantan capsule (DPC) for the treatment of stroke.
PubMed, China Science And Technology Journal Database, Wanfang Database, Chinese periodicals in the China National Knowledge Infrastructure, and the General Hospital of Tianjin Medical University's Library were searched until July 2012. Randomized controlled trials (RCTs) and observational studies that reported the use of DPC for treatment of stroke were selected.
Eleven articles that included 12 RCTs, and 2 articles that included 3 observational studies were identified. A total of 2590 patients participated inthe studies. We found that there was a signficant statistical difference between DPC treatment groups and the control groups in terms of the effective rate [risk ratio (RR), 1.14; 95% confidence intervals (CI), 1.04, 1.25; P = 0.01], Fugl-Meyer Assessment Scale [weighted mean difference (WMD), 9.77; 95% C (4.84, 14.70); P = 0.00], Barthel Index [WMD = 6.40; 95% Cl (3.15, 9.65)], and mean flow velocity [WMD = 5,79; 95% CI (1.64, 9.94)]. There were no significant differences for The National Institutes of Health Stroke Scale [WMD = 0.60; 95% CI (-1.09, 2.29)], visual field defects [left visual field: WMD = -203.10; 95% CI (-424.41, 18.21); right visual field: WMD = -172.60; 95% CI (-409.29, 64.09)] or the functional independence measure [WMD = -7.90; 95% Cl (-16.64, 0.84)]. Seven articles that included eight RCTs reported the safety of DPC treatment. Two articles that included three observational studies also reported beneficial effects for DPC. Because the Chinese studies were of poor methodological quality, and most of the sample sizes were small, our analysis was likely affected by bias.
DPC has a beneficial effect and is relatively safe when used for the treatment of stroke.
... The clinical data on NeuroAiD, however, are most well-reported in stroke. A systematic review of randomized clinical trials on NeuroAiD showed its benefits in improving functional outcomes and neurological deficits with 3 months treatment among patients with ischemic stroke in the preceding 1 week to 6 months [20][21][22][23][24][25]. Subsequently, NeuroAiD was investigated in acute ischemic stroke within 72 hours of onset which demonstrated the treatment effect to be larger in postacute and relatively more severe stroke at 3 months [26][27][28][29]. ...
... The common side effects reported from NeuroAiD were mostly mild and transient. Excellent clinical safety has been demonstrated in published clinical trials which reported the more common adverse events being gastrointestinal (nausea, vomiting, discomfort, diarrhea, dry mouth) and headache [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Safety studies in humans have shown that NeuroAiD, given alone or combined with aspirin, had no effect on clotting and coagulation [35]. ...
Background
Spinal cord injury (SCI) is a devastating condition with limited therapeutic options despite decades of research. Current treatment options include use of steroids, surgery, and rehabilitation. Nevertheless, many patients with SCI remain disabled. MLC601 (NeuroAiD), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries and may have a potential role in improving recovery after SCI.
Objective
The aim of this study is to evaluate the safety and efficacy of NeuroAiD amongst people who sustain SCI in the study setting.
Methods
Spinal Cord Injury—Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN) is a prospective cohort study of patients with moderately severe to severe SCI, defined as American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B. These patients will be treated with open-label NeuroAiD for 6 months in addition to standard care and followed for 24 months. Anonymized data will be prospectively collected at baseline and months 1, 3, 6, 12, 18, and 24 and will include information on demographics; main diagnostics; and neurological and functional state assessed by the Spinal Cord Independence Measure, ASIA—International Standard for Neurological Classification Spinal Cord Injury, and Short Form (SF-8) Health Survey. In addition, NeuroAiD treatment, compliance, concomitant therapies, and side effects, if any, will be collected. Investigators will use a secured online system for data entry. The study is approved by the ethics committee of Hospital University Kebangsaan Malaysia.
Results
The coprimary endpoints are safety, AIS grade, and improvement in ASIA motor score at 6 months. Secondary endpoints are AIS grade, ASIA motor scores and sensory scores, Spinal Cord Independence Measure (SCIM), SF-8 Health Survey, and compliance at other time points.
Conclusions
SATURN investigates the promising role of NeuroAiD in SCI especially given its excellent safety profile. We described here the protocol and online data collection tool we will use for this prospective cohort study. The selection of moderately severe to severe SCI provides an opportunity to investigate the role of NeuroAiD in addition to standard rehabilitation in patients with poor prognosis. The results will provide important information on the feasibility of conducting larger controlled trials to improve long-term outcome of patients with SCI.
Trial Registration
Clinicaltrials.gov NCT02537899; https://clinicaltrials.gov/ct2/show/NCT02537899 (Archived by WebCite at http://www.webcitation.org/6m2pncVTG)
... A systematic review of randomised clinical trials on NeuroAiD showed its benefits in improving functional outcomes and neurological deficits with 3 months treatment among patients with ischaemic stroke in the preceding 1 week to 6 months. [8][9][10][11][12][13] Subsequently, NeuroAiD was Strengths and limitations of this study ▪ Proactive collection of safety data in the realworld setting. ▪ Does not interfere with clinical decision-making of physicians and patients. ...
... Excellent clinical safety has been demonstrated in published clinical trials which reported the more common adverse events (AEs) being gastrointestinal symptoms (nausea, vomiting, discomfort, diarrhoea, dry mouth), and headache. [8][9][10][11][12][13] Safety studies in humans have shown that NeuroAiD, given alone or combined with aspirin, had no effect on clotting and coagulation. 28 Furthermore, there was no effect on haematological, haemostatic and biochemical parameters, and/or ECG in normal patients and patients with stroke, even when started within 48 h of stroke onset. ...
Introduction:
NeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting.
Methods and analysis:
The NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information.
Ethics and dissemination:
Doctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements.
Trial registration number:
NCT02536079.
... 11 More studies have since been published assessing the benefit and safety of MLC601 in nonacute stroke patients using different clinical outcomes. [12][13][14][15][16][17][18][19] Although most patients experience some spontaneous recovery in the months after a stroke, the degree and timing of recovery are variable. Improving functional outcomes through specific interventions is a relatively unexplored area of great public health potential. ...
... MLC601 or matching placebo was given at a dose of 4 capsules 3 times daily for 3 months, as in previous clinical trials. [11][12][13][14][15][16][17][18] MLC601 and matching placebo were provided by Moleac (Singapore). Each 400 mg MLC601 capsule contains 9 herbal components (extracts derived from raw herbs consisting of Radix astragali, Radix salviae miltorrhizae, Radix paeoniae rubra, Rhizoma chuanxiong, Radix angelicae sinensis, Carthamus tinctorius, Prunus persica, Radix polygalae, and Rhizoma acori tatarinowii) and 5 animal components (Hirudo, Eupolyphaga seu steleophaga, Calculus bovis artifactus, Buthus martensii, and Cornu saigae tataricae). ...
Background and purpose:
Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window.
Methods:
This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use.
Results:
The modified Rankin Scale shift analysis-adjusted odds ratio was 1.09 (95% confidence interval, 0.86-1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups.
Conclusions:
MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies.
Clinical trial registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00554723.
... Recently, many studies have been published on the efficacy and safety of MLC601 (NeuroAiD) in improving functional and neurological outcomes among nonacute poststroke patients [8][9][10][11][12][13][14][15]. MLC601 has been registered in the Philippines since 2006. ...
... Recent publications have shown benefit in the use of MLC601 in postischemic stroke patients. Many patients in these studies were nonacute and were included from within 1 week to up to 6 months since their stroke onset [8][9][10][11][12][13][14][15]. These studies offer an opportunity to intervene and improve functional and neurological outcomes further even if started in the recovery phase. ...
Aim. We aimed to assess the efficacy of MLC601 on functional recovery in patients given MLC601 after an ischemic stroke. Methods. This is a retrospective cohort study comparing poststroke patients given open-label MLC601 (n = 30; 9 female) for three months and matching patients who did not receive MLC601 from our Stroke Data Bank. Outcome assessed was modified Rankin Scale (mRS) at three months and analyzed according to: (1) achieving a score of 0-2, (2) achieving a score of 0-1, and (3) mean change in scores from baseline. Results. At three months, 21 patients on MLC601 became independent as compared to 17 patients not on MLC601 (OR 1.79; 95% CI 0.62-5.2; P = 0.29). There were twice as many patients (n = 16) on MLC601 who attained mRS scores similar to their prestroke state than in the non-MLC601 group (n = 8) (OR 3.14; 95% CI 1.1-9.27; P = 0.038). Mean improvement in mRS from baseline was better in the MLC601 group than in the non-MLC601 group (-1.7 versus -0.9; mean difference -0.73; 95% CI -1.09 to -0.38; P < 0.001). Conclusion. MLC601 improves functional recovery at 3 months postischemic stroke. An ongoing large randomized control trial of MLC601 will help validate these results.
... A randomized, open-label, controlled trial compared the effects of a 3-month course of MLC601 and piracetam in improving post-stroke homonymous hemianopsia (HH) in 40 patients [100]. At 3 months, visual field defects showed significant improvement compared to baseline (p < 0.001), with the relative improvement of right and left visual field defects being 45.7% in the MLC601 group and 30.3% and 32.7% in the piracetam group for the right and left visual fields, respectively. ...
Acute ischemic stroke (AIS) and traumatic brain injury (TBI) are two severe neurological events, both being major causes of death and prolonged impairment. Their incidence continues to rise due to the global increase in the number of people at risk, representing a significant burden on those remaining impaired, their families, and society. These molecular and cellular mechanisms of both stroke and TBI present similarities that can be targeted by treatments with a multimodal mode of action, such as traditional Chinese medicine. Therefore, we performed a detailed review of the preclinical and clinical development of MLC901 (NeuroAiDTMII), a natural multi-herbal formulation targeting several biological pathways at the origin of the clinical deficits. The endogenous neurobiological processes of self-repair initiated by the brain in response to the onset of brain injury are often insufficient to achieve complete recovery of impaired functions. This review of MLC901 and its parent formulation MLC601 confirms that it amplifies the natural self-repair process of brain tissue after AIS or TBI. Following AIS and TBI where "time is brain", many patients enter the post-acute phase with their functions still impaired, a period when "the brain needs time to repair itself". The treatment goal must be to accelerate recovery as much as possible. MLC901/601 demonstrated a significant reduction by 18 months of recovery time compared to a placebo, indicating strong potential for facilitating the improvement of health outcomes and the more efficient use of healthcare resources.
... Despite that, Kong and colleagues showed an alarming trend of hepatotoxicity and jaundice in patients taking NeuroAid II, causing them to withdraw from the study [20]. Other studies demonstrate milder side effects, especially nausea and vomiting [24,25]. This effect is greatly magnified by several risk factors, such as elderly age group and a more severe stroke [26]. ...
Background
NeuroAid II (MLC901) is a promising therapy for stroke patients who present outside of therapeutic window for reperfusion therapy. Studies have proven its efficacy in ischemic stroke; however, data of drug safety and combination with other medications especially anticoagulants are heterogenous. We report a possible case of hepatotoxicity induced by NeuroAid II in combination with anticoagulants.
Case presentation
We report an elderly patient who developed symptoms of cardioembolic stroke presented outside of time window for reperfusion therapy. He was started on a regiment of statins, anticoagulation, beta blockers and NeuroAid II. One month later he presented with deranged liver enzymes. Cessation of NeuroAid II resulted in rapid improvement of transaminitis within days.
Conclusions
We wish to highlight the potential harmful effect of administering NeuroAid II with an anticoagulant and the importance of routine follow-up and blood monitoring in the elderly patients with stroke.
... Animal and cell studies have shown that MLC901 stimulated natural processes of neural repair and neuroplasticity [29,30]. Clinical studies showed that its precursor, MLC601, improved motor, visual, and functional outcomes in patients with stroke at 3 months and up to 2 years [31][32][33]. Subanalyses of the large clinical trial showed larger treatment effects among patients with predictors of poor outcome, including worse baseline NIHSS, likely because they had more potential to benefit from treatment [26,34,35]. ...
Background. Improving our knowledge about the impact of restorative therapies employed in the rehabilitation of a stroke patient may help guide practitioners in prescribing treatment regimen that may lead to better post-stroke recovery and quality of life. Aims. To evaluate the neurological and functional recovery for 3 months after an acute ischemic stroke occurred within previous 3 months. To determine predictors of recovery. Design. Prospective observational registry. Population. Patients having suffered acute moderate to severe ischemic stroke of moderate to severe intensity within the previous 3 months with National Institutes of Health Stroke Scale (NIHSS) score from 10 to 20, 24 hours after arrival at emergency room (ER). Methods. All prespecified variables (sociodemographic and clinical data, lifestyle recommendations, rehabilitation prescription, and neurological assessments) were assessed at three visits, i.e., baseline (D0), one month (M1), and three months (M3). Results. Out of 143 recruited patients, 131 could be analysed at study entry within 3 months after stroke onset with a mean acute NIHSS score of 14.05, decreased to 10.8 at study baseline. Study sample was aged , with 49.2% of women. Neurorehabilitation treatment was applied to 9 of 10 patients from the acute phase and for three months with different intensities depending on the centre. A large proportion of patients recovered from severe dependency on activities of daily living (ADL) at D0 to a mild or moderate disability requiring some help at M3: mean ; ; ; all . Multivariate analyses integrating other regression variables showed a trend in favour of rehabilitation and revascularization therapies on recovery although did not reach statistical significance and that the positive predictors of recovery improvement were baseline BI score, time to treatment, and dietary supplement MLC901 (NurAiD™II). A larger percentage of patients with more severe stroke () who received MLC901 showed above median improvements on mRS compared to control group at M1 (71.4% vs. 29.4%; ) and M3 (85.7% vs. 50%; ). Older subjects and women tend to have less improvement by M3. Conclusions. Our study in patients with moderate to severe stroke shows overall recovery on neurological and functional assessments during the 3 months of study observation. Apart from demonstrating traditional “non-modifiable” predictors of outcome after stroke, like age, sex, and stroke severity, we also detected association between the use of dietary supplement MLC901 and recovery.
1. Introduction
Every year, nearly 120,000 people suffer from stroke in Spain, half of whom are disabled or suffer life-threatening sequelae. Although mortality and disability have declined in the last 20 years in all age groups and in both sexes in Spain, their incidence is expected to increase by 27%, according to data from the Spanish Society of Neurology [1]. The data further highlight stroke as the second leading cause of death overall in Spain, the leading cause of death among women, and the leading cause of disability in adults. The estimated incidence rate of stroke is 141 (95% confidence interval (CI) 125 to 158) per 100,000 inhabitants [2, 3]. Incidence rate clearly increases with age, with a peak at or above 85 years of age, and in-hospital mortality is 14%. Currently, more than 330,000 Spanish people have limited functional capacity due to stroke. Stroke survivors are at high risk for recurrent stroke and cardiovascular disease due to the pronounced aging of the population and the increased prevalence of risk factors in an increasingly elderly population [4]. In an epidemiological study of 321 patients diagnosed with stroke admitted to the stroke unit of 16 hospitals throughout Spain and followed up for 1 year, the total average cost per year was estimated at €27,711 per patient. Direct healthcare costs amounted to an average of €8491 (of which 68.8% was due to inpatient costs) and nonhealthcare costs to €18,643 per patient per year (of which 89.5% was due to informal care) [5].
Apart from the establishment of prevention programs and hospital stroke units, treatment of stroke is still limited in many settings. Even when patients receive acute stroke therapies, they may not derive benefit from such therapies, and as a result, a significant proportion of patients suffer from chronic sequelae and persistent deficits that significantly impact their ability to carry out their daily activities and quality of life [6].
Restorative therapies that improve neural repair and recovery in the postacute phase of stroke may reduce the overall long-term burden of stroke [7]. Thus, during the post-stroke rehabilitation process, different interventions may be prescribed as part of the holistic approach to help patients recover, combining different types of cognitive and motor therapies, as well as changes in lifestyle and use of supplements and herbal medicines [8, 9]. Improving our knowledge about the impact of these therapies employed in the rehabilitation of a stroke patient may help guide practitioners in prescribing treatment regimen that may lead to better post-stroke recovery and quality of life.
This observational study aimed to assess the rates of neurological and functional recovery over a 3-month follow-up period in a cohort of patients who have experienced a moderate to severe first-ever acute ischemic stroke and to determine predictors of greater recovery among this population.
2. Material and Methods
2.1. Study Design and Population
The EPICA study was a multicentre, prospective, observational study of patients who have suffered a moderate to severe acute ischemic stroke. The study was approved by the local ethics committee or institutional review board of each participating centre. Inclusion criteria are ≥18 years of age, first-ever ischemic stroke within three months prior to inclusion in the study, neurologically stable at the time of inclusion, pre-stroke modified Rankin Scale (mRS) ≤1, National Institute of Health Stroke Scale (NIHSS) score between 10 and 20 at 24 hours after arrival in the ER, and diagnosis confirmed by either computerized tomography (CT) or magnetic resonance imaging (MRI). Exclusion criteria are presence of intracranial haemorrhage, other intracranial pathologies, severe systemic diseases, or cognitive deficits that may potentially interfere with the requirements of the study.
Patients were included in the study as they come for consultation or admitted to the hospital if they meet the eligibility criteria. Written informed consent was obtained from all patients included in the study. Predefined data were ascertained from patients during the course of their participation in the study at inclusion (baseline, D0), one month (M1), and three months (M3). Throughout the study period, patients received standard treatments and interventions according to the medical judgment and prescription of their respective treating physicians, including cognitive and motor rehabilitation, lifestyle recommendations, such as diet and physical activity, and use of dietary supplements.
2.2. Study Variables
Data were collected using a case report form, either electronically or on paper. At baseline (D0), sociodemographic and clinical history including cardiovascular risk factors were collected. Details of the index stroke gathered at the time of hospital admission were ascertained at time of inclusion, including NIHSS within 24 hours of arrival in the ER, Glasgow Coma Scale (GCS), and pre-stroke mRS. The concurrent clinical status of the patient at study inclusion was assessed and recorded, using the same assessment scales with addition of Barthel index (BI) and Mini-Examen Cognoscitivo (MEC) of Lobo [10] (a Spanish adaptation of the Mini-Mental State Examination). Results of diagnostic imaging (CT or MRI) were recorded, as well as all medications or treatment regimen (e.g., thrombolysis and drug name) received by the patient.
The following assessments were performed at M1 and M3: NIHSS, GCS, mRS, MEC, and BI. At each visit, patients were asked about their rehabilitation program frequency, lifestyle (e.g., family situation, sleeping time, and physical activity), and dietary/feeding habits including the use of dietary supplements.
2.3. Statistical Analysis
Sample size was calculated using tests of comparison of means between independent groups to observe significant differences of greater than 0.5 in the M3 neurological recovery between the two extreme quartiles of the sample (P25 vs. P75). Based on an alpha of 0.05 and a power of 90%, a size of 70 patients per quartile or a total sample of 280 patients was planned.
The main assessments in the study were (i) mean grade of neurological and functional recovery by comparing scores between D0, M1, and M3 overall and by subgroups according to severity based on NIHSS (i.e., , ), and (ii) factors associated with higher probability of post-stroke recovery at M3.
Statistical analysis was performed using SPSS 22.0 statistical software for Windows. Baseline variables were presented using descriptive statistics. Continuous variables were described using central estimators (mean or median) and dispersion (standard deviation, SD, or interquartile range, IQR), while categorical variables were described as frequencies and percentages.
Since the planned sample size of 280 was not reached, the first to fourth quartile comparisons were substituted by median comparisons. Comparisons were made between groups using one-way analysis of variance (ANOVA) for continuous dependent variables and Pearson or Fisher’s exact test for categorical dependent variables. Student -test was used for variables with a normal distribution; otherwise, Wilcoxon test was used. Friedman test was used to determine the significance of evolution between visits as a whole. Results are given with values and 95% confidence interval (CI).
Multivariate analyses were performed for regression analysis and ANOVA for a dependent variable by one or more variables. Factor variables divide the population in groups. The general linear model (GLM) tests the null hypotheses on the effects of other variables on the means of several groups of a single dependent variable. For regression analysis, independent variables (predictors) are specified as covariates. The procedure to generate the multivariate models was based on univariate analyses of the main variables described in the previous section to determine which variables are to be included in the multivariable analyses. Binary logistic regression models were performed for dichotomous dependent variables. Continuous and ordinal variables were transformed using dichotomous cutoffs.
3. Results
Twenty neurology and rehabilitation centres throughout Spain participated in this registry between April 2015 and June 2016. The study included 144 patients out of the target sample size of 280 and was terminated due to a slower than expected recruitment rate. Nonetheless, as this is an observational cohort study, the study team proceeded with the planned analyses. Thirteen patients were excluded from this analysis for various reasons, and analyses were performed on the remaining 131 patients (Figure 1). Main baseline characteristics of the study cohort are reported in Table 1. Mean age was , with 49.2% women, and 64.3% of patients being married.
... Non-serious adverse effects include nausea and vomiting [16]. Ghandehari et al. [17] reported no serious adverse effects of MLC601; headache was the only non-serious adverse effect. Mild abdominal discomfort was reported by two patients after receiving MLC601. ...
Background: MLC601 is a natural product formulation from Chinese medicine that is extensively studied in ischemic stroke. Traumatic brain injury (TBI) shares pathophysiological mechanisms with ischemic stroke, yet there are few studies on the use of MLC601 in treating TBI. This Indonesian pilot study aimed to investigate clinical outcomes of MLC601 for TBI. Methods: This randomized controlled trial included subjects with nonsurgical moderate TBI allocated into two groups: with and without MLC601 over three months in addition to standard TBI treatment. Clinical outcomes were measured by the Glasgow Outcome Scale (GOS) and Barthel Index (BI) observed upon discharge and at months (M) 3 and 6. Results: Thirty-two subjects were included. The MLC601 group (n = 16) had higher GOS than the control group (n = 16) at all observation timepoints, though these differences were not statistically significant (p = 0.151). The BI values indicated a significant improvement for the MLC601 group compared to the control group at M3 (47.5 vs. 35.0; p = 0.014) and at M6 (67.5 vs. 57.5; p = 0.055). No adverse effects were associated with MLC601 treatment. Conclusion: In this cohort of nonsurgical moderate TBI subjects, MLC601 showed potential for a positive effect on clinical outcome with no adverse effects.
... A study on recovery of post-stroke visual field deficit [15] randomized 40 patients with homonymous hemianopia from posterior cerebral artery infarction treated for 3 months with either NeuroAiD TM (n=20) or piracetam (n=20). A significant reduction in the measured area of deficits in both eyes was observed for each treatment group (P<.001). ...
... MLC601 (NeuroAiD TM ), a natural product that combines herbal extracts and non-herbal components in the capsule form, demonstrated both neuroprotective and neurorestorative properties in preclinical models of focal and global ischemia [4][5][6] . Clinical studies, which assessed the benefit and safety of MLC601 in non-acute stroke patients using different clinical outcomes [7][8][9][10][11][12][13][14][15][16], have been published. ...
The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years.
All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points.
CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups.
While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke. © 2015 S. Karger AG, Basel.
... Subsequently, the infarct surface area was manually calculated, based on square millimeter. 7,8 Size of venous infarctions was categorized as ≥ 1/3 and ≥ 2/3 of cerebral hemisphere. ...
Anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis (CVT). However, fear of hemorrhagic complications and deterioration course following anticoagulation often disturbs the responsible physician.
This was a Prospective observational study on consecutive CVT patients with hemorrhagic venous infarction or subarachnoid hemorrhage (SAH) admitted in Ghaem Hospital, Mashhad, Iran, during 2006-2012. The diagnosis of CVT in suspected cases was confirmed by magnetic resonance imaging/magnetic resonance venography (MRI/MRV), and computerized tomography (CT) angiography following established diagnostic criteria. Demographic data, clinical manifestations from onset to end of the observation period, location of thrombus, location and size of infarction and hemorrhage, and clinical course during treatment were recorded. Choice of the treatment was left to the opinion of the treating physician. Clinical course during 1 week of treatment was assessed based on the baseline modified National Institute of Health Stroke Scale (NIHSS) score. Three or more points decrease or increase of modified NIHSS after 1 week of treatment was considered as improvement or deterioration courses, respectively. Other clinical courses were categorized as stabilization course.
102 hemorrhagic CVT patients (80 females, 22 males) with mean age of 38.6 ± 8 years were prospectively investigated. Of the 102 hemorrhagic CVT patients in the acute phase, 52 patients (50.9%) were anticoagulated with adjusted dose intravenous heparin infusion and 50 cases (49.1%) received subcutaneous enoxaparin 1mg/Kg twice daily. Decreased consciousness had a significant effect on the clinical course of the patients (X(2) = 9.493, df = 2, P = 0.009). Presence of SAH had no significant effect on the clinical course of our anticoagulated hemorrhagic CVT cases (X(2) = 0.304, df = 2, P = 0.914). Extension of Infarction in more than two thirds of a hemisphere had a significant influence on the distribution of clinical courses (X(2) = 5.867, df = 2, P = 0.044). Difference in distribution of clinical course among the two groups of our hemorrhagic CVT patients was not significant (X(2) = 8.14, df = 1, P = 0.87).
Patients with hemorrhagic CVT without other contraindication for anticoagulation should be treated either with dose-adjusted intravenous heparin or body-weight-adjusted subcutaneous low molecular-weight heparin.
Introduction NeuroAiD, also known as MLC601 or MLC901, is a Chinese herbal combination used worldwide for stroke treatment. It contains herbal components and five hewan components. MLC601 contains herbal components and hewan components, while MLC901 has a similar herbal composition. NeuroAiD is used to support neurologic recovery after stroke and to aid cognitive function in Alzheimer’s disease. Studies show that NeuroAiD has potential in treating Alzheimer’s disease and is beneficial in both local and global stroke models and in the Kortikal culture. However, there is limited bibliometric research on NeuroAiD, which is a method of collecting data from published articles to analyze developments and trends in the field of research. This research contributes significantly to the literature and helps develop more effective stroke treatment strategies. Methods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroaid. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis Results The research trend found are documents by year, most relevant sources, factorial map of the most cited documents, factorial map of The documents with the highest contributes, documents by author, documents by country or territory, documents by subject area, documents by affiliation, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, topic dendogram, and world cloud. Conclusions The study investigates the potential of Neuroaid, a neuroprotective drug, for stroke prevention and cognitive function enhancement. It uses terms like “cognition” and “neurogenesis” to highlight its potential. While the study’s focus may be limited, it provides valuable insights into research direction and potential areas of neuroaid for stroke treatment.
Ethnopharmacological relevance:
Eupolyphaga sinensis Walker (ES) is an insect widely used in traditional East Asian medicine known to exhibit clinical effects on various pathological conditions. Overall, ES is a useful medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required.
Aim of the study:
We aimed to evaluate the current research landscape and diseases associated with ES to synthesize the clinical value of ES based on the associated diseases and underlying therapeutic mechanisms.
Materials and methods:
Embase and PubMed databases were searched for experimental studies that evaluated the therapeutic efficacy or underlying mechanisms of ES until May 2021. The evidence for each study was summarized using a narrative synthesis approach. Studies on extracted or dried whole ES and ES-derived compounds were quantitatively analyzed by year and disease type. Meanwhile, the overall research trend was confirmed for studies on ES-containing prescriptions by visualizing the disease type analysis.
Results:
A total of 151 studies were identified, of which 51 were included in our review. There were 14 studies on extracted or dried whole ES, 15 on ES-derived compounds, and 22 on ES-containing prescriptions. ES was most commonly used for cancer-related diseases, followed by those related to endocrine function and immunity. ES regulates the cell cycle, tumor suppressor genes and proteins, immune-related biomarkers, and antioxidant molecules.
Conclusions:
Overall, ES is a beneficial medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required.
Introduction:
Traumatic brain injury (TBI) is a leading cause of death in young adults globally and 90% of cases are mild TBI. Treatment to facilitate recovery after TBI is needed. Traditional medicine MLC901 (NeuroAiD II) with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury showed TBI-associated cognitive improvement in mild or moderate TBI.
Methods and analysis:
This is a randomised placebo-controlled trial, with 6-month treatment and 9-month follow-up, to determine the safety and efficacy of MLC901 in improving cognitive function in patients with cognitive impairment following mild TBI. This multicentre trial is conducted at the research centres of six hospitals/institutions in Russia. The primary outcome is to determine the effect of MLC901 on complex attention using the CNS Vital Signs (CNS-VS) online neurological test after 6-month treatment in patients receiving MLC901 compared with placebo. Secondary outcomes include other cognitive domains of CNS-VS and Rivermead Post Concussion Symptoms Questionnaire. The exploratory endpoints include Quality of Life after Brain Injury, Hospital Anxiety and Depression Scale and evaluation of improved neurological parameters 3 months after treatment completion. In addition, treatment compliance, concomitant therapies and adverse events will be collected. Investigators will use a secured online system for data entry.
Ethics and dissemination:
The study has been approved by the ethic committee of Ministry of Health of the Russian Federation (No: 58074). The results of this study will be published in a peer-review journal and presented at international conferences as poster presentations.
Trial registration number:
NCT04861688.
Background:
Visual field defects are estimated to affect 20% to 57% of people who have had a stroke. Visual field defects can affect functional ability in activities of daily living (commonly affecting mobility, reading and driving), quality of life, ability to participate in rehabilitation, and depression and anxiety following stroke. There are many interventions for visual field defects, which are proposed to work by restoring the visual field (restitution); compensating for the visual field defect by changing behaviour or activity (compensation); substituting for the visual field defect by using a device or extraneous modification (substitution); or ensuring appropriate diagnosis, referral and treatment prescription through standardised assessment or screening, or both.
Objectives:
To determine the effects of interventions for people with visual field defects after stroke.
Search methods:
We searched the Cochrane Stroke Group Trials Register, the Cochrane Eyes and Vision Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, PsycINFO, and PDQT Databse, and clinical trials databases, including ClinicalTrials.gov and WHO Clinical Trials Registry, to May 2018. We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts.
Selection criteria:
Randomised trials in adults after stroke, where the intervention was specifically targeted at improving the visual field defect or improving the ability of the participant to cope with the visual field loss. The primary outcome was functional ability in activities of daily living and secondary outcomes included functional ability in extended activities of daily living, reading ability, visual field measures, balance, falls, depression and anxiety, discharge destination or residence after stroke, quality of life and social isolation, visual scanning, adverse events, and death.
Data collection and analysis:
Two review authors independently screened abstracts, extracted data and appraised trials. We undertook an assessment of methodological quality for allocation concealment, blinding of outcome assessors, method of dealing with missing data, and other potential sources of bias. We assessed the quality of evidence for each outcome using the GRADE approach.
Main results:
Twenty studies (732 randomised participants, with data for 547 participants with stroke) met the inclusion criteria for this review. However, only 10 of these studies compared the effect of an intervention with a placebo, control, or no treatment group, and eight had data which could be included in meta-analyses. Only two of these eight studies presented data relating to our primary outcome of functional abilities in activities of daily living. One study reported evidence relating to adverse events.Three studies (88 participants) compared a restitutive intervention with a control, but data were only available for one study (19 participants). There was very low-quality evidence that visual restitution therapy had no effect on visual field outcomes, and a statistically significant effect on quality of life, but limitations with these data mean that there is insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control.Four studies (193 participants) compared the effect of scanning (compensatory) training with a control or placebo intervention. There was low-quality evidence that scanning training was more beneficial than control or placebo on quality of life, measured using the Visual Function Questionnaire (VFQ-25) (two studies, 96 participants, mean difference (MD) 9.36, 95% confidence interval (CI) 3.10 to 15.62). However, there was low or very-low quality evidence of no effect on measures of visual field, extended activities of daily living, reading, and scanning ability. There was low-quality evidence of no significant increase in adverse events in people doing scanning training, as compared to no treatment.Three studies (166 participants) compared a substitutive intervention (a type of prism) with a control. There was low or very-low quality evidence that prisms did not have an effect on measures of activities of daily living, extended activities of daily living, reading, falls, or quality of life, and very low-quality evidence that they may have an effect on scanning ability (one study, 39 participants, MD 9.80, 95% CI 1.91 to 17.69). There was low-quality evidence of an increased odds of an adverse event (primarily headache) in people wearing prisms, as compared to no treatment.One study (39 participants) compared the effect of assessment by an orthoptist to standard care (no assessment) and found very low-quality evidence that there was no effect on measures of activities of daily living.Due to the quality and quantity of evidence, we remain uncertain about the benefits of assessment interventions.
Authors' conclusions:
There is a lack of evidence relating to the effect of interventions on our primary outcome of functional ability in activities of daily living. There is limited low-quality evidence that compensatory scanning training may be more beneficial than placebo or control at improving quality of life, but not other outcomes. There is insufficient evidence to reach any generalised conclusions about the effect of restitutive interventions or substitutive interventions (prisms) as compared to placebo, control, or no treatment. There is low-quality evidence that prisms may cause minor adverse events.
Cardiac arrest and traumatic brain injury are a socio economic health problem. Despite lot of hopes on neuroprotective therapies, few confirmed promising experimental results in clinical studies. Traditional Chinese Medicine has been used for several centuries. Despite lot of clinical investigations, few data are available on mechanisms involved in their effects. Interesting results have been published in stroke patients, and experimental studies using MLC601 and MLC901 have been conducted in mouse focal ischemia models. The multiple mechanisms of action, neuroprotective and neuroregenerative, of these treatments have been highlighted. The purpose of our study was to analyse the neuroprotective and neuroregenerative actions of MLC901 on rat global ischemia and traumatic brain injury models. In these models, we confirmed the neuroprotective action on necrosis, apoptosis and oxidative stress and the neuroregenerative action by the way of neurogenesis activation. These cellular actions are associated with functional recovery in the two models. We confirmed in these two experimental models, the neuroprotective and neuroregenerative effects of MLC901 on post ischemic or post traumatic brain injuries. This approach is essential for Traditional Chinese Medicine to be accepted by occidental one.
Background:
Subsequent to a pooled analysis of 2 trials, several more studies have been published assessing the benefit of MLC601 in stroke patients. Hence, it is timely to conduct an updated meta-analysis to frame the interpretation of the results of an ongoing large multicenter, randomized, double-blind, placebo-controlled study. Therefore, we conducted a systematic review of the efficacy of MLC601 in improving the recovery of stroke patients.
Methods:
PubMed® and the Cochrane Library® databases were searched for trials evaluating MLC601 in stroke patients. Primary outcome was functional independence, assessed by the Barthel Index or the Diagnostic Therapeutic Effects of Apoplexy scoring system, item 8. Secondary outcomes were improvement in functional independence scores, motor recovery, reduction in visual field defect and increase in cerebral blood flow. Two authors performed the article selection, appraisal and data extraction while resolving differences through discussion or consulting a third author. Data were analyzed in RevMan5®. Meta-analysis was conducted using a random effects model.
Results:
This review included 6 studies with overall low risk of bias but some clinical heterogeneity. MLC601 increased the chances of achieving functional independence after stroke compared to control treatments (risk ratio, 2.35; 95% CI, 1.31-4.23). No deaths and 4 serious adverse events were reported in the MLC601 group, although detail was sparse with inconsistent reporting.
Conclusions:
There is evidence that MLC601 as an add-on to standard treatment could be effective in improving functional independence and motor recovery and is safe for patients with primarily nonacute stable stroke.
Rationale:
The clinical effects of neuroprotective and/or neurorestorative therapies may vary according to location and size of the ischemic injury. Imaging techniques can be useful in stratifying patients for trials that may be beneficial against particular ischemic lesion characteristics.
Aim:
To test the hypothesis that the efficacy of NeuroAiD compared with placebo in improving functional outcome and reducing neurological deficit in patients with cerebral infarction of intermediate severity varies between sub-groups of patients randomized in the main Chinese Medicine Neuroaid Efficacy on Stroke study when categorized according to baseline imaging characteristics.
Design:
This is a retrospective cohort sub-group analysis of patients who participated in the main Chinese Medicine Neuroaid Efficacy on Stroke study, a multicenter, double-blind, placebo-controlled trial that recruited 1100 patients within 72 h of ischemic stroke onset with National Institutes of Health Stroke Scale 6-14 and were randomized to either NeuroAiD or placebo taken four capsules three times daily for three months. Review of the baseline images to classify the acute stroke lesions in terms of size, location, and extent of involvement will be performed retrospectively by two readers who will remain blinded as to treatment allocation and outcomes of the subjects.
Study outcomes:
The primary efficacy end-point in the main Chinese Medicine Neuroaid Efficacy on Stroke study is the modified Rankin Scale grades at three-months. Secondary efficacy end-points are the National Institutes of Health Stroke Scale score at three-months; difference of National Institutes of Health Stroke Scale scores between baseline and 10 days and between baseline and three-months; difference of National Institutes of Health Stroke Scale sub-scores between baseline and 10 days and between baseline and three-months; modified Rankin Scale at 10 days, one-month, and three-months; Barthel index at three-months; and Mini Mental State Examination at 10 days and three-months. Analysis of these primary and secondary end-points will be performed for sub-groups defined in this study after review of the baseline brain imaging: nonlacunar and lacunar, cortical and sub-cortical, hemispheric vs. brainstem, Alberta Stroke Program Early CT score <7 and 7-10, and score <8 and 8-10.
Rationale Traditional Chinese Medications(TCM) have been reported to have beneficial effects in stroke patients, but were not rigorously evaluated by GCP standards.
Aim This study tests the hypothesis that Neuroaid, a TCM widely used in China post-stroke, is superior to placebo in reducing neurological deficit and improving functional outcome in patients with acute cerebral infarction of an intermediate severity.
Design This is a multicenter, randomised, double-blind, placebo-controlled study of Neuroaid in ischemic stroke patients with National Institute of Health Stroke Scale(NIHSS) 6–14 treated within 48 h of stroke onset. Neuroaid or placebo is taken (4 capsules) 3 times daily for 3 months. Treatments are assigned using block randomization, stratified for centers, via a central web-randomization system. With a power of 90% and two-sided test of 5% type I error, a sample size is 874. Allowing for a drop-out rate of up to 20%, 1100 individuals should be enrolled in this study.
Study Outcomes The primary efficacy endpoint is the modified Rankin Scale(mRS) grades at 3 months. Secondary efficacy endpoints are the NIHSS score at 3 months; difference of NIHSS scores between baseline and 10 days, and between baseline and 3 months; difference of NIHSS sub-scores between baseline and 10 days, and between baseline and 3 months; mRS at 10 days, 1 month, and 3 months; Barthel index at 3 months; Mini Mental State Examination at 10 days and 3 months. Safety outcomes include complete blood count, renal and liver panels, and electrocardiogram.
Study registration: ClinicalTrials.gov identifier: NCT00554723.
Stroke is a leading cause of death and disability worldwide. Despite improvements in acute stroke treatment, many patients only make a partial or poor recovery. Therefore, there is a need for treatments that would further improve outcome. Danqi Piantang Jiaonang (DJ; NeuroAid), a traditional Chinese medicine widely used in China to improve recovery after stroke, has been compared with another traditional Chinese medicine in 2 unpublished randomized clinical trials. The results of these studies were pooled and reanalyzed to assess efficacy and safety.
Six hundred five subjects were randomized in 2 randomized double-blinded, controlled trials to receive either DJ or Buchang Naoxintong Jiaonang. Subjects were treated for 1 month. Inclusion criteria were: (1) patients with recent (from 10 days to 6 months) ischemic stroke; (2) patients satisfying Western diagnostic standards for stroke and traditional Chinese medicine standards for diagnosis of apoplexy; and (3) Diagnostic Therapeutic Effects of Apoplexy score >/=10.
The functional outcome, measured by the Comprehensive Function Score component of the Diagnostic Therapeutic Effects of Apoplexy scale, showed a statistically significant superiority of DJ over the control treatment group (relative risk, 2.4; 95% CI, 1.28 to 4.51; P=0.007). Tolerance was excellent in both groups.
The pooled analysis of 2 unpublished trials of DJ, a traditional Chinese medicine currently approved in China to improve neurological recovery after stroke, shows good tolerability and superiority of DJ over another traditional Chinese medicine also approved for stroke. A large double-blind randomized clinical trial is required to further assess the safety and efficacy of DJ.
Background and Purpose Piracetam, a nootropic agent with neuroprotective properties, has been reported in pilot studies to increase compromised regional cerebral blood flow in patients with acute stroke and, given soon after onset, to improve clinical outcome. We performed a multicenter, randomized, double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients.
Methods Patients received placebo or 12 g piracetam as an initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g daily for 8 weeks. The primary end point was neurologic outcome after 4 weeks as assessed by the Orgogozo scale. Functional status at 12 weeks as measured by the Barthel Index was the major secondary outcome. CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment. Analyses based on the intention to treat were performed in all randomized patients (n=927) and in an “early treatment” population specified in the protocol as treatment within 6 hours of the onset of stroke but subsequently redefined as less than 7 hours after onset (n=452).
Results In the total population, outcome was similar with both treatments (the mean Orgogozo scale after 4 weeks: piracetam 57.7, placebo 57.6; the mean Barthel Index after 12 weeks: piracetam 55.8, placebo 53.1). Mortality at 12 weeks was 23.9% (111/464) in the piracetam group and 19.2% (89/463) in the placebo group (relative risk 1.24, 95% confidence interval, 0.97 to 1.59; P =.15). Deaths were fewer in the piracetam group in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke. Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo scale scores after 4 weeks (piracetam 60.4, placebo 54.9; P =.07) and Barthel Index scores at 12 weeks (piracetam 58.6, placebo 49.4; P =.02). Additional analyses within this subgroup, confined to 360 patients with moderate and severe stroke (initial Orgogozo scale score <55), showed significant improvement on piracetam in both outcomes ( P <.02).
Conclusions Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Post hoc analyses suggest that piracetam may confer benefit when given within 7 hours of onset, particularly in patients with stroke of moderate and severe degree. A randomized, placebo-controlled, multicenter study, the Piracetam Acute Stroke Study II (PASS II) will soon begin.
Previous clinical studies have shown that Neuroaid (MLC 601) may be beneficial in post-stroke rehabilitation. Our aim was to investigate the efficacy of Neuroaid on motor recovery in ischemic stroke patients using rehabilitation endpoints in accordance with the International Conference on Harmonization/Good Clinical Practice guidelines, in order to provide predictive information for further larger trials.
This is a phase II double-blind, placebo-controlled pilot study of 40 subjects admitted with a recent (less than 1 month) ischemic stroke. All subjects were given either Neuroaid or placebo, 4 capsules 3 times a day for 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale and Functional Independence Measure scores were measured at initiation of the treatment, and at 4 and 8 weeks.
None of the outcomes was statistically significant between the two groups. However, FMA scores showed a positive trend for improvement with Neuroaid treatment over time. Subgroup analysis of subjects with posterior circulation infarction and severe stroke both showed a tendency for better recovery.
Some positive trends were observed in the Neuroaid group. A larger multicenter trial focusing on severe stroke patients is needed to better evaluate the role of Neuroaid in aiding stroke recovery in rehabilitation.
Sorry, there is no abstract. Read the first few lines of the text instead!
We studied whether the administration of piracetam in acute, presumed ischemic stroke affects case fatality and functional outcome. The Cochrane Stroke Group strategy was used to evaluate all randomized controlled trials of patients with presumed ischemic stroke examined within 48 h; death and (when available) functional outcome were used as end points. Three studies were included; the most recent one contributed more than 97% of the data. There were 501 patients treated with piracetam and 501 controls. Piracetam was associated with a nonsignificant 31% increase in the odds of death (95% CI -5% to 81%). This result was due almost completely to the effect of the larger trial, which, however, reported that the difference in case fatality rate between piracetam and control disappeared after correcting for the imbalance in stroke severity between the two groups. Data on functional outcome were available only for the largest study, and no difference was reported. Data obtained from the manufacturer suggested a nonsignificant trend (-10%) towards reduction in dependency with piracetam (CI -33% to 20%); the proportions of patients dead or dependent in the two groups were the same. Relevant adverse effects were not reported. The evidence from this review does not support routine administration of piracetam in patients with acute ischemic stroke; however, since a possible beneficial effect cannot completely be ruled out, further controlled trials are warranted.