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Activities supporting the growth of Clinical Trial Networks in Australia

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Activities supporting the growth of Clinical Trial Networks in Australia

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Abstract

Clinical Trial Networks in which trialists work collaboratively enable multi-site, large-scale, high-quality clinical trials to be efficiently run. Although the benefits of Clinical Trial Networks are largely known, establishing a Clinical Trial Network can be complex. There are many factors for clinicians and researchers to consider, and there is currently a paucity of information on how to form a Clinical Trial Network. This article provides a suggested roadmap on how to establish a Clinical Trial Network. The Australian Clinical Trials Alliance (ACTA) is the peak body for Clinical Trial Networks, Coordinating Centres and Registries in Australia, and has produced several resources to support the effective and efficient running of clinical trials. This guide has come about through discussions with members of the ACTA Clinical Trial Network Sector Expansion Reference Group consisting of clinical trialists, clinicians, researchers, and consumers.

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... Clinical research networks within other specialty societies have proved effective in setting research priorities, promoting research collaborations and providing research training. [2][3][4][5][6] Such networks have facilitated large multicentre studies by bringing together like-minded researchers with clinical expertise and knowledge, providing a forum to advertise and share projects aligned with identified priorities, and attracting funding through advocacy. 5,6 Publications in high-impact journals and dissemination of results through local and international collaborations has led to changes in clinical guidelines and ultimately clinical practice. ...
... [2][3][4][5][6] Such networks have facilitated large multicentre studies by bringing together like-minded researchers with clinical expertise and knowledge, providing a forum to advertise and share projects aligned with identified priorities, and attracting funding through advocacy. 5,6 Publications in high-impact journals and dissemination of results through local and international collaborations has led to changes in clinical guidelines and ultimately clinical practice. 7,8 Developing a similar research network under the auspices of IMSANZ is seen as a means for accelerating robust, collaborative research activities among general physicians that identify and address specific needs of the community, patients and health services. ...
... Clinical research networks have been shown to be effective models in conducting large-scale clinical, epidemiology and health service research. 5 Through a collaborative framework, these networks define discipline-specific research agendas and priorities, develop research questions relevant to the patient populations of interest, and identify research methodologies that are applicable in answering these questions. 5,6,11 Additionally, they promote research culture, enable exchange of ideas, provide formal and informal networking opportunities to established researchers, as well as to clinicians interested in pursuing a research career. ...
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Background: In developing an effective framework for a collaborative research network (RN) that supports members involved in research, the Internal Medicine Society of Australia and New Zealand (IMSANZ) required a better understanding of the current level of research activity and engagement by general physicians, and factors influencing such engagement. Methods: A questionnaire exploring research participation, scope, research enablers and barriers was disseminated to IMSANZ members over a three-month period. Core functions of IMSANZ-RN, research priorities, potential solutions to perceived barriers and required level of support were also evaluated. Results: A total of 82 members, mostly senior medical staff (74.4%), responded to the survey (11.8% response rate). More than 70% were involved in impactful research across multiple disciplines, encompassing a wide range of research themes and topics. However, there is limited support and resources available to conduct research, with most projects being self-instigated and self-funded. There is overwhelming support to increasing the profile of research in general medicine through the establishment of IMSANZ-RN whose principal purposes, as identified by respondents, are to foster collaboration, promote research, provide research education and training, and share information among general physicians. Quality improvement studies (56.1%) and clinical trials (41.5%) were also identified as priority research types. Conclusions: This study has profiled the constraints faced by general physicians in conducting high quality collaborative research and provides insights into what is needed to support greater research engagement, through development of a discipline-specific clinical research network. This article is protected by copyright. All rights reserved.
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The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.
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Objectives To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial design ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. Intervention and comparator Participants will be randomised 1:1:1:1 to: Group 1 : standard of care; Group 2 : lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3 : hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4 : lopinavir /ritonavir plus hydroxychloroquine. Main outcomes Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. Randomisation The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. Blinding (masking) This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. Numbers to be randomised (sample size) We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. Trial Status ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia (CAP). The trial uses a novel design entitled a randomized embedded multifactorial adaptive platform (REMAP). The design has 5 key features: i.) randomization, allowing robust causal inference; ii.) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; iii.) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; iv.) response-adaptive randomization with preferential assignment to those interventions that appear most favorable, and v.) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within 4 treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP was approved and enrolling patients in 52 ICUs in 13 countries in 3 continents. In February, it transitioned into pandemic mode with several design adaptations for COVID-19 disease. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas. Clinical trial registered with ClinicalTrials.gov (NCT02735707).
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Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed. Electronic supplementary material The online version of this article (doi:10.1186/s40697-015-0080-7) contains supplementary material, which is available to authorized users.
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Background: Acetaminophen is a common therapy for fever in patients in the intensive care unit (ICU) who have probable infection, but its effects are unknown. Methods: We randomly assigned 700 ICU patients with fever (body temperature, ≥38°C) and known or suspected infection to receive either 1 g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, cessation of antimicrobial therapy, or death. The primary outcome was ICU-free days (days alive and free from the need for intensive care) from randomization to day 28. Results: The number of ICU-free days to day 28 did not differ significantly between the acetaminophen group and the placebo group: 23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen and 22 days (interquartile range, 12 to 25) among patients assigned to placebo (Hodges-Lehmann estimate of absolute difference, 0 days; 96.2% confidence interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%) had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84). Conclusions: Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819.).
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Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions.Kidney International advance online publication, 2 October 2013; doi:10.1038/ki.2013.391.
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Within many health care disciplines, research networks have emerged to connect researchers who are physically separated, to facilitate sharing of expertise and resources, and to exchange valuable skills. A multicentre research network committed to studying difficult cancer pain problems was launched in 2004 as part of a Canadian initiative to increase palliative and end-of-life care research capacity. Funding was received for 5 years to support network activities. Mid-way through the 5-year granting period, an external review panel provided a formal mid-grant evaluation. Concurrently, an internal evaluation of the network by survey of its members was conducted. Based on feedback from both evaluations and on a review of the literature, we identified several components believed to be relevant to the development of a successful clinical cancer research network. THESE COMMON ELEMENTS OF SUCCESSFUL CLINICAL CANCER RESEARCH NETWORKS WERE IDENTIFIED: shared vision, formal governance policies and terms of reference, infrastructure support, regular and effective communication, an accountability framework, a succession planning strategy to address membership change over time, multiple strategies to engage network members, regular review of goals and timelines, and a balance between structure and creativity. In establishing and conducting a multi-year, multicentre clinical cancer research network, network members were led to reflect on the factors that contributed most to the achievement of network goals. Several specific factors were identified that seemed to be highly relevant in promoting success. These observations are presented to foster further discussion on the successful design and operation of research networks.
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Background Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. Methods In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m² of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Results Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m²; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (−3.33 ml per minute per 1.73 m² per year [95% confidence interval {CI}, −4.11 to −2.55] and −3.23 ml per minute per 1.73 m² per year [95% CI, −3.98 to −2.47], respectively; mean difference, −0.10 ml per minute per 1.73 m² per year [95% CI, −1.18 to 0.97]; P=0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. Conclusions In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.)
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The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network was formed to build capacity and infrastructure for high quality musculoskeletal clinical trials in our region. The purpose of this paper is to describe the steps taken in its formation to help others interested in establishing similar networks. In particular we describe the steps taken to form the collaboration and our progress in achieving our vision and mission. Our aim is to focus on trials of highest importance and quality to provide definitive answers to the most pressing questions in our field. This article is protected by copyright. All rights reserved.
Article
Background: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. Methods: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. Results: The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). Conclusions: In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.
Article
Investigator initiated clinical trials are critical to the advancement of cancer care in Australia. Cooperative clinical trials groups in Australia and New Zealand contribute greatly to independent investigator initiated research across a wide spectrum of cancer types and interventions. Achievements of the groups and their contributions to improvement in cancer care over the past 40 years are highlighted. Future challenges in the field of clinical trials are discussed with particular regard to cooperative clinical trials groups.
Article
Despite a substantial contribution to the global burden of disease, musculoskeletal conditions are under-represented in clinical research, and that which is performed is often wasteful and lacking clinical relevance. Even clinically relevant musculoskeletal research might not lead to timely or adequate changes in clinical practice and associated improvements in patient outcomes. The formulation of clinical recommendations alone is usually insufficient to bring about changes in practice patterns. Research exploring how to improve the translation of evidence-based recommendations into practice, as well as the identification and removal of barriers to practice change, is necessary in order for the promise of musculoskeletal research to be realized in improved health outcomes. These goals can be achieved by improvements in the coordination of research activities, the resourcing and allocation of funding, and the involvement of clinicians and patients.
Article
Background: Over the last decade, the United Kingdom has invested significant resources in its clinical trial infrastructure. Clinical research networks have been formed, and some general oversight functions for clinical research have been centralised. One of the initiatives is a registration programme for Clinical Trials Units involved in the coordination of clinical trials. An international review panel of experts in clinical trials has been convened for three reviews over time, reviewing applications from Clinical Trials Units in the United Kingdom. The process benefited from earlier work by the National Cancer Research Institute that developed accreditation procedures for trials units involved in cancer trials. This article describes the experience with the three reviews of UK Clinical Trials Units which submitted applications. Purpose: This article describes the evolution and impact of this registration process from the perspective of the current international review panel members, some of whom have served on all reviews, including two done by the National Cancer Research Institute. Process: Applications for registration were invited from all active, non-commercial Clinical Trials Units in the United Kingdom. The invitations were issued in 2007, 2009 and 2012, and applicants were asked to describe their expertise and staffing levels in specific areas. To ensure that the reviews were as objective as possible, a description of expected core competencies was developed and applicants were asked to document their compliance with meeting these. The review panel assessed each Clinical Trials Unit against the competencies. The Clinical Trials Unit registration process has evolved over time with each successive review benefiting from what was learned in earlier ones. Results: The review panel has seen positive changes over time, including an increase in the number of units applying, a greater awareness on the part of host institutions about the trials activity within their organisations, more widespread development of Standard Operating Procedures in key areas and improvements in information technology systems used to host clinical trials databases. Key funders are awarding funds only to registered units, and host institutions are implementing procedures and structures to ensure improved communication between all parties involved in trials within their organisation. Conclusion: The registration process developed in the United Kingdom has helped to ensure that trials units in the United Kingdom are compliant with regulatory standards and can meet acceptable standards of quality in their conduct of clinical trials. There is an increased awareness among funders, host institutions and Clinical Trials Units themselves of the required competencies, and communication between all those involved in trials has increased. The registration process is an effective and financially viable way of ensuring that objective standards are met at a national level.
Article
To review the significant advances in cancer prevention, detection, treatment, and symptom management among the National Cancer Institute (NCI)-supported clinical trials cooperative groups, the Institute of Medicine (IOM) recommendations for restructuring of the national clinical trials infrastructure, and to discuss the contributions nurses have made in national clinical trials. Published cooperative group manuscripts and NCI data. The NCI-sponsored clinical trials cooperative groups have conducted major evidence-based, practice-changing clinical trials. Despite the advances, challenges in the process of clinical trials have caused the NCI to restructure the clinical trials network to improve efficiencies and decrease time from concept to protocol development to clinical trials completion. Nurse investigators work with the cooperative groups for a number of reasons, including access to a large multisite population of cancer patients, making findings more generalizable. There are also increasing opportunities for areas of research including biomechanistic understanding of symptoms and symptom therapies, survivorship, and cancer care delivery.
Article
Musculoskeletal conditions are the leading contributors to disability burden globally and account for 27.4% of total disability burden in Australia. Timely research that addresses important questions relevant to consumers, clinicians and policymakers is critical for reducing the burden associated with these conditions. Clinical trials are particularly important for providing information about whether interventions are effective and safe. They are also needed to test strategies for reducing the sizeable delays in translating evidence into practice. A review of the current scope of musculoskeletal clinical trials in Australia found that National Health and Medical Research Council funding is disproportionally low compared with the burden of these conditions (averaging 5.8 new trials per year through the project grant scheme over the past 5 years, representing 0.8% of all project grants and funding, and 5% of NHMRC clinical trial funding). In the past 2 years, 128 Australian-initiated trials were registered in a trial registry, while about one in 20 randomised trials published in 37 leading general medical and musculoskeletal-specific journals was initiated in Australia. None were implementation trials. Relative to the burden of musculoskeletal conditions in Australia, investment in clinical trials is not ideal. While Australian musculoskeletal trialists are productive and internationally competitive, we may not be addressing the most critical issues. There is an urgent need for Australian researchers, clinicians, policymakers and consumers to work collaboratively to prioritise the most important questions, secure appropriate research funding, and undertake well designed trials to ensure we deliver best evidence-informed care and optimal outcomes for people with musculoskeletal conditions.
Article
The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer-reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases.
Article
Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised controlled trial, and use of dopamine remains controversial. We have done a multicentre, randomised, double-blind, placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction (oliguria or increase in serum creatinine concentration). 328 patients admitted to 23 participating intensive-care units (ICUs) were randomly assigned a continuous intravenous infusion of low-dose dopamine (2 microg kg(-1) min(-1)) or placebo administered through a central venous catheter while in the ICU. The primary endpoint was the peak serum creatinine concentration during the infusion. Analyses excluded four patients with major protocol violations. The groups assigned dopamine (n=161) and placebo (n=163) were similar in terms of baseline characteristics, renal function, and duration of trial infusion. There was no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment (245 [SD 144] vs 249 [147] micromol/L; p=0.93), in the increase from baseline to highest value during treatment (62 [107] vs 66 [108] micromol/L; p=0.82), or in the numbers of patients whose serum creatinine concentration exceeded 300 micromol/L (56 vs 56; p=0.92) or who required renal replacement therapy (35 vs 40; p=0.55). Durations of ICU stay (13 [14] vs 14 [15] days; p=0.67) and of hospital stay (29 [27] vs 33 [39] days; p=0.29) were also similar. There were 69 deaths in the dopamine group and 66 in the placebo group. Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.
Article
Awareness is an uncommon complication of anaesthesia, affecting 0.1-0.2% of all surgical patients. Bispectral index (BIS) monitoring measures the depth of anaesthesia and facilitates anaesthetic titration. In this trial we determined whether BIS-guided anaesthesia reduced the incidence of awareness during surgery in adults. We did a prospective, randomised, double-blind, multicentre trial. Adult patients at high risk of awareness were randomly allocated to BIS-guided anaesthesia or routine care. Patients were assessed by a blinded observer for awareness at 2-6 h, 24-36 h, and 30 days after surgery. An independent committee, blinded to group identity, assessed every report of awareness. The primary outcome measure was confirmed awareness under anaesthesia at any time. Of 2463 eligible and consenting patients, 1225 were assigned to the BIS group and 1238 to the routine care group. There were two reports of awareness in the BIS-guided group and 11 reports in the routine care group (p=0.022). BIS-guided anaesthesia reduced the risk of awareness by 82% (95% CI 17-98%). BIS-guided anaesthesia reduces the risk of awareness in at-risk adult surgical patients undergoing relaxant general anaesthesia. With a cost of routine BIS monitoring at US16 dollars per use in Australia and a number needed to treat of 138, the cost of preventing one case of awareness in high-risk patients is about 2200 dollars.
Article
Despite some concern that recent aspirin ingestion increases blood loss after coronary artery surgery, there is some evidence that this may reduce thrombotic complications. In contrast, antifibrinolytic drugs can reduce blood loss in this setting, but there is concern that they may increase thrombotic complications. Published guidelines are limited by a lack of large randomized trials addressing the risks and benefits of each of these commonly used therapies in cardiac surgery. The ATACAS Trial is a study comparing aspirin, tranexamic acid, or both, with placebo in patients undergoing on-pump or off-pump coronary artery surgery. We discuss the rationale for conducting ATACAS, a 4600-patient, multicenter randomized trial in at-risk coronary artery surgery, and the features of the ATACAS study design (objectives, end points, target population, allocation, treatments, patient follow-up, and analysis). The ATACAS Trial will be the largest study yet conducted to ascertain the benefits and risks of aspirin and antifibrinolytic therapy in coronary artery surgery. Results of the trial will guide the routine clinical care of patients in this setting.
Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial
  • J R Rigg
  • K Jamrozik
  • P S Myles
  • B S Silbert
  • P J Peyton
  • R W Parsons
  • JR Rigg
Aspirin in coronary artery surgery: 1-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial
  • P S Myles
  • J A Smith
  • J Kasza
  • B Silbert
  • M Jayarajah
  • T Painter
  • PS Myles
Establishing a clinical trials network in nephrology: experience of the Australasian Kidney Trials Network
  • A T Morrish
  • C M Hawley
  • D W Johnson
  • S V Badve
  • V Perkovic
  • D M Reidlinger
  • AT Morrish
Goal-directed resuscitation for patients with early septic shock
  • S L Peake
  • A Delaney
  • M J Bailey
  • R Bellomo
  • P Cameron
  • D J Cooper
  • SL Peake
Tranexamic acid in coronary artery surgery: one-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial
  • P S Myles
  • J A Smith
  • J Kasza
  • B Silbert
  • M Jayarajah
  • T Painter
  • PS Myles
NIH funds follow up observational study ASPREE-XT (eXTension)
  • Aspree
  • Org
Bentum-Puijk Wv, et al. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design
  • DC Angus
  • S Berry
  • RJ Lewis
  • F Al-Beidh
  • Y Arabi