Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks
ABSTRACT Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder.
To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema.
This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours.
Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus.
C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief.
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- "Therapeutic administration of C1-inh is clinically applied in the context of hereditary angioedema (HAE), which is hallmarked by heterozygous C1-inh deficiency (Donaldson & Evans, 1963). Randomized controlled trials in patients demonstrated that C1-inh administration effectively decreased the severity of HAE-episodes, without having serious side-effects (Kunschak et al., 1998; Craig et al., 2009). "
ABSTRACT: Abstract Context: C1-esterase inhibitor (C1-inh) therapy is currently administered to patients with C1-inh deficiency through intravenous injections. The possibility of subcutaneous administration is currently being explored since this would alleviate need for hospitalization and increase mobility and well-being of patients. Recently, it was observed in pigs that C1-inh indeed can effectively be applied by subcutaneous injection. For studies on the effectiveness of C1-inh therapy for other indications than acquired and hereditary angioedema, rats are commonly used as model animal. For rats, however, subcutaneous C1-inh administration has never been investigated. Objective: To evaluate the efficacy of subcutaneous C1-inh administration in rats. Materials and methods: Three boli of 100 U/kg human plasma-derived C1-inh were administered to Wistar rats on three consecutive days through subcutaneous injection or intravenous injection. Blood samples were collected from the tail veins 3, 4.5 or 6 h after C1-inh administration for measurement of C1-inh plasma levels. Antigen and activity levels of C1-inh of each plasma sample were determined by means of a specific ELISA. Results: For both C1-inh antigen and C1-inh activity, 21- to 119-fold higher plasma levels were measured after intravenous administration compared with subcutaneous administration. Subcutaneous administration also resulted in C1-inh plasma levels that were less stable and with decreased relative activity. Conclusion: These combined results indicate that in rats, subcutaneous injections in the present formulation are not effective as alternative administration route for C1-inh.Drug Delivery 11/2013; DOI:10.3109/10717544.2013.853211 · 2.20 Impact Factor
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ABSTRACT: The Critical Path based Project Management tools do not take an adequate account of risk. Monte Carlo Simulation provides an improved methodology to quantify schedule risk, and as such is a significant advance in project management technology. This paper illustrates the use of this methodology for better understanding, designing, and managing a project such that the detrimental effects of these risks can be minimized. In addition, the results of this methodology are contrasted with that of CPM, PERT, and PROBABILISTIC PERT. This contrast illustrates the shortcomings of these widely used methodologies in a typical Engineering environment.Robotics and Automation. Proceedings. 1986 IEEE International Conference on; 05/1986
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ABSTRACT: Hysteresis effects of annular flow in rotating stepped wall heat pipes are addressed based on visualization and systematic experiments. The region of hysteretic annular flow is defined. Experimental data for the annular flow condensation heat transfer in a rotating stepped wall heat pipe are presented. A model for predicting the condensation heat transfer coefficient is proposed. The theoretical results are compared with experimental data. The effect of vapor shear drag on the condensation heat transfer is discussedEnergy Conversion Engineering Conference, 1997. IECEC-97., Proceedings of the 32nd Intersociety; 01/1997