Lawrence M Lewis1, Charles Graffeo2, Pascal Crosley3, Howard A Klausner4, Carol L Clark5, Anthony Frank6, James Miner7, Ryan Iarrobino8, Yung Chyung8. 1. Washington University School of Medicine, St. Louis, MO. Electronic address: lewisl@wusm.wustl.edu. 2. Eastern Virginia Medical School, Norfolk, VA. 3. DeKalb Medical Center, Decatur, GA. 4. Henry Ford Health System, Detroit, MI. 5. William Beaumont Hospital, Royal Oak, MI. 6. East Carolina University, Greenville, NC. 7. Hennepin County Medical Center, Minneapolis, MN. 8. Dyax Corp, Burlington, MA.
Abstract
STUDY OBJECTIVE: We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED). METHODS: This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration. Discharge criteria included improvement of edema, stable vital signs, absence of stridor, absence of dyspnea or use of accessory muscles during respiration, absence of drooling, and ability to drink without difficulty. RESULTS: An interim analysis showed that a high percentage of subjects met the primary endpoint, and the study was halted. Overall, 79 subjects were randomized and 76 had data for analysis. Most had mild (45%) or moderate (42%) ACEIA. The discharge eligibility endpoint was met by 72% of the placebo group and 85%, 89%, and 89% of the ecallantide 10-, 30-, and 60-mg groups, respectively. This difference in meeting discharge eligibility endpoint criteria between treatment groups was not statistically significant. The incidence of treatment-emergent adverse events was similar between placebo and active-treatment groups. CONCLUSION: The addition of ecallantide to standard therapy does not appear to improve angioedema compared with placebo in ED patients with ACEIA. Our data suggest that most ED patients presenting with mild to moderate ACEIA are likely to meet our discharge eligibility criteria within 6 hours of treatment, regardless of intervention. Further studies to assess the utility of ecallantide in patients with more severe angioedema may be useful. No new safety signals related to ecallantide administration were identified.
RCT Entities:
STUDY OBJECTIVE: We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED). METHODS: This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration. Discharge criteria included improvement of edema, stable vital signs, absence of stridor, absence of dyspnea or use of accessory muscles during respiration, absence of drooling, and ability to drink without difficulty. RESULTS: An interim analysis showed that a high percentage of subjects met the primary endpoint, and the study was halted. Overall, 79 subjects were randomized and 76 had data for analysis. Most had mild (45%) or moderate (42%) ACEIA. The discharge eligibility endpoint was met by 72% of the placebo group and 85%, 89%, and 89% of the ecallantide 10-, 30-, and 60-mg groups, respectively. This difference in meeting discharge eligibility endpoint criteria between treatment groups was not statistically significant. The incidence of treatment-emergent adverse events was similar between placebo and active-treatment groups. CONCLUSION: The addition of ecallantide to standard therapy does not appear to improve angioedema compared with placebo in ED patients with ACEIA. Our data suggest that most ED patients presenting with mild to moderate ACEIA are likely to meet our discharge eligibility criteria within 6 hours of treatment, regardless of intervention. Further studies to assess the utility of ecallantide in patients with more severe angioedema may be useful. No new safety signals related to ecallantide administration were identified.
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