Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema.

BACKGROUND: Upper airway angioedema is a rare, unpredictable, and at times life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACE-Is) with no existing effective pharmacologic treatment. Icatibant is a bradykinin B2 receptor antagonist that may be beneficial in patients with ACE-I-induced angioedema.

OBJECTIVE: We aimed to evaluate the efficacy of icatibant in subjects with ACE-I-induced angioedema.

METHODS: At 31 centers in 4 countries, adults on ACE-Is who presented within 12 hours of the onset of at least moderately severe angioedema were randomized 1:1 to icatibant 30 mg or placebo administered subcutaneously. The primary efficacy end point was time to meeting discharge criteria after study drug administration, based on the severity of airway symptoms assessed hourly by a blinded physician using clinical ratings across 4 domains.

RESULTS: A total of 121 subjects were randomized (icatibant, n = 61; placebo, n = 60); 118 received treatment a median of 7.8 hours from symptom onset. We observed no difference in time to meeting discharge criteria between groups (median, 4.0 hours in each group; P = .63). There also was no difference in time to onset of symptom relief (median, icatibant, 2.0 hours; placebo, 1.6 hours; P = .57) or any other secondary end point. Similar findings were noted in prespecified and post hoc subgroup analyses stratified by symptom severity, time interval to treatment, age, and other clinical covariates. No new safety signals were detected.

CONCLUSIONS: Icatibant was no more efficacious than placebo in at least moderately severe ACE-I-induced angioedema of the upper airway.