Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema

Study Overview
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Brief Summary
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Individuals with heart disease or high blood pressure are often prescribed angiotensin converting enzyme (ACE) inhibitors to treat their disease. However, the use of ACE inhibitors can be associated with angioedema, a rare but life-threatening condition that causes swelling of the face and other body parts. This study will evaluate the effectiveness of the drug HOE-140 at decreasing symptoms of angioedema in people taking ACE inhibitors who develop the condition.

Detailed Description
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People who take ACE inhibitors may develop angioedema, a condition that causes itchy and painful swelling beneath the skin around the eyes, lips, tongue, throat, hands, or feet. In severe cases, the throat may swell, obstructing the airway and leading to breathing difficulty. ACE inhibitors prevent the breakdown of a natural chemical in the body called bradykinin. Increased levels of bradykinin, which can cause swelling, may contribute to the development of angioedema. Blocking bradykinin receptor cells prevents bradykinin from initiating swelling and may lead to a possible decrease in angioedema symptoms. The purpose of this study is to evaluate the effectiveness of HOE-140, a bradykinin receptor blocker, at reducing symptoms in people with ACE inhibitor-associated angioedema. This study will enroll people admitted to the emergency room or hospital who have a severe case of ACE inhibitor-associated angioedema. Participants will be randomly assigned to receive an injection of either HOE-140 or placebo. Initially, participants will undergo an electrocardiogram to measure the electrical activity of the heart. Then blood pressure measurements, blood collection, a physical exam to determine the extent and duration of swelling, and photographs of the swelling will occur at 2, 4, 8, 16, and 24 hours following the start of treatment. Questionnaires will be completed by study staff and participants to assess changes in angioedema symptoms and the extent of swelling. Participants will remain in the hospital for 24 to 48 hours, depending on the severity of their symptoms. Blood will be collected at a follow-up visit that will occur 7 days after the resolution of angioedema symptoms.

Official Title
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Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial

Conditions
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ACE Inhibitor-associated Angioedema

Intervention / Treatment
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* Drug: icatibant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has ongoing angioedema while taking an ACE inhibitor. The subject is between 18 and 80 years of age. Exclusion Criteria: The subject has had angioedema while not taking an ACE inhibitor. The subject's angioedema only involves the bowel. The subject is known to be pregnant or has a positive urine pregnancy test. The subject has started on an oral contraceptive within the last 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: icatibant<br>30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization | Drug: icatibant<br>* Subcutaneous at time 0 and 6 hours<br>* Other names: HOE140;|
| Placebo Comparator: Placebo<br>Subcutaneous at time 0 and 6 hours | Other: Placebo<br>* Subcutaneous at time 0 and 6 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Resolution of Angioedema | Time interval between initiation of treatment and when there is no symptom, by visual analog scale <1 cm. Data provided are for worst symptom. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Admission to Intensive Care Unit |  | T0 to T48 hours | 
| Number of Participants With Requirement for Intubation |  | T0 to T48 hours | 
| Number of Participants Given Steroids |  | T0 to T48 hours | 
| Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers |  | T0 to T48 hours | 
| Number of Participants Given Epinephrine |  | T0 to T48 hours | 
| Systolic Blood Pressure | Average of blood pressure measurements from zero to forty-eight hours provided. | T0 to T48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACE inhibitor, Angioedema, Bradykinin, Swelling