Bradykinin Receptor Blocker in ACE Inhibitor-associated Angioedema

NCT ID: NCT00517582

Last Updated: 2015-12-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2015-12-31

Brief Summary

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

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.

Conditions

Angioneurotic Edema

Keywords

ACE Inhibitor; Angioedema; Bradykinin; Swelling

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

HOE-140

Administration of HOE-140 (icatibant) 30 mg at time 0 and at 6 hours

Group Type: EXPERIMENTAL

HOE-140

Intervention Type: DRUG

Subcutaneous at time 0 and 6 hours

Placebo

Administration of placebo at time 0 and 6 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subcutaneous at time 0 and 6 hours

Interventions

HOE-140

Subcutaneous at time 0 and 6 hours

Intervention Type: DRUG

Placebo

Subcutaneous at time 0 and 6 hours

Intervention Type: OTHER

Other Intervention Names

icatibant

Eligibility Criteria

Inclusion Criteria

• Ambulatory
• ACE inhibitor-associated angioedema, as defined as swelling of the lips, pharynx, or face while taking an ACE inhibitor, no history of angioedema while not taking an ACE inhibitor, and no evidence of abnormal C1 inhibitor concentration or abnormal complement levels. People with possible cases of ACE inhibitor-associated bowel edema will not be enrolled.
• If female, must be postmenopausal for at least 1 year prior to study entry, undergone surgical sterilization, or willing to use an effective form of birth control and take a pregnancy test daily for the duration of the study

Exclusion Criteria

• Pregnant or breastfeeding
• Started taking birth control pills in the 6 months prior to study entry

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Nancy J. Brown

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy J. Brown, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

R01HL079184

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HL079184-Specific Aim 1

Identifier Type: -

Identifier Source: secondary_id

495

Identifier Type: -

Identifier Source: org_study_id