Bradykinin Receptor Blocker in ACE Inhibitor-associated Angioedema

• ClinicalTrials.gov Identifier: NCT00517582
• Recruitment Status: Terminated
• First Posted: August 17, 2007
• Last Update Posted: December 18, 2015
• Sponsor: Vanderbilt University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Nancy J. Brown, Vanderbilt University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Angioneurotic Edema	Drug: HOE-140; Other: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study of a Bradykinin Receptor Blocker in Angiotensin Converting Enzyme Inhibitor-Associated Angioedema
• Study Start Date: September 2007
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: HOE-140; Administration of HOE-140 (icatibant) 30 mg at time 0 and at 6 hours	Drug: HOE-140; Subcutaneous at time 0 and 6 hours; Other Name: icatibant
Placebo Comparator: Placebo; Administration of placebo at time 0 and 6 hours	Other: Placebo; Subcutaneous at time 0 and 6 hours

Outcome Measures

Primary Outcome Measures :

1. Time to resolution of angioedema, as defined as the time interval between when the participant first noted the onset of symptoms and when there is no objective evidence of angioedema by physical examination [ Time Frame: Measured at follow-up visit 7 days following resolution of angioedema ]

Secondary Outcome Measures :

1. Length of hospital stay, admission to the intensive care unit, requirement for intubation, duration of intubation, use of steroids, use of histamine receptor type 1 (H1) and H2 blockers, use of epinephrine, and blood pressure levels [ Time Frame: Measured at follow-up visit 7 days following resolution of angioedema ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37205

Sponsors and Collaborators

Vanderbilt University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Nancy J. Brown, MD; Vanderbilt University Medical Center

More Information

• Responsible Party: Nancy J. Brown, Professor, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00517582
• Other Study ID Numbers: 495; R01HL079184 ( U.S. NIH Grant/Contract ); HL079184-Specific Aim 1
• First Posted: August 17, 2007
• Last Update Posted: December 18, 2015
• Last Verified: December 2015

Keywords provided by Nancy J. Brown, Vanderbilt University:

ACE Inhibitor; Angioedema; Bradykinin; Swelling

Additional relevant MeSH terms:

Angioedema; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Icatibant; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors