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Bradykinin Receptor Blocker in ACE Inhibitor-associated Angioedema

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ClinicalTrials.gov Identifier: NCT00517582
Recruitment Status : Terminated (This study was stopped to allow initiation of a mult-center study)
First Posted : August 17, 2007
Last Update Posted : December 18, 2015
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University

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.

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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

Resource links provided by the National Library of Medicine

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

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 ]

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00517582

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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37205
Sponsors and Collaborators
Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Nancy J. Brown, MD Vanderbilt University Medical Center
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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    Key Record Dates
Last Update Posted: December 18, 2015
Last Verified: December 2015
Keywords provided by Nancy J. Brown, Vanderbilt University:
ACE Inhibitor
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
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