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Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01574248
Recruitment Status : Terminated (DSMC recommended discontinuation for futility and feasibility)
First Posted : April 10, 2012
Results First Posted : February 17, 2017
Last Update Posted : February 17, 2017
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University Medical Center

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
ACE Inhibitor-associated Angioedema Drug: icatibant Other: Placebo Phase 4

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 : 33 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial
Study Start Date : August 2011
Actual Primary Completion Date : September 2015
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: icatibant
30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization
Drug: icatibant
Subcutaneous at time 0 and 6 hours
Other Names:
  • Firazyr
  • HOE140

Placebo Comparator: Placebo
Subcutaneous at time 0 and 6 hours
Other: Placebo
Subcutaneous at time 0 and 6 hours

Primary Outcome Measures :
  1. Time to Resolution of Angioedema [ Time Frame: 48 hours ]
    Time interval between initiation of treatment and when there is no symptom, by visual analog scale <1 cm. Data provided are for worst symptom.

Secondary Outcome Measures :
  1. Number of Participants With Admission to Intensive Care Unit [ Time Frame: T0 to T48 hours ]
  2. Number of Participants With Requirement for Intubation [ Time Frame: T0 to T48 hours ]
  3. Number of Participants Given Steroids [ Time Frame: T0 to T48 hours ]
  4. Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers [ Time Frame: T0 to T48 hours ]
  5. Number of Participants Given Epinephrine [ Time Frame: T0 to T48 hours ]
  6. Systolic Blood Pressure [ Time Frame: T0 to T48 hours ]
    Average of blood pressure measurements from zero to forty-eight hours provided.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

  • 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.

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 identifier (NCT number): NCT01574248

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United States, California
University of California, San Diego
San Diego, California, United States, 92093
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37235
Sponsors and Collaborators
Vanderbilt University Medical Center
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Principal Investigator: Nancy J. Brown, MD Vanderbilt University

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Responsible Party: Nancy J. Brown, Chair Department of Medicine, Vanderbilt University Medical Center Identifier: NCT01574248    
Other Study ID Numbers: 000626
First Posted: April 10, 2012    Key Record Dates
Results First Posted: February 17, 2017
Last Update Posted: February 17, 2017
Last Verified: December 2016
Keywords provided by Nancy J. Brown, Vanderbilt University Medical Center:
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