Effectiveness of Bradykinin Receptor Blocker at Reducing Swelling Associated With Angiotensin Converting Enzyme (ACE) Inhibitor-Associated Angioedema

This study has been terminated.
(This study was stopped to allow initiation of a mult-center study)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00517582
First received: August 15, 2007
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Angioneurotic Edema
Drug: HOE-140
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of a Bradykinin Receptor Blocker in Angiotensin Converting Enzyme Inhibitor-Associated Angioedema

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: September 2007
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HOE-140 Drug: HOE-140
Subcutaneous at time 0 and 6 hours
Placebo Comparator: Placebo Other: Placebo
Subcutaneous at time 0 and 6 hours

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517582

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37205
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Nancy J. Brown, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Nancy J. Brown, Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00517582     History of Changes
Other Study ID Numbers: 495, R01HL079184, HL079184-Specific Aim 1
Study First Received: August 15, 2007
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
ACE Inhibitor
Angioedema
Bradykinin
Swelling

Additional relevant MeSH terms:
Angioedema
Edema
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Signs and Symptoms
Angiotensin-Converting Enzyme Inhibitors
Bradykinin
Kininogens
Enzyme Inhibitors
Icatibant
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Cysteine Proteinase Inhibitors
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on August 01, 2014