Clinical Trial: Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial

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 Summary:

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.


Sponsor: Vanderbilt University Medical Center

Current Primary Outcome: 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.


Original Primary Outcome: Time to Resolution of Angioedema [ Time Frame: 48 hours ]

Time interval between when participant first noted the onset of symptom and when there is no symptom, by visual analog scale. Will also measure AUC for VAS versus time for each symptom


Current Secondary Outcome:

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


Original Secondary Outcome:

  • Length of hospital stay [ Time Frame: T0 to T48 hours ]
  • Admission to intensive care unit [ Time Frame: T0 to T48 hours ]
  • Requirement for intubation [ Time Frame: T0 to T48 hours ]
  • Duration of intubation [ Time Frame: T0 to T48 hours ]
  • Use of steroids [ Time Frame: T0 to T48 hours ]
  • Use of histamine receptor type 1 (H1) and type 2 (H2) blockers [ Time Frame: T0 to T48 hours ]
  • Use of epinephrine [ Time Frame: T0 to T48 hours ]
  • Blood pressure levels [ Time Frame: T0 to T48 hours ]


Information By: Vanderbilt University Medical Center

Dates:
Date Received: December 14, 2011
Date Started: August 2011
Date Completion:
Last Updated: December 22, 2016
Last Verified: December 2016