Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema

December 22, 2016 updated by: Nancy J. Brown, Vanderbilt University Medical Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92093
        • University of California, San Diego
    • Tennessee
      • Nashville, Tennessee, United States, 37235
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Admission to Intensive Care Unit
Time Frame: T0 to T48 hours
T0 to T48 hours
Number of Participants With Requirement for Intubation
Time Frame: T0 to T48 hours
T0 to T48 hours
Number of Participants Given Steroids
Time Frame: T0 to T48 hours
T0 to T48 hours
Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers
Time Frame: T0 to T48 hours
T0 to T48 hours
Number of Participants Given Epinephrine
Time Frame: T0 to T48 hours
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.
T0 to T48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

Shire

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (ACTUAL)

September 1, 2015

Study Completion (ACTUAL)

February 1, 2016

Study Registration Dates

First Submitted

December 14, 2011

First Submitted That Met QC Criteria

April 5, 2012

First Posted (ESTIMATE)

April 10, 2012

Study Record Updates

Last Update Posted (ACTUAL)

February 17, 2017

Last Update Submitted That Met QC Criteria

December 22, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000626

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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