- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01574248
Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema
Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial
Study Overview
Status
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92093
- University of California, San Diego
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Tennessee
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Nashville, Tennessee, United States, 37235
- Vanderbilt University Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
|
Subcutaneous at time 0 and 6 hours
Other Names:
|
PLACEBO_COMPARATOR: Placebo
Subcutaneous at time 0 and 6 hours
|
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
Collaborators
Investigators
- Principal Investigator: Nancy J. Brown, MD, Vanderbilt University
Publications and helpful links
General Publications
- Byrd JB, Adam A, Brown NJ. Angiotensin-converting enzyme inhibitor-associated angioedema. Immunol Allergy Clin North Am. 2006 Nov;26(4):725-37. doi: 10.1016/j.iac.2006.08.001.
- Brown NJ, Ray WA, Snowden M, Griffin MR. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996 Jul;60(1):8-13. doi: 10.1016/S0009-9236(96)90161-7.
- Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension. 2009 Sep;54(3):516-23. doi: 10.1161/HYPERTENSIONAHA.109.134197. Epub 2009 Jul 6.
- Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med. 1998 Oct 29;339(18):1285-92. doi: 10.1056/NEJM199810293391804.
- Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. No abstract available.
- Verresen L, Fink E, Lemke HD, Vanrenterghem Y. Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes. Kidney Int. 1994 May;45(5):1497-503. doi: 10.1038/ki.1994.195.
- Krieter DH, Grude M, Lemke HD, Fink E, Bonner G, Scholkens BA, Schulz E, Muller GA. Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin. Kidney Int. 1998 Apr;53(4):1026-35. doi: 10.1111/j.1523-1755.1998.00837.x.
- Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W. Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol. 2007 Jun;119(6):1497-503. doi: 10.1016/j.jaci.2007.02.012. Epub 2007 Apr 5.
- Brown NJ, Snowden M, Griffin MR. Recurrent angiotensin-converting enzyme inhibitor--associated angioedema. JAMA. 1997 Jul 16;278(3):232-3. doi: 10.1001/jama.278.3.232.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Immune System Diseases
- Hypersensitivity, Immediate
- Skin Diseases, Vascular
- Hypersensitivity
- Urticaria
- Angioedema
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Complement Inactivating Agents
- Bradykinin B2 Receptor Antagonists
- Bradykinin Receptor Antagonists
- Icatibant
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.
Clinical Trials on ACE Inhibitor-associated Angioedema
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ShireTerminatedACE Inhibitor Induced AngioedemaUnited States
-
Pharvaris Netherlands B.V.RecruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States
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Pharvaris Netherlands B.V.RecruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Bulgaria, Czechia, Hungary, Spain, France, Germany, Poland, Canada, Israel
-
Pharvaris Netherlands B.V.Active, not recruitingHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsUnited States, Poland, Germany, Austria, Bulgaria, Canada, Ireland, Italy, United Kingdom
-
Pharvaris Netherlands B.V.CompletedHereditary Angioedema | Hereditary Angioedema Type I | Hereditary Angioedema Type II | Hereditary Angioedema Types I and II | Hereditary Angioedema Attack | Hereditary Angioedema With C1 Esterase Inhibitor Deficiency | Hereditary Angioedema - Type 1 | Hereditary Angioedema - Type 2 | C1 Esterase Inhibitor... and other conditionsBulgaria, United States, Spain, Israel, Germany, Canada, Czechia, France, Hungary, Italy, Netherlands, Poland, United Kingdom
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