Clinical trial NCT01574248: Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema
Official title: Effect of Bradykinin Receptor Antagonism on ACE Inhibitor-associated Angioedema - a Mulitcenter Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: ACE Inhibitor-associated Angioedema
Keywords: ACE inhibitor
Angioedema
Bradykinin
Swelling
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2012-04-10
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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 criteria: 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.

Primary outcomes:
measure: Time to Resolution of Angioedema
timeFrame: 48 hours
Secondary outcomes:
measure: Number of Participants With Admission to Intensive Care Unit
timeFrame: T0 to T48 hours
measure: Number of Participants With Requirement for Intubation
timeFrame: T0 to T48 hours
measure: Number of Participants Given Steroids
timeFrame: T0 to T48 hours
measure: Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers
timeFrame: T0 to T48 hours
measure: Number of Participants Given Epinephrine
timeFrame: T0 to T48 hours
measure: Systolic Blood Pressure
timeFrame: T0 to T48 hours
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Nancy J. Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.