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DSMC recommended discontinuation for futility and feasibility
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| Name | Class |
|---|---|
| Shire | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| icatibant | Experimental | 30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization |
|
| Placebo | Placebo Comparator | Subcutaneous at time 0 and 6 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| icatibant | Drug | Subcutaneous at time 0 and 6 hours |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Resolution of Angioedema | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Admission to Intensive Care Unit | T0 to T48 hours | |
| Number of Participants With Requirement for Intubation | T0 to T48 hours | |
| Number of Participants Given Steroids |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nancy J. Brown, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego | San Diego | California | 92093 | United States | ||
| Vanderbilt University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17085287 | Background | 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. | |
| 8689816 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Icatibant | 30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization icatibant: Subcutaneous at time 0 and 6 hours |
| FG001 | Placebo | Subcutaneous at time 0 and 6 hours Placebo: Subcutaneous at time 0 and 6 hours |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Icatibant | 30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization icatibant: Subcutaneous at time 0 and 6 hours |
| BG001 | Placebo | Subcutaneous at time 0 and 6 hours Placebo: Subcutaneous at time 0 and 6 hours |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Resolution of Angioedema | Time interval between initiation of treatment and when there is no symptom, by visual analog scale <1 cm. Data provided are for worst symptom. | Posted | Median | 95% Confidence Interval | hours | 48 hours |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Icatibant | 30 mg icatibant will be administered subcutaneously 0 and 6 hours after randomization icatibant: Subcutaneous at time 0 and 6 hours |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| low sperm count | Reproductive system and breast disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nancy J. Brown, M.D. | Vanderbilt University Medical Center | 6153438701 | nancy.j.brown@vanderbilt.edu |
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| ID | Term |
|---|---|
| D000799 | Angioedema |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
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| ID | Term |
|---|---|
| C065679 | icatibant |
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| Placebo | Other | Subcutaneous at time 0 and 6 hours |
|
| T0 to T48 hours |
| Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers | T0 to T48 hours |
| Number of Participants Given Epinephrine | T0 to T48 hours |
| Systolic Blood Pressure | Average of blood pressure measurements from zero to forty-eight hours provided. | T0 to T48 hours |
| Nashville |
| Tennessee |
| 37235 |
| United States |
| 19581505 | Background | 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. |
| 9791144 | Background | 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. |
| 18768946 | Background | Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. No abstract available. |
| 8072263 | Background | 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. |
| 9551414 | Background | 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. |
| 17418383 | Background | 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. |
| 9218671 | Background | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | Number of Participants With Admission to Intensive Care Unit | Posted | Count of Participants | Participants | T0 to T48 hours |
|
|
|
| Secondary | Number of Participants With Requirement for Intubation | Posted | Count of Participants | Participants | T0 to T48 hours |
|
|
|
| Secondary | Number of Participants Given Steroids | Posted | Count of Participants | Participants | T0 to T48 hours |
|
|
|
| Secondary | Number of Participants Given Histamine Receptor Type 1 (H1) and Type 2 (H2) Blockers | Posted | Count of Participants | Participants | T0 to T48 hours |
|
|
|
| Secondary | Number of Participants Given Epinephrine | Posted | Count of Participants | Participants | T0 to T48 hours |
|
|
|
| Secondary | Systolic Blood Pressure | Average of blood pressure measurements from zero to forty-eight hours provided. | Posted | Mean | Standard Deviation | mmHg | T0 to T48 hours |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| EG001 | Placebo | Subcutaneous at time 0 and 6 hours Placebo: Subcutaneous at time 0 and 6 hours | 0 | 18 | 2 | 18 |
| elevated troponin | Cardiac disorders | Non-systematic Assessment |
|
| leukocytosis | Immune system disorders | Systematic Assessment |
|
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| D012871 |
| Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |