AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
Primary Purpose
Angioedema
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Icatibant (subcutaneous) and plazebo (intravenous)
Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
Sponsored by
About this trial
This is an interventional treatment trial for Angioedema focused on measuring ACE inhibitor induced angioedema, Bradykinin, Non-itching edema, Non-allergic angioedema, Quincke edema, Drug induced angioedema, Bradykinin B2 receptor antagonist, Icatibant, HOE 140
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 <85 years
- Patient is currently treated with an ACEI
- Patient must have acute angioedema attack caused by an ACEI
- Treatment should be administrated within 10 hrs after onset by an ACEI
- Patient with angioedema of head and /or neck (face, lips, cheeks, tongue, soft palate/uvula, pharynx and larynx)
- At least one moderate to severe severe angioedema symptom as assessed by the investigator, requiring a medical intervention
- Signed written Informed Consent Form
Exclusion Criteria:
- Diagnosis of angioedema that was not caused by ACEI: e.g. hereditary angioedema (C1-INH deficiency), allergy, anaphylaxis, insect bite, trauma, infection, abscess, tumor, post-radiation or post-operative or processes related to salivary glands and others where it is unlikely that the ACEI is causing the angioedema
- Participation in a clinical trial of another investigational medicinal product (IMP) within 30 days
- Patients with acute urticaria
- Patients with a medical history of any angioedema before taking an ACEI
- Patients with an acute rash or hives in the face or somewhere else
- Unstable angina or acute myocardial infarction
- Acute heart failure
- Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial
- Pregnancy and/or breast-feeding
- Mental condition rendering the patients, in the opinion of the investigator, unable to understand the nature, scope and possible consequences of the study;
- Unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for the follow-up visit, or unlikely to complete the study for any reason.
Sites / Locations
- Klinikum rechts der Isar Hals-Nasen-Ohrenklinik der TUM
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm Description
Outcomes
Primary Outcome Measures
Time to complete resolution of angioedema
Secondary Outcome Measures
Full Information
NCT ID
NCT01154361
First Posted
June 29, 2010
Last Updated
December 22, 2011
Sponsor
Technical University of Munich
1. Study Identification
Unique Protocol Identification Number
NCT01154361
Brief Title
AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
Official Title
A Multicenter Study, Randomized, Double-blind With 2 Groups as Prove of Concept for the Treatment of ACEI Induced Angioedema With Subcutaneous Icatibant
Study Type
Interventional
2. Study Status
Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Technical University of Munich
4. Oversight
5. Study Description
Brief Summary
This is a multicenter study recruiting patients with angioedema induced by ACEI.
Open-label treatment with subcutaneous Icatibant compared to a historic group of 47 patients with ACE inhibitor induced angioedema which the investigators have been previously treated in the investigators centers with current "standard" therapy (250 mg methylprednisolon and 2 mg clemastine).
In cases with fast progression of edema after application the study-drug, a second application with icatibant could be necessary. Rescue medication and intervention.
Detailed Description
Sudden occurrence of subcutaneous or submucosal non-itchy swelling, so-called angioedema, is a well known side effect of angiotensin-converting enzyme inhibitors (ACEi), which may become life-threatening if the upper airway is involved. To be note, ACEi induced angioedema were always located in the head and neck region.
The pathophysiology of ACE inhibitor (ACEi) induced angioedema most likely resembles that of hereditary angioedema (HAE), i.e. it is mainly mediated by bradykinin induced activation of vascular bradykinin B2 receptors (BKR-2). In contrast to an increased bradykinin generation in HAE, treatment with ACEi decreases the bradykinin degradation in plasma and increases the biological activity of bradykinin.
The current pharmacotherapy of ACEi induced angioedema is not satisfactory. Antihistamines and corticosteroids may be effective in the treatment of urticaria with cutaneous edema and itchy, but are theoretically ineffective and hence superfluous in bradykinin induced angioedema. However, glucocorticoids still belong to the standard treatment of angioedema.
We hypothesized that the BKR-2 antagonist icatibant might be an effective therapy for ACEi-induced angioedema.
Patients with ACEi induced angioedema, located in the upper aero-digestive tract will be randomized and treated either with icatibant and plazebo or cortisone with clemastin and plazebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angioedema
Keywords
ACE inhibitor induced angioedema, Bradykinin, Non-itching edema, Non-allergic angioedema, Quincke edema, Drug induced angioedema, Bradykinin B2 receptor antagonist, Icatibant, HOE 140
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Title
Arm B
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Icatibant (subcutaneous) and plazebo (intravenous)
Intervention Type
Drug
Intervention Name(s)
Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
Primary Outcome Measure Information:
Title
Time to complete resolution of angioedema
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >= 18 <85 years
Patient is currently treated with an ACEI
Patient must have acute angioedema attack caused by an ACEI
Treatment should be administrated within 10 hrs after onset by an ACEI
Patient with angioedema of head and /or neck (face, lips, cheeks, tongue, soft palate/uvula, pharynx and larynx)
At least one moderate to severe severe angioedema symptom as assessed by the investigator, requiring a medical intervention
Signed written Informed Consent Form
Exclusion Criteria:
Diagnosis of angioedema that was not caused by ACEI: e.g. hereditary angioedema (C1-INH deficiency), allergy, anaphylaxis, insect bite, trauma, infection, abscess, tumor, post-radiation or post-operative or processes related to salivary glands and others where it is unlikely that the ACEI is causing the angioedema
Participation in a clinical trial of another investigational medicinal product (IMP) within 30 days
Patients with acute urticaria
Patients with a medical history of any angioedema before taking an ACEI
Patients with an acute rash or hives in the face or somewhere else
Unstable angina or acute myocardial infarction
Acute heart failure
Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial
Pregnancy and/or breast-feeding
Mental condition rendering the patients, in the opinion of the investigator, unable to understand the nature, scope and possible consequences of the study;
Unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for the follow-up visit, or unlikely to complete the study for any reason.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Murat Bas, Dr.
Organizational Affiliation
Klinikum rechts der Isar, Hals-Nasen-Ohrenklinik, Ismaninger Str. 22 81675 München
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum rechts der Isar Hals-Nasen-Ohrenklinik der TUM
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81675
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
25629740
Citation
Bas M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. doi: 10.1056/NEJMoa1312524.
Results Reference
derived
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AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
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