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AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01154361
Recruitment Status : Completed
First Posted : June 30, 2010
Last Update Posted : December 23, 2011
Information provided by:
Technische Universität München

Tracking Information
First Submitted Date  ICMJE June 29, 2010
First Posted Date  ICMJE June 30, 2010
Last Update Posted Date December 23, 2011
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: June¬†29,¬†2010)
Time to complete resolution of angioedema
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
Official Title  ICMJE A Multicenter Study, Randomized, Double-blind With 2 Groups as Prove of Concept for the Treatment of ACEI Induced Angioedema With Subcutaneous Icatibant
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Angioedema
Intervention  ICMJE
  • Drug: Icatibant (subcutaneous) and plazebo (intravenous)
  • Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
Study Arms  ICMJE
  • Experimental: Arm A
    Intervention: Drug: Icatibant (subcutaneous) and plazebo (intravenous)
  • Active Comparator: Arm B
    Intervention: Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)
Publications * Baş 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 84 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01154361
Other Study ID Numbers  ICMJE AMACE
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Technische Universität München
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Murat Bas, Dr. Klinikum rechts der Isar, Hals-Nasen-Ohrenklinik, Ismaninger Str. 22 81675 München
PRS Account Technische Universität München
Verification Date December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP