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.

ClinicalTrials.gov Identifier: NCT01154361

Recruitment Status : Completed

First Posted : June 30, 2010

Last Update Posted : December 23, 2011

Sponsor:

Information provided by:

Technische Universität München

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.

Condition or disease	Intervention/treatment	Phase
Angioedema	Drug: Icatibant (subcutaneous) and plazebo (intravenous) Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)	Phase 2

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Cortisone Icatibant Icatibant acetate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A	Drug: Icatibant (subcutaneous) and plazebo (intravenous)
Active Comparator: Arm B	Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)

Outcome Measures

Primary Outcome Measures :

Time to complete resolution of angioedema

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 84 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01154361

Locations

Layout table for location information

Germany
Klinikum rechts der Isar Hals-Nasen-Ohrenklinik der TUM
Munich, Bavaria, Germany, 81675

Sponsors and Collaborators

Technische Universität München

Investigators

Layout table for investigator information

Principal Investigator:	Murat Bas, Dr.	Klinikum rechts der Isar, Hals-Nasen-Ohrenklinik, Ismaninger Str. 22 81675 München

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

ClinicalTrials.gov Identifier:	NCT01154361
Other Study ID Numbers:	AMACE
First Posted:	June 30, 2010 Key Record Dates
Last Update Posted:	December 23, 2011
Last Verified:	December 2011

Keywords provided by Technische Universität München:


ACE inhibitor induced angioedema Bradykinin Non-itching edema Non-allergic angioedema Quincke edema	Drug induced angioedema Bradykinin B2 receptor antagonist Icatibant HOE 140

Additional relevant MeSH terms:

Layout table for MeSH terms

Angioedema Vascular Diseases Cardiovascular Diseases Urticaria Skin Diseases, Vascular Skin Diseases Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Cortisone Icatibant Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal	Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Antirheumatic Agents Bradykinin B2 Receptor Antagonists Bradykinin Receptor Antagonists Molecular Mechanisms of Pharmacological Action Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors

To Top