AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study - Full Text View

Purpose

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	Intervention	Phase
Angioedema	Drug: Icatibant (subcutaneous) and plazebo (intravenous) Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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 NLM:

Drug Information available for: Icatibant acetate

U.S. FDA Resources

Further study details as provided by Technische Universität München:

Primary Outcome Measures:

Time to complete resolution of angioedema

Arms	Assigned Interventions
Experimental: Arm A	Drug: Icatibant (subcutaneous) and plazebo (intravenous)
Active Comparator: Arm B	Drug: Cortisone + Clemastin (intravenous) and plazebo (subcutaneous)

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.

Eligibility


Ages Eligible for Study:	18 Years to 84 Years
Genders Eligible for Study:	Both
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

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154361

Locations


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

Sponsors and Collaborators

Technische Universität München

Investigators


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

More Information

No publications provided by Technische Universität München

Additional 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.


ClinicalTrials.gov Identifier:	NCT01154361 History of Changes
Other Study ID Numbers:	AMACE
Study First Received:	June 29, 2010
Last Updated:	December 22, 2011
Health Authority:	Germany: Regierung von Oberbayern

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:


Angioedema Cardiovascular Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Skin Diseases Skin Diseases, Vascular Urticaria Vascular Diseases Angiotensin-Converting Enzyme Inhibitors Icatibant Adrenergic Agents Adrenergic Antagonists Adrenergic beta-Antagonists Analgesics	Analgesics, Non-Narcotic Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal Antirheumatic Agents Central Nervous System Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Protease Inhibitors Sensory System Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015