AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study

Sponsor

Technische Universität München (Other)

Overall Status

Completed

CT.gov ID

NCT01154361

Collaborator

(none)

Location

Arms

Study Details

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

Study Type:

Interventional

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

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)

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

Criteria

Ages Eligible for Study:

18 Years to 84 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.