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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)

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

18 Years - 84 Years (Adult, Older Adult)All SexesDoes not accept 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.

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

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Primary Completion Date

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Study Completion Date

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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

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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