ACE: Evaluation of Ecallantide for the Acute Treatment of Angiotensin Converting Enzyme Inhibitor Induced Angioedema

Sponsor

Bernstein, Jonathan A., M.D. (Other)

Overall Status

Unknown status

CT.gov ID

NCT01036659

Collaborator

Dyax Corp. (Industry)

Enrollment

Locations

Arms

Duration (Months)

16.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will conduct a double-blind, randomized controlled trial comparing the safety and effectiveness of ecallantide to conventional therapy. A rescue cross-over design will be used such that patients failing to improve on standard therapy will additionally be treated with ecallantide. Therefore, a historical control cohort will be enrolled for analysis of secondary endpoints. In addition, since some patients treated with conventional therapy may improve rapidly and therefore not be eligible for inclusion in the study, the investigators will enroll these patients as an observational arm to enable the conduct of sensitivity analysis.

Condition or Disease	Intervention/Treatment	Phase
Angioedema	Drug: ecallantide - Kallikrein inhibitor that blocks the production of bradykinin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Evaluation of Ecallantide for Acute Treatment of Angiotensin Converting Enzyme Inhibitor Induced Angioedema

Study Start Date :

May 1, 2010

Anticipated Primary Completion Date :

Jun 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ecallantide in conjunction with Conventional Therapy	Drug: ecallantide - Kallikrein inhibitor that blocks the production of bradykinin subcutaneous dose of 30mg of ecallantide or placebo (three 10 mg SC injections at three different sites ((arms, legs, abdomen). Injections are not to be administered at the attack location.
Placebo Comparator: Conventional therapy and placebo	Drug: ecallantide - Kallikrein inhibitor that blocks the production of bradykinin subcutaneous dose of 30mg of ecallantide or placebo (three 10 mg SC injections at three different sites ((arms, legs, abdomen). Injections are not to be administered at the attack location.
No Intervention: Historical Evaluation

Arm

Intervention/Treatment

Active Comparator: Ecallantide in conjunction with Conventional Therapy

Drug: ecallantide - Kallikrein inhibitor that blocks the production of bradykinin

subcutaneous dose of 30mg of ecallantide or placebo (three 10 mg SC injections at three different sites ((arms, legs, abdomen). Injections are not to be administered at the attack location.

Placebo Comparator: Conventional therapy and placebo

Drug: ecallantide - Kallikrein inhibitor that blocks the production of bradykinin

subcutaneous dose of 30mg of ecallantide or placebo (three 10 mg SC injections at three different sites ((arms, legs, abdomen). Injections are not to be administered at the attack location.

No Intervention: Historical Evaluation

Outcome Measures

Primary Outcome Measures

Objective criteria that allow for discharge directly from the ED at or before 4 hours:(stable vital signs, no evidence of stridor, dysphagia or drooling, edema has regressed to or did not progress beyond Class I. [18 months]

Secondary Outcome Measures

Time to meet objective discharge criteria, Physician assessment of angioedema improvement measured using the Symptom Complex Response Assessment at 2 hours post-treatment and 4 hours post-treatment. [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Males and females of any race or ethnicity 18 or older. The locations of the study will permit all racial and ethnic distribution in the study
Must currently be on an ACE inhibitor
Presenting with ACE induced angioedema within 12 hours after onset. This is to be documented in the source document and CRF
All females of childbearing age must have a negative pregnancy test prior to administration of the study drug.

Exclusion Criteria:

Participation in another investigational study within 30 days prior to enrollment
Patients who improve on conventional (standard of care) therapy
Patients previously treated with ecallantide
Hypersensitivity to ecallantide
Pregnancy or breast feeding
Other definable causes of angioedema (i.e., hereditary or acquired angioedema)
Patients receiving C-1 inhibitor as prophylaxis
Treatment requiring tranexamic acid, and epsilon-aminocaproic acid
Receiving fresh frozen plasma within 3 days prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Jewish Hospital	Cincinnati	Ohio	United States	45201
2	Univeristy Hospital	Cincinnati	Ohio	United States	45219
3	UC Physicians, Dpt of Internal Medicine, Division of Immunology	Cincinnati	Ohio	United States	45267

Sponsors and Collaborators

Bernstein, Jonathan A., M.D.
Dyax Corp.

Investigators

Principal Investigator: Jonathan A. Bernstein, M.D., UC Physicians, Division of Immunology
Principal Investigator: Joseph Moellman, MD, UC Physicians, Department of Emergency Medicine