Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema

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

A double-blind, randomized, controlled trial comparing the safety and effectiveness of conventional therapy with ecallantide to conventional therapy with placebo.

Study Overview

• Status: Terminated
• Conditions: ACE Inhibitor Induced Angioedema
• Intervention / Treatment: Drug: ecallantide 10 mg; Drug: placebo match for 10 mg ecallantide arm; Drug: placebo; Drug: ecallantide 60 mg; Drug: ecallantide 30 mg; Drug: placebo match for 30 mg ecallantide arm

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Er Med, Llc
  • California
    • Colton, California, United States, 92324
      • Arrowhead Regional Medical Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles School of Medicine
    • San Diego, California, United States, 92103
      • University of California San Diego Mecial Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Hospital, Department of Emergency Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy and Immunology
    • Chicago, Illinois, United States, 60616
      • Mercy Hospital and Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital, Royal Oak
    • Troy, Michigan, United States, 48085
      • Beaumont Hospital, Troy
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Acess to Research and Education Study
  • New York
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital Center
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • The MetroHealth System
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
    • Columbus, Ohio, United States, 43205
      • University Hospital East
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78701
      • University Medical Center Brackenridge
    • Bryan, Texas, United States, 77802
      • St Joseph Regional Health Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center at Dallas
    • Fort Worth, Texas, United States, 76104
      • Emergency Medicine Residency Program
    • Galveston, Texas, United States, 77555
      • 301 University Blvd.
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18 years of age or older
• Must currently be on ACE inhibitor therapy and have received a dose within 36 hours
• Presenting with ACEIA of the head/neck region within 12 hours after onset
• All females must have a negative urine pregnancy test prior to administration of the study drug. Those who have had a total hysterectomy, bilateral oophorectomy or are two years post-menopausal do not require a pregnancy test.

Exclusion Criteria:

• Hypersensitivity to ecallantide
• Pregnancy or breast feeding
• Patients who have had angioedema and were not concurrently on an ACE inhibitor
• Patients exhibiting urticaria
• Patients who are intubated or who have a tracheostomy related to the current episode of angioedema
• Opinion of the investigator that the patient would not be a good candidate
• Participation in another investigational study within 30 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ecallantide 10mg; Administered as one 3 mL SC injection containing 10 mg ecallantide and one 3 mL SC injection of matching placebo.	Drug: ecallantide 10 mg; Administered as one 3 mL SC injection containing 10 mg ecallantide.; Drug: placebo match for 10 mg ecallantide arm; One 3 mL SC injection of matching placebo given to subjects randomized to the 10 mg ecallantide arm.
PLACEBO_COMPARATOR: placebo; Administered as two SC 3 mL injections	Drug: placebo; Administered as two SC 3 mL injections
ACTIVE_COMPARATOR: ecallantide 60mg; Administered as two 3 mL SC injections, each containing 30 mg ecallantide	Drug: ecallantide 60 mg; Administered as two 3 mL SC injections, each containing 30 mg ecallantide
ACTIVE_COMPARATOR: ecallantide 30mg; Administered as one 3 mL SC injection containing 30 mg ecallantide and one 3 mL SC injection of matching placebo.	Drug: ecallantide 30 mg; Administered as one 3 mL SC injection containing 30 mg ecallantide; Drug: placebo match for 30 mg ecallantide arm; One 3 mL SC injection of matching placebo given to subjects randomized to the 30 mg ecallantide arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Efficacy of Ecallantide	Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to "a little better" or "a lot better" as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Symptom Resolution Based on the Visual Analog Scale (VAS)	Compare the time to onset of symptom resolution between the ecallantide-treated and placebo-treated groups. The patient assessed severity of the angioedema attack using a VAS at baseline and following study drug administration every 15 minutes for the first 2 hours and then every 30 minutes through 6 hours post dosing or until the time of discharge from the ER (whichever occurred first). The scale ranged from "totally resolved" to "very severe".	6 hours

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, Miner J, Iarrobino R, Chyung Y. Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med. 2015 Feb;65(2):204-13. doi: 10.1016/j.annemergmed.2014.07.014. Epub 2014 Aug 30.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2011
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: April 27, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (ESTIMATE): April 28, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Angioedema; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Ecallantide
• Other Study ID Numbers: DX-88/27