Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement

NCT00448864 | Terminated Phase 2 Results DMC

• 2 other identifiers: 1501-001DX-88/16
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 15

Brief Summary

The primary objective of this study was to assess the efficacy and safety of 2 dose levels of ecallantide versus placebo in reducing blood loss following cardiopulmonary bypass (CPB), as measured by chest tube drainage during the first 12 hours postoperatively or until the chest tube was removed, whichever came first, in patients undergoing primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement. The secondary objective was to compare the efficacy of all ecallantide-treated participants (pooled high and low-doses) to placebo and to compare the high-dose to the low-dose ecallantide group. Other secondary objectives were to evaluate pharmacokinetics and antibody formation.

Conditions

Blood Loss, Surgical

Outcome Measures

Primary Outcomes (1)

• Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively

  Mean volume of chest tube drainage during the first 12 hours postoperatively or until chest tube removal, whichever occurred first, is presented for each treatment group.

  Up to 12 hours post admission to intensive care unit (ICU)

Secondary Outcomes (3)

• Cumulative Chest Tube Drainage at 24 Hours Postoperatively

  Up to 24 hours post admission to ICU

• Number of Participants With Treatment-emergent Adverse Events

  up to 28 days post admission to ICU

• Pharmacokinetics: Area Under the Concentration Time Curve

  1, 2, 4, and 8 hours after end of study drug infusion

Study Arms (3)

Ecallantide - Low Dose Regimen

EXPERIMENTAL

Participants received a maximum of 15 milligrams (mg) ecallantide in stages. Intravenous (IV) infusion of 0.6 milligrams per milliliter (mg/mL) ecallantide was administered at 2.92 milliliters per minute (mL/min) for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of cardiopulmonary bypass (CPB), whichever came first. At the termination of the initial infusion, a second infusion of 0.4 mg/mL ecallantide was started at 38 milliliters per hour (mL/hr) for 4 hours.

Drug: Ecallantide

Ecallantide - High Dose Regimen

EXPERIMENTAL

Participants received a maximum of 91 mg ecallantide in stages. IV infusion of 0.6 mg/mL ecallantide was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, an infusion of normal saline was started at 38 milliliters per hour (mL/hr) for 4 hours.

Drug: Ecallantide

Placebo

PLACEBO COMPARATOR

Participants received placebo in stages. IV infusion placebo was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, a second infusion of placebo was started at 38 mL/hr for 4 hours.

Drug: Placebo

Interventions

Ecallantide DRUG

Also known as: DX-88

Ecallantide - High Dose Regimen; Ecallantide - Low Dose Regimen

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥18 to ≤85 years of age
• Elective primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement requiring CPB and full sternotomy
• No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone, E-aminocaproic acid (EACA), tranexamic acid, or aprotinin during or postoperatively
• Female participants must be non-lactating and not pregnant
• If of childbearing potential, female participants must agree to use adequate contraception for 1 month after receiving study drug

You may not qualify if:

• Concomitant surgery including but not limited to atrial septal defect repair, multiple valve replacement, carotid endarterectomy, and combined CABG and valve procedure
• Planned hypothermic CPB using temperatures less than 28 degrees Celsius
• Weight \<55 kilograms (kg)
• Major end organ dysfunction, defined as:
• Cardiac:
• Left ventricular ejection fraction (LVEF) \< 30% by left ventriculography, echocardiogram, or catheterization (within 90 days prior to screening)
• Use of positive IV inotropic agents within 12 hours prior to surgery
• Preoperative use of intra-aortic balloon pump (IABP), left ventricular assist device (LVAD), or extracorporeal membrane oxygenation (ECMO)
• Renal: Serum creatinine \> 1.5 milligrams per deciliter (mg/dL)
• Hepatic: Aspartate aminotransferase (AST) or alanine transferase (ALT) \> 2.5 x upper limit normal
• Hematologic:
• Preoperative hematocrit (Hct) \< 30%
• Platelet count \< 100,000/mm\^3
• Planned transfusion during surgical procedure
• History or family history of bleeding or clotting disorder (for example, von Willebrand's Disease, idiopathic thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), hematologic malignancy)

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (15)

St. Vincent's Hospital

Birmingham, Alabama, 35205, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Caritas St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Gaston Memorial Hospital

Gastonia, North Carolina, 28054, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Heart Institute

Houston, Texas, 77225, United States

Location

MeSH Terms

Conditions

Blood Loss, Surgical

Interventions

ecallantide

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: Cubist Pharmaceuticals

(781) 860-8660

Study Officials

• Andrew L Sternlicht, MD

  Dyax Corp.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2007
• First Posted: March 19, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: August 1, 2008
• Last Updated: June 25, 2019
• Results First Posted: July 8, 2015

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

US (15)