Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement
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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||KALAHARI-1: Kallikrein Antagonist (DX-88 [Ecallantide]) Effect on Blood Loss Associated With Heart Surgery Requiring Institution of Bypass|
- Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively [ Time Frame: Up to 12 hours post admission to intensive care unit (ICU) ]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.
- Cumulative Chest Tube Drainage at 24 Hours Postoperatively [ Time Frame: Up to 24 hours post admission to ICU ]Mean volume of chest tube drainage during the first 24 hours postoperatively or until chest tube removal, whichever occurred first, is presented for each treatment group.
- Number of Participants With Treatment-emergent Adverse Events [ Time Frame: up to 28 days post admission to ICU ]A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
- Pharmacokinetics: Area Under the Concentration Time Curve [ Time Frame: 1, 2, 4, and 8 hours after end of study drug infusion ]Results are reported in terms of the Area Under Plasma Concentration Time Curve (AUC), measured as milligram hour per liter (mg*h/L)
|Study Start Date:||May 2007|
|Study Completion Date:||August 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Experimental: Ecallantide - Low Dose Regimen
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.
Other Name: DX-88
Experimental: Ecallantide - High Dose Regimen
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.
Other Name: DX-88
Placebo Comparator: Placebo
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.
This was a Phase 2, randomized, double-blind, placebo-controlled, multi-center study designed to assess the efficacy and safety of 2 dose levels of ecallantide compared to placebo in reducing chest tube drainage in participants requiring CPB for primary CABG, single valve repair, or single valve replacement. Participants were randomized in a 3:3:2 ratio to ecallantide high-dose regimen (maximum 91 mg), ecallantide low-dose regimen (maximum 15 mg), or placebo. Randomization was stratified by surgical procedure so that participants undergoing valve replacement would be evenly distributed across treatment arms. Each participant received active drug or placebo administered in stages on the day of the surgical procedure after induction of anesthesia (Day 1).
Participants were screened up to 14 days prior to surgery. Additional study procedures were conducted on Day -1 or 1, peri-operatively, during the immediate postoperative period, and on Days 2, 4, and 7 (or at the time of discharge from the hospital), and between Days 28 and 43 (follow-up).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00448864
|United States, Alabama|
|St. Vincent's Hospital|
|Birmingham, Alabama, United States, 35205|
|United States, Arizona|
|Mayo Clinic Hospital|
|Phoenix, Arizona, United States, 85054|
|United States, Colorado|
|University of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Caritas St. Elizabeth's Medical Center|
|Boston, Massachusetts, United States, 02135|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|SUNY Upstate Medical University|
|Syracuse, New York, United States, 13210|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Gaston Memorial Hospital|
|Gastonia, North Carolina, United States, 28054|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|Hospital of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|The Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Heart Institute|
|Houston, Texas, United States, 77225|
|Study Director:||Andrew L Sternlicht, MD||Dyax Corp.|