Clinical trial NCT00448864
Conditions: Blood Loss, Surgical
Sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Start date: 2007-05-01; Completion date: 2008-08-01
Enrollment: 75 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
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).

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Ecallantide intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents: