Trial Design
Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study

https://doi.org/10.1067/mhj.2002.120305Get rights and content

Abstract

Background Many pediatric patients undergoing cardiac surgery involving cardiopulmonary bypass have a predictable fall in the cardiac index 6 to18 hours after surgery, the so-called low cardiac output syndrome (LCOS). Because patients who have LCOS require more monitoring and support and have a prolonged stay in the intensive care unit, the syndrome is associated with a costly morbidity. Milrinone, a phosphodiesterase III inhibitor, improves cardiac muscle contractile force and vascular muscle relaxation through positive inotropic and vasodilatory effects. The purpose of the Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics (PRIMACORP) study is to evaluate the safety and efficacy of the prophylactic use of milrinone in pediatric patients at high risk for development of LCOS after undergoing cardiac surgery. Methods Patients in the multicenter, randomized, double-blind, placebo-controlled, parallel treatment study will be randomized to 1 of 3 treatment arms: (1) low-dose milrinone (25 μg/kg intravenous bolus over 60 minutes followed by a 0.25 μg/kg/min infusion for 35 hours), (2) high-dose milrinone (75 μg/kg intravenous bolus over 60 minutes followed by a 0.75 μg/kg/min infusion for 35 hours), or (3) placebo. Results The primary end point for efficacy evaluation will be based on a composite variable consisting of death or development of LCOS requiring additional mechanical or pharmacologic support, up to 36 hours after randomization. A 2-sided test with a 0.025 type I error will be used for the primary end point analysis. The PRIMACORP study will enroll a total of 240 patients. Six additional secondary end points will be analyzed. Conclusions The PRIMACORP study will address several questions regarding the safety and efficacy of prophylactic milrinone use in pediatric patients at high risk for development of LCOS after cardiac surgery. (Am Heart J 2002;143:15-21.)

Section snippets

Study organization

The study design and supervision of the PRIMACORP trial is the responsibility of the Steering Committee, Clinical Endpoint Committee, and Data Safety Monitoring Board (DSMB). In addition to the protocol development, the role of the Steering Committee is to provide academic leadership for the overall conduct of the trial, which includes interpreting and disseminating the results. The DSMB is responsible for overseeing the safety of PRIMACORP participants. The Clinical Endpoint Committee, a

Discussion

Because of the strong relationship between a drop in cardiac index and the possibility of cardiac death, it is imperative that LCOS be identified and treated.3 Parr et al4 evaluated 139 infants and small children ≤48 months old for 72 hours after intracardiac surgery. The mortality rate was 19.4% (n = 27), and more than half the deaths were caused by acute cardiac failure and were associated with a low cardiac index (<2.0 L/min/m2). Wernovsky et al7 evaluated 171 pediatric patients <3 months

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    Reprint requests: Gil Wernovsky, MD, Children's Hospital of Philadelphia, Division of Cardiology, 34th and Civic Center Boulevard, Philadelphia, PA 19104. E-mail: [email protected]

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