Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics.
BACKGROUND
Many pediatric patients undergoing cardiac surgery involving cardiopulmonary bypass have a predictable fall in the cardiac index 6 to 18 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 microg/kg intravenous bolus over 60 minutes followed by a 0.25 microg/kg/min infusion for 35 hours), (2) high-dose milrinone (75 microg/kg intravenous bolus over 60 minutes followed by a 0.75 microg/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.
Hoffman
Timothy M
TM
Children's Hospital of Philadelphia, Philadelphia, Pa 19104, USA
Wernovsky
Gil
G
Atz
Andrew M
AM
Bailey
James M
JM
Akbary
Akbar
A
Kocsis
John F
JF
Nelson
David P
DP
Chang
Anthony C
AC
Kulik
Thomas J
TJ
Spray
Thomas L
TL
Wessel
David L
DL
D002303:Cardiac Output, Low / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007223:Infant; D008297:Male; D020105:Milrinone / Q000008:administration & dosage* / Q000009:adverse effects; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D013577:Syndrome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D002316:Cardiotonic Agents; D014665:Vasodilator Agents; D020105:Milrinone