Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants

Study Overview
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Brief Summary
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This randomized, multi-center, double-blinded, placebo-controlled study is designed to evaluate the efficacy and safety of milrinone compared with placebo in participants after corrective surgery for congenital heart disease. Participants will be randomized in a 1:1 ratio within 90 minutes after arriving in the intensive care unit (ICU), to receive either intravenous milrinone or placebo for 36 hours. Participants will be stratified according Vasoactive Inotrope Score after arriving in the ICU.

Official Title
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Prophylactic Milrinone Infusion for the Prevention Low Cardiac Output Syndrome After Corrective Surgery for Congenital Heart Disease in Infants: A Randomized, Multi-center, Double-blinded, Placebo-controlled Study

Conditions
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Infant, Low Cardiac Output Syndrome, Cardiac Surgical Procedures

Intervention / Treatment
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* Drug: Milrinone
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age younger than 12 months Without pre-operative low cardiac output syndrome Bi-ventricular repair of congenital heart disease involving cardiopulmonary bypass Informed consent obtained from each participant's parent or guardian Exclusion Criteria: A body weight <2 kg Prematurity (birth <36 weeks postconceptual age) Renal dysfunction ( Creatinine>1.5mg/dL 48 hours before surgery) Low cardiac output syndrome or hypotension on arrival to ICU from OR Cardiopulmonary resuscitation before surgery Platelet count<80,000/mm3 before surgery Left ventricular outflow tract obstruction before surgery Ventricular arrhythmia before surgery Without femoral artery catheter before arriving in the ICU Consent was withdrawn by participants' parent or guardian.

Ages Eligible for Study
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Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: milrinone<br>milrinone milrinone will be administered intravenously at a rate of 0.75ug/kg/min for 35 hours, and baseline catecholamines will be administered at the discretion of the physician. | Drug: Milrinone<br>* The study intervention is an intravenous infusion of milrinone or placebo.<br>* Other names: Milrinone Lactate;|
| Placebo Comparator: normal saline<br>placebo placebo (normal saline) will be administered intravenously for 35 hours, and baseline catecholamines will be administered at the discretion of the physician. | Drug: Normal saline<br>* The study intervention is an intravenous infusion of milrinone or placebo.<br>* Other names: Normal Saline 0.9% Infusion Solution Bag;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants died within 30 days postoperatively |  | up to 30 days postoperatively | 
| Number of participants developed low cardiac output syndrome within the first 36 hours after initiation of study drug | Low cardiac output syndrome was defined as the following: clinical signs or symptoms (eg, tachycardia, oliguria, poor perfusion, or cardiac arrest) with or without a widened arterial-mixed venous oxygen saturation difference or metabolic acidosis; mechanical support of the circulation (eg, extracorporeal life support, ventricular assist device), a cardiac index determined by Pulse indicator continuous cardiac output (PiCCO) of <2.2 L/min/m2 | 36 hours after initiation of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants developed low cardiac output syndrome in the interval between 36 hours after initiation of study drug and the final Follow up. Cardiac index will be determined by Doppler echocardiography |  | up to 30 days postoperatively | 
| Change in Vasoactive Inotrope Score. | Vasoactive Inotrope Score=100*Epinephrine dose (ug/kg/min)+100*Norepinephrine dose (ug/kg/min)+10*Dopamine dose (ug/kg/min)+10*Dobutamine dose (ug/kg/min) +10,000*Vasopressin dose (units/kg/min) +10*Milrinone dose (ug/kg/min) | 36 hours after initiation of study drug | 
| Length of intensive care stay. | Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge | up to 30 days postoperatively or until ICU discharge. | 
| Length of hospital stay. | Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge | up to 30 days postoperatively or until hospital discharge | 
| Duration of mechanical ventilation. | Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation | up to 30 days postoperatively or until extubation | 
| Number of participants with improvement of ventriculoarterial coupling | ventriculoarterial coupling improvement will be assessed by means of ventriculoarterial coupling values shift closer to 1. ventriculoarterial coupling will be obtained as : (1-EF)/EF | 36 hours after initiation of study drug | 
| Number of participants requiring mechanical circulatory support. | eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device | up to 30 days postoperatively | 
| Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline. | Cerebral and abdominal regional tissue oxygenation will be monitored | 36 hours after initiation of study drug | 
| Number of participants with treatment-related adverse events | Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer | 36 hours after initiation of study drug |