Cardiac Surgical Procedures, Infant, Low Cardiac Output Syndrome
Conditions
Brief summary
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.
Interventions
DRUGMilrinone
The study intervention is an intravenous infusion of milrinone or placebo.
DRUGNormal saline
The study intervention is an intravenous infusion of milrinone or placebo.
Sponsors
Shanghai Children's Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
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* Ventricular arrhythmia before surgery * Without femoral artery catheter before arriving in the ICU * Consent was withdrawn by participants' parent or guardian.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of intensive care stay. | up to 30 days postoperatively or until ICU discharge. | Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge |
| Length of hospital stay. | up to 30 days postoperatively or until hospital discharge | Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge |
| Duration of mechanical ventilation. | up to 30 days postoperatively or until extubation | Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation |
| 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 | — |
| Number of participants requiring mechanical circulatory support. | up to 30 days postoperatively | eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device |
| Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline. | 36 hours after initiation of study drug | Cerebral and abdominal regional tissue oxygenation will be monitored |
| Number of participants with treatment-related adverse events | 36 hours after initiation of study drug | Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer |
| Number of participants with improvement of ventriculoarterial coupling | 36 hours after initiation of study drug | 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 |
| Change in Vasoactive Inotrope Score. | 36 hours after initiation of study drug | 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) |
Countries
China
Contacts
Primary ContactJihong Huang, MD, PhD
Backup ContactZhuoming Xu, MD, PhD
Outcome results
None listed