Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants

• ClinicalTrials.gov Identifier: NCT03823781
• Recruitment Status: Unknown
• First Posted: January 30, 2019
• Last Update Posted: January 30, 2019
• Sponsor: Shanghai Children's Medical Center
• Information provided by (Responsible Party): Shanghai Children's Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Low Cardiac Output Syndrome; Cardiac Surgical Procedures; Infant	Drug: Milrinone; Drug: Normal saline	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 520 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: February 2019
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: July 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: milrinone; 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; The study intervention is an intravenous infusion of milrinone or placebo.; Other Name: Milrinone Lactate
Placebo Comparator: normal saline; 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; The study intervention is an intravenous infusion of milrinone or placebo.; Other Name: Normal Saline 0.9% Infusion Solution Bag

Outcome Measures

Primary Outcome Measures :

1. Number of participants died within 30 days postoperatively [ Time Frame: up to 30 days postoperatively ]
2. Number of participants developed low cardiac output syndrome within the first 36 hours after initiation of study drug [ Time Frame: 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 Outcome Measures :

1. 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 [ Time Frame: up to 30 days postoperatively ]
2. Change in Vasoactive Inotrope Score. [ Time Frame: 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)
3. Length of intensive care stay. [ Time Frame: 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
4. Length of hospital stay. [ Time Frame: 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
5. Duration of mechanical ventilation. [ Time Frame: 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
6. Number of participants with improvement of ventriculoarterial coupling [ Time Frame: 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
7. Number of participants requiring mechanical circulatory support. [ Time Frame: up to 30 days postoperatively ]
   eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device
8. Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline. [ Time Frame: 36 hours after initiation of study drug ]
   Cerebral and abdominal regional tissue oxygenation will be monitored
9. Number of participants with treatment-related adverse events [ Time Frame: 36 hours after initiation of study drug ]
   Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer

Eligibility Criteria

• Ages Eligible for Study: up to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jihong Huang, MD, PhD; +8618930830766; huangjihong@scmc.com.cn

Contact: Zhuoming Xu, MD, PhD; +8618930830783; xuzhuoming@scmc.com.cn

Locations

China, Shanghai

Shanghai Shanghai Children's Medical Center; Recruiting

Shanghai, Shanghai, China, 200127

Contact: Jihong Huang, MD, PhD +8618930830766 huangjihong@scmc.com.cn

Contact: Chunxiang Li, MD +8618916611383 lichunxiang@scmc.com.cn

Principal Investigator: Huiwen Chen, MD, PhD

Sponsors and Collaborators

Shanghai Children's Medical Center

Investigators

• Study Director: Huiwen Chen, MD, PhD; Department of clinical research, Shanghai children's medical center

More Information

• Responsible Party: Shanghai Children's Medical Center
• ClinicalTrials.gov Identifier: NCT03823781
• Other Study ID Numbers: SCMCIRB-K2018105
• First Posted: January 30, 2019
• Last Update Posted: January 30, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cardiac Output, Low; Syndrome; Disease; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Milrinone; Cardiotonic Agents; Platelet Aggregation Inhibitors; Vasodilator Agents; Phosphodiesterase 3 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs