ANZICS CTG Endorsed Study
Nitric oxide on cardio pulmonary bypass in congenital heart disease
Congenital heart disease occurs in about 1% of all children and the majority of these children will require corrective or palliative cardiac surgery at some stage during childhood. In Australia and New Zealand, the cardiac surgical and intensive care mortality of children is low. However, morbidity and long term outcomes remain a major concern in these children. In the hours immediately following heart surgery on cardiopulmonary bypass (CPB), children frequently suffer from low cardiac output syndrome (LCOS). Low cardiac output results in inadequate organ blood flow (hypoperfusion) resulting in organ dysfunction and injury. The most common complications are renal failure, liver failure and most importantly neurological injury. Mortality, morbidity, and long-term functional outcomes are directly related to LCOS.
A recent randomised controlled pilot study from our group showed that the delivery of gaseous nitric oxide (NO) to the CPB circuit for children undergoing cardiac surgery for infants with congenital heart defects resulted in less LCOS, and an improved postoperative recovery with shorter duration of ventilation. In order to confirm these preliminary findings, we aim to investigate, in a multicentre randomised controlled trial, if NO on cardiopulmonary bypass improves survival free of ventilation. The study will investigate as well the impact of the intervention on mortality, LCOS, and need for postoperative extracorporeal life support, PICU length of stay, costs, and host inflammation.
This study is supported by the well-experienced paediatric intensive care research and cardiac surgical network across Australia and New Zealand. The investigators have substantial track records in multi-centre trials and this study will represent the first population based interventional trial in cardiac surgical and paediatric intensive care patients.
Luregn Schlapbach & Andreas Schibler (Co-Chairs), Debbie Long (Project Manager), John Beca, Warwick Butt, Simon Erickson, Marino Festa, Steve Horton, Mark Jones, and Paul Young.
Mater Research Institute, The University of Queensland, Brisbane, Queensland
Diamantina Institute, UQ, Brisbane: Antje Blumenthal
Public Health, UQ, Brisbane: Mark Jones
Health Economist, UQ, Brisbane: Brenda Gannon, Jonas Fooken
Utrecht Medical Center, the Netherlands: Kim van der Loon
Children’s Health Foundation QLD – Project Grant – $274,000
HeartKids – Project Grant – $50,000
NHMRC Project Grant – $1,878,889.40
Project Status as of June 2018
All five ANZ sites are currently recruiting. LCCH started in July 2017, RCHM in October 2017, Perth in February 2018, Auckland in March 2018, Westmead in April 2018. The weekly recruitment numbers have increased from 4-6/week to currently 10-12/week. The target number is 13 recruitments per week.
Site visits have occurred except Perth, where, due to the hospital move to the new children’s hospital (June 2018), the local team preferred to postpone the site visit to later in 2018.
Monitoring using primary source verification has been tested and implemented at LCCH and is in progress at the other sites.
No major adverse events considered to be likely related to the intervention have occurred.
Paul Young was invited to join the study team as a trial expert.
The sample size calculation has been refined using the raw pilot study data and revised assumptions on VFD distribution based on Paul Young’s advice. The final sample size has been revised to 1320.
The study protocol has undergone revision and is being finalized to be submitted to CTG prior to publication.
Luregn Schlapbach (email)