Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial
Mark Jones,
Brenda Gannon,
David Winlaw,
Yves d’Udekem,
Simon Erickson,
Paul Young,
Luregn J Schlapbach,
Marino Festa,
Andreas Schibler,
Stephen Brian Horton,
Debbie Amanda Long,
John Beca,
Nelson Alphonso,
Kerry Johnson,
Carmel Delzoppo,
Kim van Loon,
B Gannon,
Jonas Fooken,
Antje Blumenthal,
Warwick Butt,
Steve Horton,
Johnny Millar,
David Buckley,
Taryn Evans,
Claire Sherring,
John Artrip,
Killian O’Shaughnessy,
Rebecca Fletcher,
Simon Byrne,
Sam Barr,
Rae Kelly,
David Andrews,
Deborah Long,
Kerry Johnston,
Carla Zuzak,
Benjamin Anderson,
Kim van Loon,
Nicole J C W van Belle-van Haaren,
Bram van Wijk,
Erik Koomen
Affiliations
Mark Jones
3 Institute for Evidence-based Healthcare, Bond University, Gold Coast, Queensland, Australia
Brenda Gannon
The University of Queensland, Centre for Business and Economics of Health, St Lucia Qld, Queensland, Australia
David Winlaw
Cardiothoracic Surgery, St Vincent`s Hospital, Sydney, New South Wales, Australia
Yves d’Udekem
Department of Cardiac Surgery, Royal Children’s Hospital, Melbourne, Victoria, Australia
Simon Erickson
Paediatric Intensive Care Unit, Perth Children’s Hospital, Nedlands, Western Australia, Australia
Paul Young
15 Intensive Care Department, Wellington Hospital, London, UK
Luregn J Schlapbach
Queensland Children`s Hospital, South Brisbane, Queensland, Australia
Marino Festa
Paediatric Intensive Care Unit, The Children`s Hospital at Westmead, Westmead, New South Wales, Australia
Andreas Schibler
Queensland Children`s Hospital, South Brisbane, Queensland, Australia
Stephen Brian Horton
Cardiac Surgical Unit, Royal Children’s Hospital, Melbourne, Victoria, Australia
Debbie Amanda Long
Paediatric Intensive Care Unit, Queensland Children’s Hospital, Children’s Health Queensland, Brisbane, Queensland, Australia
John Beca
Paediatric Intensive Care Unit, Starship Children`s Hospital, Auckland, New Zealand
Nelson Alphonso
Cardiac Surgery, Queensland Children’s Hospital, Brisbane, Queensland, Australia
Kerry Johnson
Paediatric Critical Care Research Group, Child Health Research Institute, The University of Queensland, Brisbane, Queensland, Australia
Carmel Delzoppo
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Kim van Loon
Division of Anaesthetics, University Medical Center Utrecht, Utrecht, The Netherlands
B Gannon
2Mater Research Institute Chair in Health Economics, Centre for Business and Economics of Health, Brisbane, Australia
Jonas Fooken
Centre for the Business and Economics of Health, The University of Queensland, Brisbane, Queensland, Australia
Antje Blumenthal
The Infection and Inflammation Group, The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
Warwick Butt
Clinical Sciences, Murdoch Children`s Research Institute, Parkville, Victoria, Australia
Steve Horton
Johnny Millar
2 Department of Critical Care, The University of Melbourne—Parkville Campus, Melbourne, Victoria, Australia
David Buckley
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
Taryn Evans
Claire Sherring
Paediatric Intensive Care Unit, Starship Children`s Hospital, Auckland, New Zealand
John Artrip
Killian O’Shaughnessy
Rebecca Fletcher
Simon Byrne
Sam Barr
Rae Kelly
David Andrews
Department of Cardiothoracic Surgery, Perth Children`s Hospital, Nedlands, Western Australia, Australia
Deborah Long
Kerry Johnston
Carla Zuzak
Benjamin Anderson
Kim van Loon
Nicole J C W van Belle-van Haaren
Bram van Wijk
Erik Koomen
Department of Paediatric Intensive Care, University Medical Centre Utrecht/Wilhelmina Children’s Hospital, Utrecht, The Netherlands
Introduction Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol.Methods and analysis The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery.Ethics and dissemination The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial registration number ACTRN12617000821392
