Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve recovery in infants with congenital heart defects (NITRIC) trial

Kristen S. Gibbons*, Luregn J. Schlapbach, Stephen B. Horton, Debbie A. Long, John Beca, Simon Erickson, Marino Festa, Yves D’udekem, Nelson Alphonso, David Winlaw, Kerry Johnson, Carmel Delzoppo, Kim van Loon, Brenda Gannon, Jonas Fooken, Antje Blumenthal, Paul J. Young, Warwick Butt, Andreas Schibler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392.

Original languageEnglish (US)
Pages (from-to)47-58
Number of pages12
JournalCritical Care and Resuscitation
Volume23
Issue number1
DOIs
StatePublished - Mar 2021

Funding

Acknowledgements: This work was supported by grants from the Heart Kids Foundation, Australia; the Children’s Health Foundation, Australia; and by a grant from the National Health and Medical Research Council (NHMRC), Australia (GNT1140322). Yves d’Udekem and Luregn Schlapbach hold NHMRC Clinical Practitioner Fellowships and Andreas Schibler holds a Medical Research Future Fund Practitioner Fellowship. Simon Erickson is supported by a grant from the Perth Children’s Hospital Foundation. The Victorian Government’s Operational Infrastructure Support Program supported this research project. Paul Young holds a Clinical Practitioner Fellowship from the Health Research Council of New Zealand. The funding sources had no involvement in study design, analyses, or interpretation of the results. Mallinckrodt Pharmaceuticals is providing nitric oxide delivery devices to Australian and New Zealand study sites, and The Netherlands site has a NO-A nitric oxide delivery system on loan from EKU Elektronik during the study period. Neither company have any involvement in study design, conduct or analyses. This work was supported by grants from the Heart Kids Foundation, Australia; the Children?s Health Foundation, Australia; and by a grant from the National Health and Medical Research Council (NHMRC), Australia (GNT1140322). Yves d?Udekem and Luregn Schlapbach hold NHMRC Clinical Practitioner Fellowships and Andreas Schibler holds a Medical Research Future Fund Practitioner Fellowship. Simon Erickson is supported by a grant from the Perth Children?s Hospital Foundation. The Victorian Government?s Operational Infrastructure Support Program supported this research project. Paul Young holds a Clinical Practitioner Fellowship from the Health Research Council of New Zealand. The funding sources had no involvement in study design, analyses, or interpretation of the results. Mallinckrodt Pharmaceuticals is providing nitric oxide delivery devices to Australian and New Zealand study sites, and The Netherlands site has a NO-A nitric oxide delivery system on loan from EKU Elektronik during the study period. Neither company have any involvement in study design, conduct or analyses.

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine
  • Anesthesiology and Pain Medicine

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