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Statistical analysis plan for the INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) meta-trial
  • +26
  • Frank van Haren,
  • Alice Richardson,
  • Jin Yoon,
  • Antonio Artigas,
  • John Laffey,
  • Barry Dixon,
  • Roger Smith,
  • Alicia Vilaseca,
  • Ruben Barbera,
  • Tarek Ismail,
  • Rabab Mahrous,
  • Mohamed Badr,
  • Gilberto De Nucci,
  • Carlos Sverdloff,
  • Lex van Loon,
  • Marta Camprubi-Rimblas,
  • David Cosgrave,
  • Thomas Smoot,
  • Sabrina Staas,
  • Khine Sann,
  • Caitlin Sas,
  • Anusha Belani,
  • Christopher Hillman,
  • Janis Shute,
  • Mary Carroll,
  • Tom Wilkinson,
  • Miles Carroll,
  • Dave Singh,
  • Clive Page
Frank van Haren
Australian National University

Corresponding Author:frank.vanharen@anu.edu.au

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Alice Richardson
Australian National University
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Jin Yoon
Australian National University
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Antonio Artigas
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John Laffey
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Barry Dixon
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Roger Smith
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Alicia Vilaseca
SAN CAMILO CLINIC BUENOS AIRES
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Ruben Barbera
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Tarek Ismail
Helwan University Faculty of Medicine
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Rabab Mahrous
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Mohamed Badr
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Gilberto De Nucci
University of Sao Paulo
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Carlos Sverdloff
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Lex van Loon
Australian National University
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Marta Camprubi-Rimblas
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David Cosgrave
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Thomas Smoot
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Sabrina Staas
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Khine Sann
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Caitlin Sas
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Anusha Belani
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Christopher Hillman
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Janis Shute
University of Portsmouth
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Mary Carroll
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Tom Wilkinson
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Miles Carroll
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Dave Singh
University Of Manchester
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Clive Page
Kings College London
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Abstract

The INHALE-HEP meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies, to evaluate whether inhaled nebulised UFH in hospitalised patients with COVID-19 who do not require immediate invasive mechanical ventilation, significantly reduces intubation (or death, for patients who died before intubation) at day 28 compared to standard care alone. Objective: In keeping with best practice and with the published protocol, a pre-specified statistical analysis plan has been described and made public before completion of patient recruitment and data collection into the INHALE-HEP meta-trial. Methods: Our statistical analysis plan was designed by the INHALE-HEP executive committee and statisticians and approved by the INHALE-HEP steering committee. We reviewed the data collected as specified in the meta-trial protocol and collected in individual contributing studies. We present information pertaining to data collection, pre-specified subgroups, and study outcomes. Primary and secondary outcomes are defined, and additional subgroup analyses of pre-defined variables are described. Results: We have described our methods for presenting the trial profile and baseline characteristics, as well as our Bayesian approach to monitoring and meta-analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Conclusion: To minimise analytical bias, we have developed a statistical analysis plan and made this available to the public domain before completion of patient recruitment and data collection into the INHALE-HEP meta-trial.