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INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and Statistical Analysis Plan for an investigator-initiated international meta-trial of randomised studies
  • +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:[email protected]

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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

Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) meta-trial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the meta-trial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. Analysis We use a Bayesian approach to monitoring, followed by 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. Trial registration, ethics and dissemination The meta-trial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board.
14 Dec 2020Submitted to British Journal of Clinical Pharmacology
15 Dec 2020Assigned to Editor
15 Dec 2020Submission Checks Completed
19 Dec 2020Editorial Decision: Accept