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

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

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Alicia Vilaseca
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Ruben Barbera
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Tarek Ismail
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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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Alice Richardson
Australian National University
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Jin Yoon
Australian National University
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Antonio Artigas
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Marta Camprubi-Rimblas
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John Laffey
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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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Roger Smith
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Barry Dixon
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Clive Page
Kings College London
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Abstract

Introduction Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential for 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 This meta-trial is a prospective collaborative individual patient data meta-analysis of randomised controlled trials and early phase studies. Individual studies are conducted in multiple countries. Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, are randomised to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome is intubation (or death, for patients who died before intubation) at day 28, assessed in a time-to-event analysis. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have specific outcome measures in addition to the core set. Ethics and dissemination: The meta-trial is registered at ClinicalTrials.gov, ID NCT04635241. Results of this study will be shared with the WHO, published in scientific journals and presented at scientific meetings.