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 metatrial of randomised studies

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 metatrial of randomised studies

Aims 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, U...

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Published in:British journal of clinical pharmacology Vol. 87; no. 8; pp. 3075 - 3091
Main Authors: Haren, Frank M.P., Richardson, Alice, Yoon, Hwan‐Jin, Artigas, Antonio, Laffey, John G., Dixon, Barry, Smith, Roger, Vilaseca, Alicia B., Barbera, Ruben A., Ismail, Tarek I., Mahrous, Rabab S., Badr, Mohamed, De Nucci, Gilberto, Sverdloff, Carlos, Loon, Lex M., Camprubi‐Rimblas, Marta, Cosgrave, David W., Smoot, Thomas L., Staas, Sabrina, Sann, Khine, Sas, Caitlin, Belani, Anusha, Hillman, Christopher, Shute, Janis, Carroll, Mary, Wilkinson, Tom, Carroll, Miles, Singh, Dave, Page, Clive
Format: Journal Article
Language:English
Published: England 01-08-2021
Subjects:
acute respiratory distress syndrome
COVID‐19
inhaled heparin
metatrial
nebulised heparin
pandemic
randomised controlled trial
respiratory failure
SARS
SARS‐CoV‐2
unfractionated heparin
COVID-19
SARS-CoV-2
inhaled heparin
acute respiratory distress syndrome
respiratory failure
SARS
randomised controlled trial
metatrial
unfractionated heparin
pandemic
nebulised heparin
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Summary:Aims 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 anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID‐19 (INHALE‐HEP) metatrial 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 metatrial 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 metatrial 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. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.
Bibliography:PI Statement: The authors confirm that the PI for this paper is Professor Frank M.P. van Haren and that he has direct responsibility for the described metatrial. Metatrial Combined Protocol and Statistical Analysis Plan date and version: 14 December 2020, INHALE‐HEP metatrial version 2.0.
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ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.14714