INHALE d nebulised unfractionated HEP arin 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
Authors:
- Professor Frank M.P. van Haren, MD PhD FCICM1,2
- Associate Professor Alice Richardson, MStats PhD3
- Associate Professor Hwan-Jin Yoon, PhD3
- Professor Antonio Artigas, MD PhD4
- Professor John G. Laffey, MD MA, FCAI, FJFICMI5,6
- Dr Barry Dixon, MD PhD FCICM7
- Mr Roger Smith, MPH7
- Dr Alicia B Vilaseca8
- Ruben A Barbera8
- Dr Tarek I. Ismail9
- Dr Rabab S. Mahrous10
- Dr Mohamed Badr11
- Professor Gilberto DeNucci, MD BPharm PhD12,13
- Carlos Sverdloff, BPharm MSc12
- Lex M van Loon, PhD1
- Marta Camprubi-Rimblas, PhD4
- Dr David W. Cosgrave6
- Thomas L. Smoot, PharmD BCPS14
- Sabrina Staas, PharmD14
- Khine Sann, MD14
- Caitlin Sas, PharmD14
- Anusha Belani, MD14
- Christopher Hillman, CRNP14
- Professor Janis Shute, PhD15
- Dr Mary Carroll, MD16
- Professor Tom Wilkinson, MBBS PhD16
- Professor Miles Carroll, PhD17
- Professor Dave Singh, MD18
- Professor Clive Page OBE PhD19
Authors’ Affiliations
- Australian National University, College of Health and Medicine,
Canberra, Australia
- University of Canberra, Faculty of Health, Canberra, Australia
- Statistical Consulting Unit, Australian National University, Canberra,
Australia
- Critical Center, Corporació Universitaria Sanitaria Parc Tauli, CIBER
Enfermedades Respiratorias, Autonomous University of Barcelona,
Sabadell, Spain
- Anaesthesia and Intensive Care Medicine, School of Medicine, and
Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research
in Medical Devices, Biomedical Sciences Building, National University
of Ireland Galway, Galway, Ireland
- Department of Anaesthesia, University Hospital Galway, Saolta Hospital
Group, Ireland
- Department of Critical Care Medicine, St Vincent’s Hospital,
Melbourne, Australia
- Service of Haematology and Haemostasis, San Camilo Clinic, Buenos
Aires, Argentina
- Department of Anaesthesia and Surgical Intensive Care, Faculty of
Medicine, Helwan University, Cairo, Egypt
- Department of Anaesthesia and Surgical Intensive Care, Faculty of
Medicine, Alexandria University, Alexandria, Egypt
- Department of Critical Care Medicine, Faculty of Medicine, Helwan
University, Cairo, Egypt
- Department of Pharmacology, Faculty of Medical Sciences, University of
Campinas, Campinas, Brazil
- Department of Pharmacology, Institute of Biomedical Sciences,
University of São Paulo, Brazil
- Frederick Memorial Hospital, Frederick, Maryland, USA
- School of Pharmacy and Biomedical Science, University of Portsmouth,
Portsmouth, United Kingdom
- Department of Respiratory Medicine, University of Southampton,
Southampton, United Kingdom
- National Infection Service, Public Health England, Porton Down, United
Kingdom
- Medicines Evaluation Unit, University of Manchester, Manchester,
United Kingdom
- Sackler Institute of Pulmonary Pharmacology, King’s College London
Corresponding author: Frank van Haren,frank.vanharen@anu.edu.au
Authors’ contributions: Chief Investigator FvH drafted the manuscript
with advice from senior statisticians AR and HJY. All authors
contributed to revision and finalisation of the manuscript. All authors
read and approved the final draft for submission.
Meta-trial Combined Protocol and Statistical Analysis Plan date
and version : 14 December 2020, INHALE-HEP meta-trial version 2.0
Sponsor meta-trial: INHALE-HEP Collaborative Research Group
(CRG). Each individual investigator of every contributing trial is a
member of the INHALE-HEP CRG.
Role sponsor: The INHALE-HEP CRG’s executive committee is
responsible for the meta-trial’s study design; collection, management,
analysis, and interpretation of data; writing of the report; and the
decision to submit the report for publication. Investigators from
individual trials have ownership of their trial data. A collaboration
and data sharing agreement between investigators facilitates and governs
the collecting and analysing of de-identified individual patient data
from individual trials and sets out eligibility for authorship.