PMID- 33377218
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20210806
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 87
IP  - 8
DP  - 2021 Aug
TI  - 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.
PG  - 3075-3091
LID - 10.1111/bcp.14714 [doi]
AB  - 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      or withdrawn.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.
CI  - (c) 2020 British Pharmacological Society.
FAU - van Haren, Frank M P
AU  - van Haren FMP
AUID- ORCID: 0000-0001-8037-4229
AD  - Australian National University, College of Health and Medicine, Canberra, 
      Australia.
AD  - Faculty of Health, University of Canberra, Canberra, Australia.
FAU - Richardson, Alice
AU  - Richardson A
AD  - Statistical Consulting Unit, Australian National University, Canberra, Australia.
FAU - Yoon, Hwan-Jin
AU  - Yoon HJ
AD  - Statistical Consulting Unit, Australian National University, Canberra, Australia.
FAU - Artigas, Antonio
AU  - Artigas A
AD  - Critical Center, Corporacio Universitaria Sanitaria Parc Tauli, CIBER 
      Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain.
FAU - Laffey, John G
AU  - Laffey JG
AD  - Anaesthesia and Intensive Care Medicine, School of Medicine, and Regenerative 
      Medicine Institute (REMEDI) at CURAM Centre for Research in Medical Devices, 
      Biomedical Sciences Building, National University of Ireland Galway, Galway, 
      Ireland.
AD  - Department of Anaesthesia, University Hospital Galway, Saolta Hospital Group, 
      Ireland.
FAU - Dixon, Barry
AU  - Dixon B
AD  - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, 
      Australia.
FAU - Smith, Roger
AU  - Smith R
AD  - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, 
      Australia.
FAU - Vilaseca, Alicia B
AU  - Vilaseca AB
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Barbera, Ruben A
AU  - Barbera RA
AD  - Service of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, 
      Argentina.
FAU - Ismail, Tarek I
AU  - Ismail TI
AD  - Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, 
      Helwan University, Cairo, Egypt.
FAU - Mahrous, Rabab S
AU  - Mahrous RS
AD  - Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, 
      Alexandria University, Alexandria, Egypt.
FAU - Badr, Mohamed
AU  - Badr M
AD  - Department of Critical Care Medicine, Faculty of Medicine, Helwan University, 
      Cairo, Egypt.
FAU - De Nucci, Gilberto
AU  - De Nucci G
AD  - Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, 
      Campinas, Brazil.
AD  - Department of Pharmacology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Brazil.
FAU - Sverdloff, Carlos
AU  - Sverdloff C
AD  - Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, 
      Campinas, Brazil.
FAU - van Loon, Lex M
AU  - van Loon LM
AD  - Australian National University, College of Health and Medicine, Canberra, 
      Australia.
FAU - Camprubi-Rimblas, Marta
AU  - Camprubi-Rimblas M
AD  - Critical Center, Corporacio Universitaria Sanitaria Parc Tauli, CIBER 
      Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain.
FAU - Cosgrave, David W
AU  - Cosgrave DW
AD  - Department of Anaesthesia, University Hospital Galway, Saolta Hospital Group, 
      Ireland.
FAU - Smoot, Thomas L
AU  - Smoot TL
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Staas, Sabrina
AU  - Staas S
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Sann, Khine
AU  - Sann K
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Sas, Caitlin
AU  - Sas C
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Belani, Anusha
AU  - Belani A
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Hillman, Christopher
AU  - Hillman C
AD  - Frederick Memorial Hospital, Frederick, Maryland, USA.
FAU - Shute, Janis
AU  - Shute J
AD  - School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, 
      UK.
FAU - Carroll, Mary
AU  - Carroll M
AD  - Department of Respiratory Medicine, University of Southampton, Southampton, UK.
FAU - Wilkinson, Tom
AU  - Wilkinson T
AD  - Department of Respiratory Medicine, University of Southampton, Southampton, UK.
FAU - Carroll, Miles
AU  - Carroll M
AD  - National Infection Service, Public Health England, Porton Down, UK.
FAU - Singh, Dave
AU  - Singh D
AD  - Medicines Evaluation Unit, University of Manchester, Manchester, UK.
FAU - Page, Clive
AU  - Page C
AD  - Sackler Institute of Pulmonary Pharmacology, King's College London, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT04635241
PT  - Journal Article
DEP - 20210119
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adult
MH  - Bayes Theorem
MH  - *COVID-19
MH  - *Heparin
MH  - Humans
MH  - Prospective Studies
MH  - SARS-CoV-2
MH  - Treatment Outcome
OTO - NOTNLM
OT  - COVID-19
OT  - SARS
OT  - SARS-CoV-2
OT  - acute respiratory distress syndrome
OT  - inhaled heparin
OT  - metatrial
OT  - nebulised heparin
OT  - pandemic
OT  - randomised controlled trial
OT  - respiratory failure
OT  - unfractionated heparin
EDAT- 2020/12/31 06:00
MHDA- 2021/08/07 06:00
CRDT- 2020/12/30 05:24
PHST- 2020/12/14 00:00 [received]
PHST- 2020/12/19 00:00 [accepted]
PHST- 2020/12/31 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2020/12/30 05:24 [entrez]
AID - 10.1111/bcp.14714 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 
      Jan 19.