Evidence map›Paper›PMID 41181828›Full record

ArticleEClinicalMedicine2025

Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies.

Frank M P van Haren, Sarah J Valle, Ary Serpa Neto, Marcus J Schultz, John G Laffey, Antonio Artigas, Barry Dixon, Alicia B Vilaseca, Ruben A Barbera, Tarek I Ismail and 30 more

Registry-linked trialAbstract read
In one paragraph

Article in EClinicalMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04635241 (INHALEd Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 Meta-trial), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04635241 phase2 / phase3completednot on this map

INHALEd Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 Meta-trial

TypeinterventionalSponsorAustralian National UniversityRan2020 to 2025Enrolled485ConditionsCovid19ArmsUnfractionated heparin
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Frank M P van HarenAustralian National University, College of Health and Medicine, Canberra, Australia.
Sarah J ValleIntensive Care Unit, St George Hospital, Sydney, Australia.
Ary Serpa NetoAustralian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
Marcus J SchultzDepartment of Intensive Care, Amsterdam UMC, Amsterdam, the Netherlands.
John G LaffeyAnaesthesia and Intensive Care Medicine, School of Medicine, University of Galway, Galway, Ireland.
Antonio ArtigasCritical Care Center, Corporació Sanitaria Universitaria Parc Tauli, Institut d'Investigació i Innovació Parc Tauli (I3PT CERCA), CIBER Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain.
Barry DixonDepartment of Critical Care Medicine, St Vincent's Hospital, Melbourne, Australia.
Alicia B VilasecaService of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, Argentina.
Ruben A BarberaService of Haematology and Haemostasis, San Camilo Clinic, Buenos Aires, Argentina.
Tarek I IsmailDepartment of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, Helwan University, Cairo, Egypt.
Rabab S MahrousDepartment of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Mohamed BadrDepartment of Critical Care Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt.
Gilberto DeNucciDepartment of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
Carlos SverdloffDepartment of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
Marta Camprubi-RimblasCritical Care Center, Corporació Sanitaria Universitaria Parc Tauli, Institut d'Investigació i Innovació Parc Tauli (I3PT CERCA), CIBER Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain.
David W CosgraveAnaesthesia and Intensive Care Medicine, School of Medicine, University of Galway, Galway, Ireland.
Bairbre McNicholasAnaesthesia and Intensive Care Medicine, School of Medicine, University of Galway, Galway, Ireland.
Catriona CodyDepartment of Anaesthesia and Intensive Care Medicine, Connolly Memorial Hospital Blanchardstown, Dublin, Ireland.
Gerard CurleyDepartment of Anaesthesia and Intensive Care Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Thomas L SmootFrederick Memorial Hospital, Frederick, MD, USA.
Sabrina StaasFrederick Memorial Hospital, Frederick, MD, USA.
Khine SannFrederick Memorial Hospital, Frederick, MD, USA.
Caitlin SasFrederick Memorial Hospital, Frederick, MD, USA.
Anusha BelaniFrederick Memorial Hospital, Frederick, MD, USA.
Christopher HillmanFrederick Memorial Hospital, Frederick, MD, USA.
Sidharta Kusuma ManggalaRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Dita AditianingsihRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Adhrie SugiartoRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Mira YuliantiRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Herikurniawan HerikurniawanRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Robert SintoRSUP Dr Cipto Mangunkusumo, Jakarta, Indonesia.
Aino Nindya AuerkariRS Universitas Indonesia, Depok, Indonesia.
Septian Adi PermanaRSUD Dr Moewardi, Surakarta, Indonesia.
Ashley WoodcockDivision of Immunology, Immunity to Infection & Respiratory Medicine, University of Manchester, Manchester, United Kingdom.
Mary CarrollDepartment of Respiratory Medicine, University of Southampton, Southampton, United Kingdom.
Tom WilkinsonDepartment of Respiratory Medicine, University of Southampton, Southampton, United Kingdom.
Dave SinghMedicines Evaluation Unit, University of Manchester, Manchester, United Kingdom.
Janis Kay ShuteSchool of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, United Kingdom.
Miles CarrollCentre for Human Genetics & Pandemic Sciences Institute, Nuffield Dept of Medicine, University of Oxford, Oxford, United Kingdom.
Clive PageUnit of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Inhaled nebulised unfractionated heparin (UFH) has a strong rationale as a treatment for severe respiratory infections, including COVID-19, due to its antiviral, anti-inflammatory, and anti-coagulant properties, which may prevent viral entry, lung injury progression, and pulmonary thrombosis. We aimed to evaluate the efficacy of inhaled nebulised UFH to prevent intubation or death in hospitalised COVID-19 patients. Methods: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised clinical studies, adult hospitalised but not intubated COVID-19 patients were randomly assigned to inhaled nebulised UFH on top of standard of care or standard of care alone. The dose and method of nebulisation was specific to each study. The primary outcome was intubation or death, assessed at the longest follow-up after randomisation. The meta-trial was registered at ClinicalTrials.gov ID NCT04635241. Findings: Between June 2020 and December 2022, 478 patients from 10 hospitals in six countries (Argentina, Brazil, Egypt, Indonesia, Ireland and USA) were enrolled. The odds ratio (OR) for intubation or death was 0.43 (0.26-0.73, p = 0.001); the OR for in-hospital mortality was 0.26 (0.13-0.54, p < 0.001) with inhaled nebulised UFH compared to standard of care alone. There were no safety issues reported, including no instances of pulmonary or systemic bleeding in the nebulised UFH group. Interpretation: In patients hospitalised but not intubated for COVID-19, inhaled nebulised UFH prevented intubation and reduced mortality, without causing pulmonary or systemic bleeding. Funding: The Sponsor of the meta-trial was the INHALE-HEP Collaborative Research Group (CRG); investigators of each contributing study were members of the INHALE-HEP CRG. No funding was received for the meta-trial. The Brazilian study was funded by The J.R. Moulton Charity Trust. The Irish study was funded by a Grant from Science Foundation Ireland to Cúram, the SFI's Centre for Research in Medical Devices (Research Centre Award Reference: 13/RC/2073).

Indexed as

ARDSCOVID-19Inhaled heparinIntubationMeta-trialMortalityNebulised heparinPandemicRandomised trialRespiratory failureSARS-CoV-2Unfractionated heparin

Identifiers

PMID41181828
PMCPMC12572793

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.