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

Autores de I3PT

• Antoni Artigas Raventós

  Autor

• Marta Camprubí Rimblas

  Autor

Participantes ajenos a I3PT

• Van Haren, FMP
• Valle, SJ
• Neto, AS
• Schultz, MJ
• Laffey, JG
• Dixon, B
• Vilaseca, AB
• Barbera, RA
• Ismail, TI
• Mahrous, RS
• Badr, M
• Denucci, G
• Sverdloff, C
• Cosgrave, DW
• McNicholas, B
• Cody, C
• Curley, G
• Smoot, TL
• Staas, S
• Sann, K
• Sas, C
• Belani, A
• Hillman, C
• Manggala, SK
• Aditianingsih, D
• Sugiarto, A
• Yulianti, M
• Herikurniawan, H
• Sinto, R
• Auerkari, AN
• Permana, SA
• Woodcock, A
• Carroll, M
• Wilkinson, T
• Singh, D
• Shute, JK
• Carroll, M
• Page, C

Grupos de Investigación

• Investigació traslacional en el pacient crític

  

  Investigador

  Josefina López Aguilar

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.

Keywords

• COVID-19; ARDS; Inhaled heparin; Nebulised heparin; Unfractionated heparin; SARS-CoV-2; Respiratory failure; Pandemic; Randomised trial; Meta-trial; Intubation; Mortality