Browsing by Author "van Haren F.M.P."

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    Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies
    (2022-07-01) van Haren F.M.P.; Laffey J.G.; Artigas A.; Page C.; Schultz M.J.; Cosgrave D.; McNicholas B.; Smoot T.L.; Nunes Q.; Richardson A.; Yoon H.J.; van Loon L.M.; Ghosh A.; Said S.; Panwar R.; Smith R.; Santamaria J.D.; Dixon B.; Mahidol University
    There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. Methods and intervention: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.
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    Defining and subphenotyping ARDS: insights from an international Delphi expert panel
    (2025-01-01) Nasa P.; Bos L.D.; Estenssoro E.; van Haren F.M.P.; Neto A.S.; Rocco P.R.M.; Slutsky A.S.; Schultz M.J.; Nasa P.; Mahidol University
    Although the definition of acute respiratory distress syndrome (ARDS) has undergone numerous revisions aimed at enhancing its diagnostic accuracy and clinical practicality, the usefulness and precision of these definitions remain matters of ongoing discussion. In this Position Paper, we report on a Delphi study to reach a consensus on the conceptual model of ARDS, specifically identifying its defining components within clinical, research, and educational contexts as well as exploring the potential role of subphenotyping. We did a four-round Delphi study, involving experts in ARDS research and management from a diverse range of geoeconomic regions and professional backgrounds. Consensus was achieved for the conceptual model of ARDS; key components to be included for an ARDS definition in the context of research, education, and patient management; and the need for further research in subphenotyping ARDS. Additionally, we highlight knowledge gaps and research priorities that could guide future investigations in this area. Our study builds on previous non-Delphi-based consensus processes (eg, the new global definition of ARDS and recent society-based guidelines) by using a rigorous Delphi method that ensured panellist anonymity and used clear quantitative criteria to mitigate potential peer pressure and group conformity. The findings underscore the need to refine the ARDS definition to better account for the heterogeneity of clinical presentations and underlying pathophysiology, and to improve diagnostic precision, including the use of subphenotyping where appropriate.
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    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
    (2025-10-01) van Haren F.M.P.; Valle S.J.; Neto A.S.; Schultz M.J.; Laffey J.G.; Artigas A.; Dixon B.; Vilaseca A.B.; Barbera R.A.; Ismail T.I.; Mahrous R.S.; Badr M.; DeNucci G.; Sverdloff C.; Camprubi-Rimblas M.; Cosgrave D.W.; McNicholas B.; Cody C.; Curley G.; Smoot T.L.; Staas S.; Sann K.; Sas C.; Belani A.; Hillman C.; Manggala S.K.; Aditianingsih D.; Sugiarto A.; Yulianti M.; Herikurniawan H.; Sinto R.; Auerkari A.N.; Permana S.A.; Woodcock A.; Carroll M.; Wilkinson T.; Singh D.; Shute J.K.; Carroll M.; Page C.; van Haren F.M.P.; Mahidol University
    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 atClinicalTrials.govIDNCT04635241. 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).