| Title: |
Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial |
| Authors: |
Dixon, B; Smith, RJ; Campbell, DJ; Moran, JL; Doig, GS; Rechnitzer, T; MacIsaac, CM; Simpson, N; van Haren, FMP; Ghosh, AN; Gupta, S; Broadfield, EJC; Crozier, TME; French, C; Santamaria, JD |
| Publisher Information: |
ELSEVIER SCI LTD |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
BACKGROUND: Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS: The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2213-2600 |
| Relation: |
https://hdl.handle.net/11343/259972 |
| Availability: |
https://hdl.handle.net/11343/259972 |
| Accession Number: |
edsbas.75160BD7 |
| Database: |
BASE |