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Table 2 Clinical studies of nebulised heparin treatment for acute lung injury

From: Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

Dosage (Timing) Patients n Nebulizer Outcomes Reference
Clinical studies of acute respiratory distress syndrome with nebulised heparin
 50000-400000 IU/day (two days) MV ARDS
Open-label phase 1 trial
16 Aeroneb Pro Nebulizer ↓systemic coagulation
(↓ pulmonary coagulation, 400000 IU)
Dixon et al, 2008 [114]
 25000 IU (every 4h or 6h, max 14 days) > 48h MV
RCT
50 Aeroneb Pro Nebulizer ↓systemic coagulation
↑ Free days MV
Dixon et al, 2010 [100]
 5000 IU (four times a day until cease MV or discharge from the UCI) > 48h MV
Phase 2 RCT
214 Aeroneb Pro Nebulizer = Bandeshe et al, 2016 [115]
 50000 IU (one day) Elective cardiac surgery
RCT
40 Aeroneb Pro Nebulizer ↓ alveolar dead space fraction and tidal volumes Dixon et al, 2016 [101]
 25000 IU (every 6h, 10 days) MV ARDS
RCT
256 Aeroneb Pro Nebulizer ↓Lung injury
↑ 60 day survivors at home
Dixon et al, 2020
(submitted for publication)
Clinical studies of acute respiratory distress syndrome with nebulised heparin and combined with another treatment
 5000 IU combined with N-acetylcysteine and bronchodilator (every 4h for 7 days) Burn patients paediatric
Retrospective
90 (children) NR ↓atelectasis, reintubation and mortality Desai et al, 1999 [116]
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) Burn patients
Retrospective
150 (children/adults) NR = Holt et al, 2008 [117]
 10000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) Burn patients
Retrospective
30 NR ↓ lung injury
↓ mortality
↑ oxygenation
Miller et al, 2009 [118]
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) Burn patients
Retrospective
63 NR = Yip et al, 2011 [119]
 5000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) Burn patients
Retrospective
40 NR = Kashefi et al, 2014 [120]
 10000 IU combined N-acetylcystine and bronchodilator (every 4h for 7 days) Burn patients
Retrospective
72 NR ↑ free days MV McIntire et al, 2017 [121]
 25000 IU (every 4h for 14 days) Burn patients
RCT (terminated, insufficient recruitment of patients and high costs associated with the purchase and blinding of study medication)
160 Aeroneb Pro Nebulizer Not available Glas et al, 2014 [122]
Clinical studies of COVID-19 with nebulised heparin
 25000 IU (every 6h for 10 days) SARS CoV 2 infection, on MV RCT
ACTRN: 12620000517976
Aeroneb Pro Nebulizer On-going Dixon et al, 2020 [123]
 25000 IU (every 6h up to 21 days) SARS CoV 2 infection, pre-ICU RCT
EudraCT: 2020-001736-95
Aeroneb Pro Nebulizer On-going ACCORD-2 (NHS UK)
  1. ↓: reduced, ↑: increased, =: equal, MV mechanical ventilation, RCT randomized controlled trial, NR not reported