The investigators present a randomised open label phase Ib/IIa trial of nebulised unfractionated heparin to evaluate the effect of nebulised unfractionated heparin on the procoagulant response in ICU patients with SARS-CoV-2 requiring advanced respiratory support. As this is one of the first studies of nebulised heparin in COVID 19 lung disease the investigators will assess safety as a co-primary outcome.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days
University Hospital Galway
Galway, Ireland
D-dimer profile
Effect of nebulised heparin on d-dimer profile, assessed via d-dimer AUC and via a mixed effects model, with data collected on days 1, 3, 5 and 10.
Time frame: Up to day 10.
Frequenccy of Severe Adverse Outcomes
Safety of nebulised heparin delivered by aerogen solo nebuliser in patients with COVID-19 induced severe respiratory failure, as measured by the incidence of severe adverse events.
Time frame: Up to day 60
Oxygenation Index
Determine the impact of nebulised heparin on oxygenation index
Time frame: Up to day 10
Indices of Inflammation
Effect of nebulised heparin on indices of inflammation (Interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1), C-reactive protein, procalcitonin, Ferritin,) will be assessed (AUC on days 1, 3, 5 and 10)
Time frame: Up to day 10
Ratios of Indices of Inflammation
Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.
Time frame: Up to day 10
Indices of Coagulation
Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).
Time frame: Up to day 10
Quasi-Static Lung Compliance
Determine the effect of nebulised heparin on Quasi-Static Lung Compliance (i.e. tidal volume/(Plateau pressure-PEEP) measured on days 1,3,5,10.
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Time frame: Up to day 10
Time to separation from advanced respiratory support
Time to separation from advanced respiratory support, where non survivors are treated as though not separated from advanced respiratory support.
Time frame: Up to day 28
Number treated with neuromuscular blockers
Number treated with neuromuscular blockers instituted after enrolment
Time frame: Up to day 10
Number treated with Prone positioning
Number treated with prone positioning instituted after enrolment
Time frame: Up to day 10
Number treated with extra-corporeal membrane oxygenation
Number treated with extra-corporeal membrane oxygenation instituted after enrolment
Time frame: Up to day 10
Number requiring Tracheostomy
Number tracheotomised
Time frame: Up to day 28
Time to separation from invasive ventilation among survivors
Time to separation from invasive ventilation among survivors
Time frame: Up to day 28
Discharge to ward
Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care
Time frame: Up to day 28
Discharge to ward in survivors
Time to discharge from the ICU to day 28, among survivors
Time frame: Up to day 28
Patient Survival
Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60
Time frame: Up to day 60
Number of patients residing at home or in a community setting at day 60
Number residing at home or in a community setting at day 60
Time frame: Up to day 60
Number of surviving patients residing at home or in a community
Number residing at home or in a community setting at day 60, among survivors
Time frame: Up to day 60
Ventilatory ratio
Effect of nebulised heparin on ventilatory ratio measured every 6 hours
Time frame: Up to day 10
Number treated with awake prone positioning
Number of patients treated with awake prone positioning
Time frame: Up to day 10