ARDS, Human, Covid19, Lung Injury, Acute, Ventilation Perfusion Mismatch
Conditions
Brief summary
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.
Interventions
DRUGNebulised heparin
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days
Sponsors
University College Hospital Galway
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible, a patient must satisfy all these inclusion criteria: 1. Confirmed or suspected COVID-19. Note, if 'suspected', results must be pending or testing intended 2. Ability to obtain informed consent/assent to participate in study 3. Age 18 years or older 4. Requiring high flow nasal oxygen or positive pressure ventilator support or invasive mechanical ventilation for a time period of no greater than 48 hours 5. D-dimers \> 200 ng/ml 6. PaO2 to FIO2 ratio less than or equal to 300 7. Acute opacities on chest imaging affecting at least one lung quadrant. Note 'Acute opacities' do not include effusions, lobar/lung collapse or nodules 8. Currently in a higher level of care area designated for inpatient care of patients where therapies including non-positive pressure ventilatory support can be provided.
Exclusion criteria
To be eligible, a patient must have none of these
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| D-dimer profile | Up to day 10. | 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. |
| Frequenccy of Severe Adverse Outcomes | Up to day 60 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratios of Indices of Inflammation | Up to day 10 | Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed. |
| Indices of Coagulation | Up to day 10 | Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10). |
| Quasi-Static Lung Compliance | Up to day 10 | 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. |
| Time to separation from advanced respiratory support | Up to day 28 | Time to separation from advanced respiratory support, where non survivors are treated as though not separated from advanced respiratory support. |
| Number treated with neuromuscular blockers | Up to day 10 | Number treated with neuromuscular blockers instituted after enrolment |
| Number treated with Prone positioning | Up to day 10 | Number treated with prone positioning instituted after enrolment |
| Number treated with extra-corporeal membrane oxygenation | Up to day 10 | Number treated with extra-corporeal membrane oxygenation instituted after enrolment |
| Number requiring Tracheostomy | Up to day 28 | Number tracheotomised |
| Oxygenation Index | Up to day 10 | Determine the impact of nebulised heparin on oxygenation index |
| Discharge to ward | Up to day 28 | Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care |
| Discharge to ward in survivors | Up to day 28 | Time to discharge from the ICU to day 28, among survivors |
| Patient Survival | Up to day 60 | Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60 |
| Number of patients residing at home or in a community setting at day 60 | Up to day 60 | Number residing at home or in a community setting at day 60 |
| Number of surviving patients residing at home or in a community | Up to day 60 | Number residing at home or in a community setting at day 60, among survivors |
| Ventilatory ratio | Up to day 10 | Effect of nebulised heparin on ventilatory ratio measured every 6 hours |
| Number treated with awake prone positioning | Up to day 10 | Number of patients treated with awake prone positioning |
| Time to separation from invasive ventilation among survivors | Up to day 28 | Time to separation from invasive ventilation among survivors |
| Indices of Inflammation | Up to day 10 | 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) |
Countries
Ireland
Outcome results
None listed