Can Nebulised HepArin Reduce acuTE lung injury in Patients with SARS-CoV-2 Requiring Advanced Respiratory support in Ireland

INTERVENTION: Trade Name: Heparin Sodium Product Name: Heparin Sodium Product Code: PL 29831/0111 Pharmaceutical Form: Solution for injection INN or Proposed INN: HEPARIN SODIUM CAS Number: 9041‐08‐1 Other descriptive name: Heparin Concentration unit: IU/ml international unit(s)/millilitre Concentration type: equal Concentration number: 5000‐ CONDITION: Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] This trial will be carried out in invasively ventilated ICU patients with suspected or confirmed COVID‐19 infection PRIMARY OUTCOME: Main Objective: 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.; 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. ; Primary end point(s): Nebulised heparin is administered 6‐hourly from enrolment to day 10 post enrolment, provided the patient is receiving invasive mechanical ventilation. Data collection will be completed at day 60. Secondary Objective: ‐ To determine the impact nebulised heparin on oxygenation index (OI) ; ‐ To determine the effect of nebulised heparin on pulmonary compliance measured on days 1,3,5 and 10.; ‐ Effect of nebulised heparin on other inflammatory and coagulation indices will be assessed to assess for any potential markers of COVID 19 ARDS.; ‐ Time to separation from invasive ventilation to day 28, where non‐survivors to day 28 are treated as though not separated from invasive ventilation. ; ‐ In this study, ‘day 0’ describes the period from randomisation to midnight on the day of enrolment, ‘day 1’ the first calendar day after the day of enrolment, ‘day 2’ the second calendar day after the day of enrolment, and so forth.; ‐ Number tracheotomised 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 intensive care; ‐ Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60; ; Timepoint(s) of evaluation of this end point: Nebulised heparin is administered 6‐hourly from enrolment to day 10 post enrolment, provided the patient is receiving invasive mechanical ventilation. Data collection will be completed at day 60. SECONDARY OUTCOME: Secondary end point(s): N/A Timepoint(s) of evaluation of this end point: Data collection will be completed at day 60. INCLUSION CRITERIA: To be eligible, a patient must satisfy all these INCLUSION CRITERIA: 1. ‐ Confirmed or suspected COVID‐19 If ‘suspected’, results must be pending or testing intended 2. Age 18 years or older 3. Endotracheal tube in place 4. Intubated yesterday or today 5. PaO2 to FIO2 ratio less than or equal to 300 while intubated 6. Acute opacities on chest imaging affecting at least one lung quadrant 7. ‘Acute opacities’ do not include effusions, lobar/lung collapse or nodules 8. Currently in the ICU or scheduled for transfer to the ICU The ‘ICU’ is an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40