None listed
Conditions
Brief summary
The search for an effective treatment for COVID-19 is underway around the world. A trial of nebulised heparin is warranted. A recent (not yet published; still under journal review) pre-pandemic double-blind multi-centre randomised study of 256 mechanically ventilated patients with or at risk of developing the Acute Respiratory Distress Syndrome (ARDS) of which 47% had ARDS, led by our group, found important pre-specified secondary outcomes were significantly improved with nebulised heparin. There was no evidence of harm. COVID-19 is associated with the development of ARDS displaying the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. The anticoagulant actions of nebulised heparin limit fibrin deposition. Serendipitously, unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents its entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. For these reasons we believe a trial of nebulised heparin in patients with COVID-19 is warranted. Our hypothesis is that nebulised heparin will reduce the time to separation from invasive ventilation at Day 28. Nebulised heparin sodium 25,000 Units, will be administered 6-hourly with a vibrating mesh nebuliser while patients are receiving invasive mechanical ventilation up to Day 10. The dose and methodology of nebulisation were established in previous clinical trials by our group. The intervention is given in addition to standard care.
Interventions
Nebulised (Vibrating mesh nebuliser) heparin sodium 25,000 IU in 5 ml 6-hourly to day 10 while invasively ventilated in addition to standard care.
The medication will be prescribed and administration documented in the medical record.
Sponsors
St Vincents Hospital Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age 18 years or older In ICU or scheduled for transfer to ICU Endotracheal tube in place Intubated yesterday or today PaO2 to FIO2 ratio less than or equal to 300 while intubated Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least one lung quadrant on chest X-ray or CT The acute opacities on chest X-ray or CT are most likely due to COVID-19 There is a PCR positive sample for SARS-CoV-2 within the past 21 days or there are results pending or further testing is planned
Exclusion criteria
Enrolled in another clinical trial that is unapproved for co-enrolment Heparin allergy or heparin-induced thrombocytopaenia APTT > 120 seconds and this is not due to anticoagulant therapy Platelet count < 20 x 10^9 per L Pulmonary bleeding Uncontrolled bleeding Pregnant or might be pregnant Receiving or about to commence ECMO or HFOV Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome Acute brain injury that may result in long-term disability Usually receives home oxygen Dependent on others for personal care due to physical or cognitive decline Death is imminent or inevitable within 24 hours The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification Clinician objection
Outcome results
None listed