COVID-19
Conditions
Brief summary
Investigator-initiated, multi-centre, randomised, open-label trial of nebulised heparin sodium in addition to standard care compared to standard care alone in hospitalised patients with COVID-19 infection.
Detailed description
Heparin has been used as a medicine for over 75 years. It is used mostly as an anticoagulant (blood thinner), injected under the skin or infused into a vein to prevent or treat large blood clots. Most patients who are eligible for this study are already receiving heparin administered under the skin or into a vein, and this treatment would continue after enrolment in the study, as determined by the treating doctors according to best practice. In this study heparin is administered using a nebuliser. A nebuliser is a device that changes a fluid into a mist of tiny droplets so it can be easily breathed into the lungs. A nebuliser is a commonly used and effective way of giving medications that work in the lungs. Nebulised heparin is not currently a standard treatment, but there are good reasons to think it could help. Lung infections, including COVID-19, cause the widespread formation of tiny blood clots in the small blood vessels and air sacs of the lungs, which make breathing difficult and lead to lung damage. Previous studies of patients with serious breathing problems due to pneumonia and other conditions found that nebulised heparin reduced the formation of small blood clots in the lungs, reduced the amount of injury to the lungs and hastened recovery with faster return to living at home. The virus that causes COVID-19 (the SARS-CoV-2 virus) has 'spikes' on its surface that enable it to attach to cells of the body and enter those cells. Another way that nebulised heparin might help is by sticking to these spikes on the virus and inhibiting the ability of the virus to enter the cells. The main aim is to determine if nebulised heparin reduces the chance that a patient needs help with their breathing from a mechanical ventilator. Other aims are to determine if nebulised heparin increases the chances of surviving and of getting better quicker.
Interventions
DRUGUnfractionated Heparin
Heparin sodium will be administered as a nebulised aerosol dose of 25,000 IU heparin three times a day (TDS) via an Aerogen Solo (Aerogen, Ireland) vibrating mesh aerosol drug nebulizer.
Sponsors
The George Institute
St George Hospital, Australia
St Vincent's Hospital Melbourne
John Hunter Hospital
Royal North Shore Hospital
Australian National University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
investigator-initiated, multi-centre, randomised, open-label trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Currently admitted to hospital * There is a positive sample for COVID-19 within the past 14 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient * Requiring oxygenation according to the modified ordinal clinical scale 4-5
Exclusion criteria
* Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment * Heparin allergy or heparin-induced thrombocytopaenia * Activated partial thromboplastin time (APTT) \> 120 seconds, not due to anticoagulant therapy and does not correct with administration of fresh frozen plasma * Platelet count \< 20 x 10\^9 per L within 48 hours of randomisation * Pulmonary bleeding or uncontrolled bleeding within 48 hours of randomisation * Known or suspected pregnancy * Acute brain injury that may result in long-term disability * Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome * Treatment limitations in place, i.e. not for intubation, not for ICU admission * Death is imminent or inevitable within 24 hours * Clinician objection * Participant consent declined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intubation | 28 days | The primary outcome is intubation (or death, for patients who died before intubation) before or at day 28 after randomisation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 60 days | Survival to hospital discharge censored at day 60 |
| Oxygenation | 28 days | Daily ratio of oxygen saturation by pulse oximetry (SpO2) to the fraction of inspired oxygen (FiO2): (SpO2/FiO2 ratio, highest and lowest levels) |
| Length of hospitalisation | 60 days | Duration of hospital length of stay censored at day 60 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of Intensive Care Unit admission | 60 days | Duration of intensive care unit (ICU) admission censored at day 60 |
| Incidence of bleeding | Day 21 | The rate of bleeding including pulmonary bleeding or other major bleeding assessed daily during intervention censored at 21 days |
| Ventilator free days | 60 days | The number of days without invasive mechanical ventilation censored at day 60 |
Countries
Australia
Outcome results
None listed