Hypercoagulability has been demonstrated in COVID-19, leading to respiratory distress and increased mortality. This is an adaptive clinical trial to compare the efficacy and safety of two experimental strategies in patients with COVID-19: ASA or inhaled UFH associated with standard VTE prophylaxis.
Drug: acetylsalicylic acid
acetylsalicylic acid (ASA) 100 mg daily PO up to 14 days OR arterial oxygen saturation greater than or equal to 92% on room air OR PaO2 to FiO2 ratio greater than 200 for 2 consecutive days, whichever is first.
Other Name: aspirin
Drug: Unfractionated heparin nebulized
unfractionated heparin - 25,000 U/ 5 ml nebulized inhalation every 6 hours up to 14 days OR arterial oxygen saturation greater than or equal to 92% on room air OR PaO2 to FiO2 ratio greater than 200 for 2 consecutive days, whichever is first.
Inclusion Criteria:
- Adult ≥18 years of age at time of enrollment
- Subjects with a positive COVID-19 diagnosis by RT-PCR or serologic testing
- Subject (or legally authorized representative) must be willing, understanding and able
to provide written informed consent.
- Only at phase 2:
- onset of symptoms must not exceed 4 weeks
- ICU patients
- PaO2 to FiO2 ratio < 200
Exclusion Criteria:
1. General
- Indications for therapeutic anticoagulation
- History of chronic lung disease oxygen dependent
- Pregnancy
- Death considered imminent and inevitable within 24 hours
- Patients under exclusive palliative care
- Participation in another trial of investigational drug
- Body weight < 40 Kg
- Total bilirubin > 20 mg/dL
- Severe active bleeding
- Persistent GI bleeding
- Known allergy to UFH or LMWH
- History of heparin-induced thrombocytopenia (HIT) within the past 6 months
2. Exclusion criteria at phase 1
- Platelet count < 25,000/mm3
- Bacterial endocarditis
3. Exclusion criteria at phase 2
- Platelet count < 50,000/mm3
- History of surgery in the last 30 days
- Intervention A: allergy to ASA and long-term use of antiplatelet drug
- Intervention B: inhaled nitric oxide use
Vanderson Rocha
Sao Paulo, Brazil
Investigator: Vanderson Rocha, MD.PhD
Contact: +55-11-26617575
vanderson.rocha@hc.fm.usp.br
Investigator:
Vanderson Rocha, Principal Investigator
University of Sao Paulo General Hospital