Hemostasis in COVID-19: an Adaptive Clinical Trial

Study Overview
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Brief Summary
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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.

Official Title
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Dynamics of Hemostatic Parameters in COVID-19 and Comparison of Intervention Strategies Through Adaptive Clinical Trial

Conditions
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COVID-19

Intervention / Treatment
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* Drug: acetylsalicylic acid
* Drug: Unfractionated heparin nebulized


Participation Criteria
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Eligibility Criteria
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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: 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 Exclusion criteria at phase 1 Platelet count < 25,000/mm3 Bacterial endocarditis 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: phase 1<br>Observational arm | |
| Experimental: phase 2A<br>Acetylsalicylic acid | Drug: acetylsalicylic acid<br>* 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.<br>* Other names: aspirin;|
| Experimental: phase 2B<br>inhaled unfractionated heparin | Drug: Unfractionated heparin nebulized<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo arm for Phase 2A | Drug: acetylsalicylic acid<br>* 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.<br>* Other names: aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital discharge - alive / death | Number of COVID-19 positive patients who are alive within 30 days of symptoms onset | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of mechanical ventilation free days | Comparison of length of mechanical ventilation free days between each treatment arm | 30 days | 
| Length of renal replacement therapy free days | Comparison of length of renal replacement therapy free days between each treatment arm | 30 days | 
| Number of documented venous thromboembolism or arterial thrombosis | Comparison of number of thrombosis events between each treatment arm. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulation, SARS-CoV-2, Thrombosis, Coagulopathy, Respiratory failure