A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care as a Rapid Response to (SARS-CoV-2) COVID-19 Pandemic

• Status: Completed
• Trial end date: 2021-10-14
• Target enrollment: 0
• Participant gender: All

Summary

Coagulopathy of COVID-19 afflicts approximately 20% of patients with severe COVID-19 and is associated with need for critical care and death. COVID-19 coagulopathy is characterized by elevated D-dimer, an indicator of fibrin formation and clot lysis, and a mildly prolonged prothrombin time, suggestive of coagulation consumption. To date, it seems that COVID-19 coagulopathy manifests with thromboembolism, thus anticoagulation may be of benefit. We propose to conduct a parallel pragmatic multi-centre open-label randomized controlled trial to determine the effect of therapeutic anticoagulation compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sao Paulo General Hospital
• Collaborators: St. Michael's Hospital, Toronto; Unity Health Toronto; University of Vermont Medical Center

Criteria

The inclusion criteria are:

1. laboratory confirmed diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification.Positive test prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission;

2. admitted to hospital for COVID-19;

3. one D-dimer value above ULN (5 days (i.e. 120 hours) of hospital admission) and either: a) D-Dimer ≥2 times ULN; or b) D-dimer above ULN and oxygen saturation ≤ 93% on room air;

4. ≥18 years of age;

5. informed consent from the patient (or legally authorized substitute decision maker).

The exclusion criteria are:

1. pregnancy;

2. hemoglobin <80 g/L in the last 72 hours;

3. platelet count <50 x 10^9/L in the last 72 hours;

4. known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation);

5. known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation);

6. patient already on intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration);

7. patient already on therapeutic anticoagulation at the time of screening (low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban);

8. patient on dual antiplatelet therapy, when one of the agents cannot be stopped safely;

9. known bleeding within the last 30 days requiring emergency room presentation or hospitalization;

10. known history of a bleeding disorder of an inherited or active acquired bleeding disorder;

11. known history of heparin-induced thrombocytopenia;

12. known allergy to UFH or LMWH;

13. admitted to the intensive care unit at the time of screening;

14. treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening (of note: high flow oxygen delivery via nasal cannula is acceptable and is not an exclusion criterion).

15. imminent death according to the judgement of the most responsible physician

16. enrollment in another clinical trial of antithrombotic therapy involving pre-intensive care unit hospitalized patients