Phase 3
N=465
Coagulopathy of COVID-19: A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT04362085 ↗Enrolled (actual)
465
Serious AEs
100.0%
Results posted
Jan 2025
Primary outcome: Primary: Composite Outcome of ICU Admission, Non-invasive Positive Pressure Ventilation, Invasive Mechanical Ventilation, or All-cause Death up to 28 Days. — 37; 52 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Therapeutic Anticoagulation (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Unity Health Toronto
- Primary completion
- May 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Composite Outcome of ICU Admission, Non-invasive Positive Pressure Ventilation, Invasive Mechanical Ventilation, or All-cause Death up to 28 Days. |
37; 52 | — |
| SECONDARY All-cause Death |
4; 18 | — |
| SECONDARY Composite Outcome of ICU Admission or All-cause Death |
4; 1 | — |
| SECONDARY Composite Outcome of Mechanical Ventilation or All-cause Death |
23; 28 | — |
| SECONDARY Major Bleeding |
2; 4 | — |
| SECONDARY Red Blood Cell Transfusion |
3; 9 | — |
| SECONDARY Transfusion of Platelets, Frozen Plasma, Prothrombin Complex Concentrate, Cryoprecipiate and/or Fibrinogen Concentrate |
1; 0 | — |
| SECONDARY Renal Replacement Therapy |
2; 5 | — |
| SECONDARY Hospital-free Days Alive up to Day 28 |
19.8; 18.4 | — |
| SECONDARY ICU-free Days Alive up to Day 28 |
26; 24.2 | — |
| SECONDARY Ventilator-free Days Alive up to Day 28 |
26.5; 24.7 | — |
| SECONDARY Organ Support-free Days Alive up to Day 28 |
25.8; 24.1 | — |
| SECONDARY Venous Thromboembolism |
2; 6 | — |
| SECONDARY Arterial Thromboembolism |
0; 1 | — |
| SECONDARY Heparin Induced Thrombocytopenia |
0; 0 | — |
| SECONDARY Changes in D-dimer |
1.9; 2.4 | — |
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.
Eligibility Criteria
The inclusion criteria are:
- 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;
- admitted to hospital for COVID-19;
- 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;
- ≥18 years of age;
- informed consent from the patient (or legally authorized substitute decision maker).
The exclusion criteria are:
- pregnancy;
- hemoglobin 1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation);
- 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);
- 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);
- patient on dual antiplatelet therapy, when one of the agents cannot be stopped safely;
- known bleeding within the last 30 days requiring emergency room presentation or hospitalization;
- known history of a bleeding disorder of an inherited or active acquired bleeding disorder;
- known history of heparin-induced thrombocytopenia;
- known allergy to UFH or LMWH;
- admitted to the intensive care unit at the time of screening;
- 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).
- imminent death according to the judgement of the most responsible physician
- enrollment in another clinical trial of antithrombotic therapy involving pre-intensive care unit hospitalized patients
Data sourced from ClinicalTrials.gov (NCT04362085). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.