Living meta-analysis and evidence synthesis of therapies for COVID-19

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COALIZAO ACTION, 2021 NCT04394377

anticoagulant, curative dose (n=311) vs. anticoagulant, prophylactic dose (n=304)

randomized controlled trial   some concerns about risk of bias

Studied treatment

therapeutic anticoagulation
in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3–0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30.

Control treatment

prophylactic anticoagulation
standard in-hospital enoxaparin or unfractionated heparin

Patients

COVID 19 hospitalized

Method

open-label

31 hospitals in Brazil

Remark

ATTACC, ACTIV-4a, and REMAP-CAP (noncritically ill patients), 2021 NCT02735707

anticoagulant, curative dose (n=1190) vs. anticoagulant, prophylactic dose (n=1054)

randomized controlled trial   some concerns about risk of bias

Studied treatment

therapeutic-dose anticoagulation with heparin

Control treatment

usual care pharmacological thromboprophylaxis

Patients

COVID-19 mild to moderate

Method

open-label

prematurely discontinued after a planned adaptive analysis of data from 1398 patients showed that the prespecified stopping criteria for superiority of therapeutic-dose anticoagulation had been reached in both the high and low d-dimer cohorts

Remark

COVID-PACT, 2022

anticoagulant, curative dose (n=191) vs. anticoagulant, prophylactic dose (n=191)

randomized controlled trial   some concerns about risk of bias

Studied treatment

full-dose anticoagulation

Control treatment

standard-dose prophylactic anticoagulation

Patients

COVID-19 severe or critically

Method

open label

34 centers, United States

2x2 factorial deisgn with clopidogrel or no antiplatelet therapy; recruitment was stopped early in 03/2022 (∼50% planned recruitment) due to waning ICU-level COVID-19 rates

Remark

REMAP-CAP, ACTIV-4a, ATTACC (critically ill patients), 2021 NCT02735707

anticoagulant, curative dose (n=591) vs. anticoagulant, prophylactic dose (n=616)

randomized controlled trial   some concerns about risk of bias

Studied treatment

therapeutic anticoagulation with heparin
Therapeutic anticoagulation was administered according to local site protocols for the treatment of acute venous thromboembolism for up to 14 days or recovery

Control treatment

pharmacological thromboprophylaxis as per local usual care

Patients

COVID-19 severe or critically

Method

open-blind

Remark

NCT02735707, NCT04505774, NCT04359277, NCT04372589