COVID-PACT (anticoagulant therapy)
Trial question
Is full-dose anticoagulation prophylaxis superior to standard-dose prophylactic anticoagulation in critically ill patients with COVID-19?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 382
382 patients (156 female, 226 male).
Inclusion criteria: adult patients with COVID-19 infection requiring ICU-level of care.
Key exclusion criteria: use of full-dose anticoagulation; contraindication to antithrombotic therapy; high risk of bleeding; heparin-induced thrombocytopenia; or ischemic stroke within the past 2 weeks.
Interventions
N=191 full-dose anticoagulation (intravenous UFH or subcutaneous LMWH).
N=191 prophylactic-dose anticoagulation (LMWH).
Primary outcome
Rate of death due to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, MI, acute ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days, an unmatched win ratio
12.3%
6.4%
12.3 %
9.2 %
6.2 %
3.1 %
0.0 %
Full-dose
anticoagulation
Prophylactic-dose
anticoagulation
Significant
increase ▲
NNH = 16
Significant increase in the rate of death due to venous or arterial thrombosis, PE, clinically evident DVT, MI, AIS, systemic embolic event or acute limb ischemia, or clinically silent DVT, through hospital discharge or 28 days, an unmatched win ratio (12.3% vs. 6.4%).
Secondary outcomes
Significant decrease in the rate of death due to venous or arterial thrombosis, PE, clinically evident DVT, MI, AIS, systemic embolic event or acute limb ischemia, or clinically silent DVT, through hospital discharge or 28 days, time-to-first event analysis (9.9% vs. 15.2%; HR 0.56, 95% CI 0.32 to 0.99).
No significant difference in death attributable to venous or arterial thrombosis, PE, clinically evident DVT, MI, AIS, systemic embolic event or acute limb ischemia (7.3% vs. 12%; HR 0.55, 95% CI 0.28 to 1.08).
No significant difference in all-cause mortality (18.8% vs. 16.8%; HR 1.1, 95% CI 0.68 to 1.79).
Safety outcomes
No significant difference in fatal and life-threatening bleeding.
Significant difference in GUSTO moderate and severe bleeding (7.9% vs. 0.5%).
Conclusion
In adult patients with COVID-19 infection requiring ICU-level of care, full-dose anticoagulation was superior to prophylactic-dose anticoagulation with respect to the rate of death due to venous or arterial thrombosis, PE, clinically evident DVT, MI, AIS, systemic embolic event or acute limb ischemia, or clinically silent DVT, through hospital discharge or 28 days, an unmatched win ratio.
Reference
Erin A Bohula, David D Berg, Mathew S Lopes et al. Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients with COVID-19: COVID-PACT. Circulation. 2022 Nov;146(18):1344-1356.
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