ACTIV-4A
Trial question
What is the effect of P2Y12 inhibitor plus heparin in non-critically ill patients hospitalized for COVID-19?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 562
562 patients (233 female, 329 male).
Inclusion criteria: non-critically ill patients hospitalized for COVID-19.
Key exclusion criteria: severe illness requiring admission to ICU; imminent death; pregnancy; contraindication to anticoagulation; hemoglobin < 8 g/dL; platelet count < 50x 10⁹/L.
Interventions
N=293 P2Y12 inhibitor plus heparin (ticagrelor, clopidogrel, or prasugrel plus therapeutic dose heparin for 14 days or until hospital discharge).
N=269 usual care (therapeutic dose of heparin only).
Primary outcome
Organ support-free days
21 days
21 days
21.0 days
15.8 days
10.5 days
5.3 days
0.0 days
P2Y12 inhibitor plus
heparin
Usual
care
No significant
difference ↔
No significant difference in organ support-free days (21 days vs. 21 days; aOR 0.83, 95% CI 0.55 to 1.25).
Secondary outcomes
No significant difference in major thrombotic events or death in the hospital (6.1% vs. 4.5%; aOR 1.42, 95% CI 0.64 to 3.13).
No significant difference in thrombotic events or death in the hospital (6.8% vs. 4.5%; aOR 1.6, 95% CI 0.73 to 3.5).
No significant difference in major bleeding events or death in the hospital (6.1% vs. 3.7%; aOR 1.8, 95% CI 0.79 to 4.1).
Safety outcomes
No significant difference in major bleeding events.
Conclusion
In non-critically ill patients hospitalized for COVID-19, P2Y12 inhibitor plus heparin was not superior to usual care with respect to organ support-free days.
Reference
Jeffrey S Berger, Lucy Z Kornblith, Michelle N Gong et al. Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2022 Jan 18;327(3):227-236.
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