Key clinical trials of escalated or therapeutic-dose heparin/LMWH vs standard-of-care heparin/LMWH for thromboprophylaxis in hospitalized COVID-19 patients
| Trial . | N . | Population . | Experimental group . | Comparator group . | Primary outcome . | Results (95% CI) . | Pvalue or other . |
|---|---|---|---|---|---|---|---|
| INSPIRATION40 | 562 | ICU | Intermediate-dose heparins | Standard-dose heparins | Major TE + ECMO + ACM | OR 1.06; 0.76-1.48 | P = .70 |
| ACTION41 | 615 | ICU + ward | DOAC IP +30 d | Standard-dose heparins | Time to death + hospitalization/2 | Win ratio 0 · 86; 0 · 59-1 · 22 | P = .40 |
| Multiplatform ICU42 | 1098 | ICU | Therapeutic-dose heparins | Standard + intermediate-dose heparins | Organ support–free days | OR 0.83; 0.67-1.03 | 99% futility |
| Multiplatform ward32,a | 2219 | Ward | Therapeutic-dose heparins | Standard + intermediate-dose heparins | Organ support–free days | OR 1.27; 1.03-1.58 | 98.6% superiority |
| HEP-COVID33 | 257 | ICU + ward DD >4 × ULN | Therapeutic-dose LMWH | Standard + intermediate-dose heparins | Major TE + ACM | RR 0.68, 0.49-0.96 | P = .03b |
| RAPID34 | 465 | Ward Elev DD | Therapeutic-dose heparins | Standard-dose heparins | Death, I(NV)MV, ICU admit | OR 0.59, 0.34-1.02 | P = .06c |
| Trial . | N . | Population . | Experimental group . | Comparator group . | Primary outcome . | Results (95% CI) . | Pvalue or other . |
|---|---|---|---|---|---|---|---|
| INSPIRATION40 | 562 | ICU | Intermediate-dose heparins | Standard-dose heparins | Major TE + ECMO + ACM | OR 1.06; 0.76-1.48 | P = .70 |
| ACTION41 | 615 | ICU + ward | DOAC IP +30 d | Standard-dose heparins | Time to death + hospitalization/2 | Win ratio 0 · 86; 0 · 59-1 · 22 | P = .40 |
| Multiplatform ICU42 | 1098 | ICU | Therapeutic-dose heparins | Standard + intermediate-dose heparins | Organ support–free days | OR 0.83; 0.67-1.03 | 99% futility |
| Multiplatform ward32,a | 2219 | Ward | Therapeutic-dose heparins | Standard + intermediate-dose heparins | Organ support–free days | OR 1.27; 1.03-1.58 | 98.6% superiority |
| HEP-COVID33 | 257 | ICU + ward DD >4 × ULN | Therapeutic-dose LMWH | Standard + intermediate-dose heparins | Major TE + ACM | RR 0.68, 0.49-0.96 | P = .03b |
| RAPID34 | 465 | Ward Elev DD | Therapeutic-dose heparins | Standard-dose heparins | Death, I(NV)MV, ICU admit | OR 0.59, 0.34-1.02 | P = .06c |
Greater treatment effect with elevated DD.
No treatment effect in ICU stratum (RR, 0.92; 95% CI, 0.62-1.39).
Death (secondary outcome) (OR, 0.22; 95% CI, 0.07-0.65; P = .006).
ACM, all-cause mortality; ECMO, extracorporeal membrane oxygenation; I(NV)MV, invasive (noninvasive) mechanical ventilation; OR, odds ratio.