Table 1.
Study characteristics of the eight included trials.
| Study Reference | Study Design | Setting and Patient Status | Randomised Patients | Intervention | Comparator | Selected Outcomes |
|---|---|---|---|---|---|---|
| INSPIRATION, [22,28] | RCT, open-label, multi-centre | ICU WHO 5–9, with 45% WHO 5 |
600 | Intermediate-dose anticoagulation A
with enoxaparin 1 mg/kg OD sc for 30 days; weight and CrCI adjusted |
Standard thromboprophylaxis with enoxaparin 40 mg OD; weight and CrCI adjusted |
30-day mortality, 90-day mortality, any venous thrombotic events, any venous thrombotic events or death, major bleeding |
| Perepu-2021 [27] | RCT, multi-centre, open-label | Hospitalised + mod. ISTH Overt DIC score ≥3 + ICU, WHO 5–9, no details on respiratory status reported | 173 | Intermediate-dose anticoagulation A
with enoxaparin 1 mg/kg sc OD until hospital discharge; weight and CrCI adjusted |
Standard thromboprophylaxis with enoxaparin 40 mg sc OD until hospital discharge or extended beyond, weight and CrCI adjusted |
30-day mortality, any venous thrombotic events, major bleeding |
| HESACOVID, [25] | RCT, open-label, single centre | ICU WHO ≥ 7 |
20 | Therapeutic-dose anticoagulation A
with enoxaparin 1 mg/kg sc BID for at least 96 h and up to 14 days |
Standard thromboprophylaxis with enoxaparin 40 mg OD; weight and CrCI adjusted |
28-day mortality, in-hospital mortality, any thrombotic event |
| ACTION [26] |
RCT, multi-centre, open-label | Hospitalised/ ICU + ↑ D-Dimer, WHO 4–9, with 85% WHO 4–5 |
614 | Therapeutic-dose anticoagulation A
with rivaroxaban 20 mg po OD (280 patients, 90%) for 30 days |
Standard thromboprophylaxis with enoxaparin 40 mg sc OD, continued until or extended beyond hospital discharge; weight and CrCI adjusted |
30-day mortality, survival until hospital discharge (30 days), any thrombotic event, any thrombotic event or death, major bleeding |
| RAPID 2021 [29] |
RCT, multi-centre, open-label | Hospitalised + ↑ D-Dimer, WHO 4–5, with 6% WHO 6 |
465 | Therapeutic-dose anticoagulation A
Enoxaparin 1 mg/kg sc BID; weight and CrCI adjusted |
Standard thromboprophylaxis with enoxaparin 40 mg OD, weight and CrCl adjusted |
All-cause mortality, venous thrombotic events, major bleeding |
| ATTACC, ACTIV-4a, REMAP-CAP Non-critically ill [24] |
RCT, open-label, Bayesian, adaptive, multiplatform | Hospitalised WHO 4–5, with 5% WHO 6–7 |
2244 | Therapeutic-dose anticoagulation A
(79.6%) with enoxaparin 1 mg/kg sc minus 10% BID, weight and CrCl adjusted |
Standard low- or intermediate-dose thromboprophylaxis with 78.7 %: enoxaparin, 9.6%: dalteparin; Low-dose: 71.7%, intermediate-dose: 26.5% subtherapeutic-dose: 0.8% therapeutic-dose: 0.9% |
In-hospital mortality, clinical worsening: intubation or death, clinical improvement: discharged without receiving organ support, any thrombotic event, any thrombotic event or death, major bleeding |
| ATTAC, ACTIV-4a, REMAP-CAP Critically ill [23] |
RCT, open-label, Bayesian, adaptive, multiplatform | ICU WHO 6–9, 1.5% WHO 4–5 |
1207 | Therapeutic-dose anticoagulation A
(77.6%) with enoxaparin 1 mg/kg minus 10% BID, weight and CrCl adjusted |
Standard low- or intermediate-dose thromboprophylaxis with 52.1%: enoxaparin, 32.8%: dalteparin; Low-dose: 40.4%, Intermediate-dose: 51.7% Subtherapeutic-dose: 1.8% Therapeutic-dose: 6.1% |
In-hospital mortality, any thrombotic event, any thrombotic event or death, major bleeding |
| HEP-COVID 2021 [30] |
RCT, multi-center, open-label | Hospitalised + ↑ D-Dimer or ISTH SIC score ≥ 4, WHO 5–7, with 77% WHO 5, both strata reported for some outcomes |
257 | Therapeutic-dose anticoagulation A with enoxaparin 1 mg/kg sc BID, or 40 mg sc OD/BID weight and CrCI adjusted, until hospital discharge | Standard thromboprophylaxis with enoxaparin 40 mg sc OD/BID weight and CrCI adjusted, until hospital discharge |
All-cause mortality, any thromboembolic event, any thromboembolic event or death, major bleeding |
RCT, randomised controlled trial; ICU, intensive care unit; sc, sub-cutaneous; OD, once daily; BID, twice daily; UFH, unfractionated heparin; CrCl, creatinine clearance; +, plus; ↑, elevated. A Defined according to trial protocol.