Perepu et al.2020 Perepu US, Chambers I, Wahab A, Ten Eyck P, Wu C, Dayal S, et al. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial. J Thromb Haemost. 2021;19(9):2225-2234. https://doi.org/10.1111/jth.15450 https://doi.org/10.1111/jth.15450...
))
|
Open-label RCT |
Adults hospitalized with COVID-19 |
N = 88 Intermediate dose of enoxaparin (of 1 mg/kg/day for a BMI of < 30 kg/m2 or of 0.5 mg/kg 12/12 h for a BMI > 30 kg/m2) |
N = 88 Prophylactic enoxaparin 40 mg/day (for a BMI of < 30 kg/m2) or 30-40 mg 12/12 h (for a BMI > 30 kg/m2) |
Mortality at 30 days Venous/arterial thromboembolism Bleeding |
30 days |
INSPIRATION Investigators et al.2121 INSPIRATION Investigators, Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, et al. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021;325(16):1620-1630. https://doi.org/10.1001/jama.2021.4152 https://doi.org/10.1001/jama.2021.4152...
|
RCT with blinded outcome assessment |
Adult ICU COVID-19 patients within 7 days of hospitalization |
N = 280 Enoxaparin 1 mg/kg/day (120 kg) Changed to unfractionated heparin if kidney function < 30 ml/min |
N = 286 Enoxaparin 40 mg/kg/day |
Venous/arterial thromboembolism Need for ECMO No. of days free of mechanical ventilation ICU discharge Bleeding |
30 days |
REMAP-CAP Investigators et al.1616 REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators, Goligher EC, Bradbury CA, McVerry BJ, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021;385(9):777-789. https://doi.org/10.1056/NEJMoa2103417 https://doi.org/10.1056/NEJMoa2103417...
|
Open-label RCT |
Adult ICU COVID-19 patients requiring respiratory or cardiac support |
N = 534 Anticoagulation with unfractionated or low-molecular-weight heparin |
N = 564 Low-dose thromboprophylaxis or enhanced intermediate-dose thromboprophylaxis |
Venous/arterial thromboembolism No. of organ support-free days Bleeding Survival to hospital discharge |
21 days |
ATTACC Investigators et al.1818 ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators, Lawler PR, Goligher EC, Berger JS, et al. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021;385(9):790-802. https://doi.org/10.1056/NEJMoa2105911 https://doi.org/10.1056/NEJMoa2105911...
|
Open-label RCT |
Adult ward patients with COVID-19 not requiring respiratory or cardiac support |
N = 1,190 Anticoagulation with unfractionated or low-molecular-weight heparin |
N = 1,054 Low-dose thromboprophylaxis or enhanced intermediate-dose thromboprophylaxis |
Venous/arterial thromboembolism No. of organ support-free days Bleeding Survival to hospital discharge |
21 days |
Sholzberg et al.1717 Sholzberg M, Tang GH, Rahhal H, AlHamzah M, Kreuziger LB, Áinle FN, et al. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ. 2021;375:n2400. https://doi.org/10.1136/bmj.n2400 https://doi.org/10.1136/bmj.n2400...
|
Open-label RCT |
Adults hospitalized with COVID-19, a D-dimer above the upper limit of normal, and an SpO2 of < 93% on room air |
N = 228 Anticoagulation with unfractionated or low-molecular-weight heparin |
N = 237 Low-dose thromboprophylaxis with unfractionated or low-molecular-weight heparin |
Mortality Mechanical ventilation or death No. of days free of mechanical ventilation ICU admission or death Venous/arterial thromboembolism No. of organ support-free days Bleeding |
28 days |
Lopes et al.1414 Lopes RD, de Barros E Silva PGM, Furtado RHM, Macedo AVS, Bronhara B, Damiani LP, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397(10291):2253-2263. https://doi.org/10.1016/S0140-6736(21)01203-4 https://doi.org/10.1016/S0140-6736(21)01...
|
Open-label RCT |
Adults hospitalized with COVID-19 within 14 days of the onset of symptoms, a D-dimer above the upper limit of normal, and an SpO2 of < 93% on room air |
N = 310 Rivaroxaban 20 mg/day for stable patients or enoxaparin 1 mg/kg 12/12 h for unstable patients |
N = 304 Low-dose thromboprophylaxis with unfractionated or low-molecular-weight heparin |
Mortality Hospital length of stay Duration of oxygen use Venous/arterial thromboembolism Bleeding |
30 days |
Oliynyk et al.1515 Oliynyk O, Barg W, Slifirczyk A, Oliynyk Y, Dubrov S, Gurianov V, et al. Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy. Life (Basel). 2021;11(10):1032. https://doi.org/10.3390/life11101032 https://doi.org/10.3390/life11101032...
|
Open-label RCT |
Adults hospitalized with COVID-19, a D-dimer > 3 mg/L, and a PaO2 of < 60 mmHg on room air |
N = 84 Anticoagulation with unfractionated or low-molecular-weight heparin |
N = 42 Low-molecular-weight heparin |
Mortality Mechanical ventilation or death |
28 days |
Spyropoulos et al.1919 Spyropoulos AC, Goldin M, Giannis D, Diab W, Wang J, Khanijo S, et al: HEP-COVID Investigators. Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial [published correction appears in JAMA Intern Med. 2022 Feb 1;182(2):239]. JAMA Intern Med. 2021;181(12):1612-1620. https://doi.org/10.1001/jamainternmed.2021.6203 https://doi.org/10.1001/jamainternmed.20...
|
Open-label RCT |
Adults hospitalized with COVID-19 and a D-dimer > 4 times the upper limit of normal, requiring supplemental oxygen |
N = 130 Anticoagulation with enoxaparin 1 mg/kg 12/12 h or 0.5 mg/kg 12/12 h if CrCl = 15-39 mL/min/1.73 m2
|
N = 127 Enoxaparin 30-40 mg/kg once or twice daily or unfractionated heparin 22,500 IU |
Venous/arterial thromboembolism Mortality Bleeding Endotracheal intubation Rehospitalization |
30 days |
Ramacciotti et al.2222 Ramacciotti E, Barile Agati L, Calderaro D, Aguiar VCR, Spyropoulos AC, de Oliveira CCC, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2022;399(10319):50-59. https://doi.org/10.1016/S0140-6736(21)02392-8 https://doi.org/10.1016/S0140-6736(21)02...
|
Open-label RCT |
Discharged COVID-19 patients with an IMPROVE VTE risk score ≥ 4 or = 2-3 and a D-dimer > 1,000 ng/ml during hospitalization |
N = 160 Rivaroxaban 10 mg/day for 35 days |
N = 160 Standard of care |
Mortality related to venous/arterial thromboembolism Bleeding |
30 days |