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Table 1 Characteristics of the 11 RCTs

From: Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis

Author-year

Design

Study population

Intervention

Total, n

Age, median (IQR), year

Male, %

BMI, median (IQR), kg/m2

Spyropoulos-2021 [21]

multicenter, active control randomized clinical trial

Hospitalized with COVID-19 (noncritically and critically ill)

Therapeutic (TA): enoxaparin (1 mg/kg BID or 0.5 mg/kg BID)

129

65.8 ± 13.9a

52.7

31.2 ± 9.3a

Standard (PA): LMWH (Up to 22,500 IU BID or TID) or enoxaparin (30 mg or 40 mg QD or BID).et

124

67.7 ± 14.1a

54.8

29.8 ± 13.6a

Lemos-2020 [13]

open-label RCT single-center, phase II

Hospitalized with COVID-19 (and ARDS)

Therapeutic (TA): enoxaparin (1 mg/kg BID or 0.75 mg/kg BID or 1 mg/kg QD)

10

55 ± 10a

90

33 ± 8a

Prophylactic (PA): enoxaparin (40 mg QD or 40 mg BID) or UFH (5000 IU TID or 7500 IU TID)

10

58 ± 16a

70

34 ± 8a

Goligher-2021 [12]

open-label RCT adaptive, multiplatform

Hospitalized with severe COVID-19(critically ill)

Therapeutic (TA): UFH or LMWH

536

60.4 ± 13.1a

72.2

30.4 (26.9–36.1)

Usual-Care (PA): local standard venous thromboprophylaxis

567

61.7 ± 12.5a

67.9

30.2 (26.4–34.9)

Lawler-2021 [22]

open-label RCT adaptive, multiplatform

Hospitalized with COVID-19(noncritically ill)

Therapeutic (TA): UFH or LMWH

1181

59.0 ± 14.1a

60.4

29.8 (26.3–34.7)

Usual-Care (PA): local standard venous thromboprophylaxis

1050

58.8 ± 13.9a

56.9

30.3 (26.7–34.9)

Connors-2021 [26]

adaptive, randomized, double-blind, placebo-controlled trial

Hospitalized with COVID-19 (symptomatic but clinically stable outpatients)

Therapeutic (TA): apixaban (5 mg BID)

164

52 (47–58)

37.8

31.1 (26.2–35.4)

Prophylactic (PA): apixaban (2.5 mg BID)

165

55 (46–61)

42.4

29.9 (26.2–34.8)

Marcos-Jubilar-2021 [23]

open-label, multicenter RCT

Hospitalized with COVID-19 (noncritically ill)

Therapeutic (TA): bemiparin (115 IU/kg QD)

32

62.3 ± 12.2a

53.1

25.8 (24.0–29.4)

Standard (PA): bemiparin (3500 IU QD)

33

63.0 ± 13.7a

72.7

26.1 (24.1–28.8)

Sholzberg-2021 [24]

Randomized controlled, adaptive, open label clinical trial.

Hospitalized with COVID-19(and elevated d-dimer)

Therapeutic (TA): UFH or LMWH

228

60.4 ± 14.1a

53.9

30.3 ± 6.4a

Prophylactic (PA): UFH or LMWH

237

59.6 ± 15.5a

59.5

30.2 ± 7.0a

Morici-2021 [25]

open-label, multicenter, controlled, randomized trial

Hospitalized with COVID-19 (noncritically ill)

Therapeutic (TA): enoxaparin (40 mg BID)

91

60 (53–73)

61.5

26 (24–28)

Prophylactic (PA): enoxaparin (40 mg QD)

92

59 (48–72)

64.1

25 (23–28)

Sadeghipour-2021 [27]

Multicenter randomized trial

Admitted to ICU with COVID-19

Intermediate (TA): enoxaparin (1 mg/kg QD)

276

62(51–70.7)

58.7

26.7 (24.4–29.1)

Standard (PA): enoxaparin (40 mg QD)

286

61(47–71)

57

27.2 (24.3–29.1)

Lopes-2021 [14]

open-label RCT pragmatic

Hospitalized with COVID-19 (stable and unstable)

Therapeutic (TA): rivaroxaban (20 mg or 15 mg QD)

311

56.7 ± 14.1a

62

30.3 ± 6.0a

Prophylactic (PA): standard in-hospital enoxaparin or UFH

304

56.5 ± 14.5a

58

30.3 ± 6.1a

Perepu-2021 [11]

open-label RCT multi-center

Hospitalized with COVID-19 (ICU and/or coagulopathy)

Intermediate (TA): enoxaparin (40 mg QD or 30 mg BID or 40 mg BID)

87

65 (24–86)

54

30.0 (24.7–36.6)

Standard (PA): enoxaparin (1 mg/kg QD) or0.5 mg/kg BID

86

63.5 (30–85)

58

30.7 (27.2–35.8)

  1. Abbreviations: BMI Body mass index, IQR Interquartile range, COVID-19 Coronavirus disease 2019, TA Therapeutic anticoagulation, PA Prophylactic anticoagulation, LMWH Low molecular weight heparin, UFH Unfractionated heparin, ARDS Advanced remote display system, QD Once daily, BID Twice daily, TID Thrice daily
  2. aReported as mean ± standard deviation