Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty

doi:10.1001/jama.2019.20687

Pulmonary vascular disease & thromboembolismRandomised controlled trial

Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty

JAMAPublished 14 Jan 2020

Randomised controlled trial
phase 2
noninferiority
open-label
adjudicator-blinded
observer blinding for osocimab doses
54 hospitals in 13 countries

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Authors' conclusion

Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively.

Study context

Population: Adults undergoing unilateral knee arthroplasty600 per-protocol analysed
Participants: 813 adults

Comparison: Osocimab vs enoxaparin and apixaban for thromboprophylaxis
Postoperative 0.3 mg/kgn = 107
Postoperative 0.6 mg/kgn = 65
Postoperative 1.2 mg/kgn = 108
Postoperative 1.8 mg/kgn = 106
Preoperative 0.3 mg/kgn = 109
Preoperative 1.8 mg/kgn = 108
Enoxaparinn = 105reference
Apixabann = 105
Primary endpoint: VTE incidence (mandatory bilateral venography or confirmed symptomatic DVT or PE)
Follow-up: 10 to 13 days postoperatively

Primary result

As reported in the abstract

Osocimab 0.3 mg/kg postop23.7%18 events

Osocimab 0.6 mg/kg postop15.7%8 events

Osocimab 1.2 mg/kg postop16.5%13 events

Osocimab 1.8 mg/kg postop17.9%14 events

Osocimab 0.3 mg/kg preop29.9%23 events

Osocimab 1.8 mg/kg preop11.3%9 events

Enoxaparin26.3%20 of 105

Apixaban14.5%12 of 105

Each group vs enoxaparinRisk difference (2-sided 90% CI)

Osocimab 1.8 mg/kg preopsuperiority met

15.1%(4.9%–25.2%)

Non-inferiority margin 5 as printed, not drawn

Risk difference

Osocimab 0.6 mg/kg postop · noninferiority met: 10.6% (1-sided 95% CI −1.2% to ∞)
Osocimab 1.2 mg/kg postop · noninferiority met: 9.9% (1-sided 95% CI −0.9% to ∞)
Osocimab 1.8 mg/kg postop · noninferiority met: 8.4% (1-sided 95% CI −2.6 to ∞)
Osocimab 0.3 mg/kg postop · noninferiority not met: 2.6% (1-sided 95% CI −8.9% to ∞)
Osocimab 0.3 mg/kg preop · noninferiority not met: −3.6% (1-sided 95% CI −15.5% to ∞)

Safety

Major or clinically relevant nonmajor bleeding · until 10 to 13 days postoperatively

Enoxaparin5.9%

Apixaban2%

Major or clinically relevant nonmajor bleeding — Osocimab (any dose): up to: 4.7%

Reference

Journal: JAMA
Published: 14 Jan 2020
DOI: 10.1001/jama.2019.20687
PubMed: 31935028
Registration: NCT03276143

Study type: Randomised controlled trial
Topic: Pulmonary vascular disease & thromboembolism

Comparison

Osocimab (various doses) vs enoxaparin and apixaban for thromboprophylaxis

Intervention details

Postoperative 0.3 mg/kg: single IV osocimab postoperative dose 0.3 mg/kg
Postoperative 0.6 mg/kg: single IV osocimab postoperative dose 0.6 mg/kg
Postoperative 1.2 mg/kg: single IV osocimab postoperative dose 1.2 mg/kg
Postoperative 1.8 mg/kg: single IV osocimab postoperative dose 1.8 mg/kg
Preoperative 0.3 mg/kg: single IV osocimab preoperative dose 0.3 mg/kg
Preoperative 1.8 mg/kg: single IV osocimab preoperative dose 1.8 mg/kg
Enoxaparin: 40 mg subcutaneous enoxaparin once daily
Apixaban: 2.5 mg oral apixaban twice daily

Key notes

per-protocol population
noninferiority margin 5% vs enoxaparin

Original publication

Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty. JAMA. Published 14 January 2020. doi:10.1001/jama.2019.20687

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Summarised from the published abstract; every number is checked against it