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Rivaroxaban for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Design of the PRO-LAPS II STUDY

Published:December 06, 2019DOI:https://doi.org/10.1016/j.ejim.2019.11.015

      Highlights

      • Benefit of extended VTE prophylaxis after laparoscopic cancer surgery undefined.
      • A randomized, double-blind study in laparoscopic surgery for colorectal cancer.
      • To assess the clinical benefit of extended prophylaxis with rivaroxaban.
      • PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery.

      Abstract

      Background

      The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is undefined. Extended prophylaxis with rivaroxaban is effective in reducing post-operative VTE after major orthopedic surgery without safety concern.

      Methods

      PROLAPS II is an investigator-initiated, randomized, double-blind study aimed at assessing the efficacy and safety of extended antithrombotic prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer in patients who had received antithrombotic prophylaxis with low molecular-weight heparin for 7 ± 2 days (NCT03055026). Patients are randomized to receive rivaroxaban (10 mg once daily) or placebo for 3 weeks (up to day 28 ± 2 from surgery).
      The primary study outcome is a composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT or VTE-related death at 28 ± 2 days from laparoscopic surgery. The primary safety outcome is major bleeding defined according to the International Society of Thrombosis and Haemostasis. Symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, major bleeding or death by day 28 ± 2 and by day 90 from surgery are secondary outcomes.
      Assuming an 8% event rate with placebo and 60% reduction in the primary study outcome with rivaroxaban, 323 patients per group are necessary to show a statistically significant difference between the study groups.

      Discussion

      The PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by answering the question on the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

      Keywords

      Abbreviations:

      VTE (venous thromboembolism), LMWH (low-molecular-weight heparin), DVT (ultrasonography-detected), OR (Odds Ratio), Cl (Confidence Interval), RRR (Relative Risk Reduction), LOCF (Last Observation Carried Forward), FAS (Full Analysis Set), PP (Per Protocol), DSMB (Data Safety Monitoring Board)
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