Rivaroxaban versus placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer

The clinical benefit of extended prophylaxis for venous thromboembolism after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROLAPS-II was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10mg once daily) or placebo to be started at 7±2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed venous thromboembolism, asymptomatic ultrasonography-detected deep vein thrombosis or venous thromboembolism-related death at 28±2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with three of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval, 0.07 to 0.94; log-rank P=0.032). Major bleeding occurred in none of the patients in the placebo group and in two patients in the rivaroxaban group (0.7%, 95% confidence interval 0 to 1.0). Oral rivaroxaban was more effective than placebo for extended prevention of venous thromboembolism after laparoscopic surgery for colorectal cancer without an increase in major bleeding. Trial registration: ClinicalTrials.gov. number NCT03055026.