Cecilia Becattini1, Ugo Pace2, Fabio Rondelli3, Paolo Delrio4, Graziano Ceccarelli5, Michela Boncompagni6, Luigina Graziosi7, Adriana Visonà8, Damiano Chiari9, Giampiero Avruscio10, Stefania Frasson11, Gualberto Gussoni12, Alessia Biancafarina13, Giuseppe Camporese14, Annibale Donini15, Andrea Fares Bucci16, Giancarlo Agnelli17. 1. Department of Internal and Cardiovascular Medicine and Stroke Unit, University of Perugia, Italy. Electronic address: Cecilia.becattini@unipg.it. 2. National Cancer Institute, "G. Pascale" Foundation, Napoli, Italy. Electronic address: ugo.pace@yahoo.it. 3. Department of General Surgery, S. Giovanni Battista Hospital, Foligno, Italy. Electronic address: rondellif@hotmail.com. 4. National Cancer Institute, "G. Pascale" Foundation, Napoli, Italy. Electronic address: delrio.paolo@gmail.com. 5. Department of General Surgery, S. Donato Hospital, Arezzo, Italy. Electronic address: g.cecca2003@libero.it. 6. Department of General Surgery, S. Maria della Misericordia Hospital, Perugia, Italy. Electronic address: michela.bcp@gmail.com. 7. Department of Oncology Surgery, University of Perugia, Perugia, Italy. Electronic address: luiginagraziosi@yahoo.it. 8. Department of Vascular Medicine, S.Giacomo Apostolo Hospital, Catelfranco Veneto, Treviso, Italy. Electronic address: adrianavisona@gmail.com. 9. Department of General Surgery, Istituto Clinico Humanitas Mater Domini, Castellanza, Varese, Italy. Electronic address: damiano.chiari@materdomini.it. 10. Department of Cardiac, Thoracic and Vascular Sciences, Unit of Angiology, University Hospital of Padua, Padua, Italy. Electronic address: giampiero.avruscio@gmail.com. 11. Research Department, FADOI Foundation, Milan, Italy. Electronic address: stefania.frasson@fadoi.org. 12. Research Department, FADOI Foundation, Milan, Italy. Electronic address: gualberto.gussoni@gmail.com. 13. Department of General Surgery, S. Donato Hospital, Arezzo, Italy. Electronic address: alessia.biancafarina@gmail.com. 14. Department of Cardiac, Thoracic and Vascular Sciences, Unit of Angiology, University Hospital of Padua, Padua, Italy. Electronic address: giuseppe.camporese@aopd.veneto.it. 15. Department of Oncology Surgery, University of Perugia, Perugia, Italy. Electronic address: annibale.donini@unipg.it. 16. National Cancer Institute, "G. Pascale" Foundation, Napoli, Italy. Electronic address: andrea.faresbucci@gmail.com. 17. Department of Internal and Cardiovascular Medicine and Stroke Unit, University of Perugia, Italy. Electronic address: giancarlo.agnelli@unipg.it.
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.
RCT Entities:
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.