Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial

Abstract

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression.

Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events.

Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase).

Conclusion: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.

Trial registration: JRCT Identifier: jRCTs031180124.

Keywords: Anticoagulants; Gynecologic Neoplasms; Gynecologic Surgery; Pulmonary Embolism; Venous Thromboembolism.

Fig. 1. Protocol flowchart. Immediately following the diagnosis of asymptomatic VTE, anticoagulant therapy was initiated. IPC was not used. UFH administration was started within 12 hours postoperatively. Anticoagulant therapy was continued seamlessly for 28 days after surgery, combining UFH, LMWH, and edoxaban.

DOAC, direct oral anticoagulant; IPC, intermittent pneumatic compression; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin; VTE, venous thromboembolism.

Fig. 2. Patient flowchart. Of the 99 patients enrolled, 82 patients were judged to be included in the full analysis set.