Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study)
Authors: Nagami Yasuaki , Sakai Taishi , Yamamura Masafumi , Nakatani Masami , Katsuno Takayuki , Suekane Takehisa , Uno Hironori , Minamino Hiroaki , Okuyama Masatsugu , Okamoto Junichi , Kumamoto Mitsutaka , Noguchi Atsushi , Yamamori Kazuki , Takaishi Osamu , Ochi Masahiro , Miyazaki Takako , Tsuji Shigetsugu , Ikehara Hisatomo , Kawaguchi Koichiro , Hayashi Tomoyuki , Mannami Tomohiko , Kakimoto Kazuki , Naito Yoshihide , Hashimoto Satoru , Li Zhaoliang , Komeda Yoriaki , Kishino Takaaki , Yamamoto Yoshinobu , Iguchi Mikitaka , Akamatsu Takuji , Horii Toshiki , Miura Ko , Yamashina Takeshi , Sugihara Yuusaku , Watanabe Noboru , Kiyotoki Shu , Fujii Ryoji , Murata Masaki , Ono Satoshi , Narasaka Toshiaki , Kitamura Shinji , Kono Mitsuhiro , Kato Motohiko , Kawaratani Hideto , Tanaka Kyosuke , Yaoita Takao , Yamaguchi Shinjiro , Abe Keiichiro , Kawamura Takuji , Kinoshita Yosuke , Imai Kenichiro , Fujinami Haruka , Yada Tomoyuki , Miyamoto Hayato , Yoshida Hisako , Fujiwara Yasuhiro 
Published: January 2021

Abstract
Background
Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding.

Methods
We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events.

Discussion
The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy.

Trial registration
UMIN-CTR UMIN000023720. Registered on 22 August 2016