Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial
Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus forma...
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BMJ Publishing Group
2022-07-01
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| author | Keiichi Fukuda Satoshi Yasuda Hiroyuki Tsutsui Toyoaki Murohara Kohtaro Abe Koichiro Tatsumi Junji Kishimoto Yu Taniguchi Yuichi Tamura Koji Todaka Shun Minatsuki Kazuya Hosokawa Yuko Kobayakawa Takumi Inami Nobutaka Ikeda |
| author_facet | Keiichi Fukuda Satoshi Yasuda Hiroyuki Tsutsui Toyoaki Murohara Kohtaro Abe Koichiro Tatsumi Junji Kishimoto Yu Taniguchi Yuichi Tamura Koji Todaka Shun Minatsuki Kazuya Hosokawa Yuko Kobayakawa Takumi Inami Nobutaka Ikeda |
| author_sort | Keiichi Fukuda |
| collection | DOAJ |
| description | Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.Methods and analysis The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.Ethics and dissemination This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.Trial registration number NCT04730037.Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021. |
| format | Article |
| id | doaj-art-6b5f9a98c35d4546ad6c27984161fa58 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-6b5f9a98c35d4546ad6c27984161fa582025-01-31T03:00:10ZengBMJ Publishing GroupBMJ Open2044-60552022-07-0112710.1136/bmjopen-2022-061225Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trialKeiichi Fukuda0Satoshi Yasuda1Hiroyuki Tsutsui2Toyoaki Murohara3Kohtaro Abe4Koichiro Tatsumi5Junji Kishimoto6Yu Taniguchi7Yuichi Tamura8Koji Todaka9Shun Minatsuki10Kazuya Hosokawa11Yuko Kobayakawa12Takumi Inami13Nobutaka Ikeda14Department of Cardiology, Keio University School of Medicine, Tokyo, JapanDepartment of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Cardiovascular Medicine, Faculty of Medical Sciences, Fukuoka, JapanDepartment of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Cardiovascular Medicine, Faculty of Medical Sciences, Fukuoka, JapanDepartment of Respirology, Graduate School of Medicine, Chiba University, Chiba, Chiba, JapanCenter for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan4 Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Cardiology, International University of Health and Welfare Mita Hospital, Tokyo, JapanCenter for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, JapanDepartment of Cardiovascular Medicine, The University of Tokyo, Tokyo, JapanDepartment of Cardiovascular Medicine, Faculty of Medical Sciences, Fukuoka, JapanCenter for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan2 Department of Cardiovascular Medicine, Kyorin University Hospital, Mitaka, JapanDivision of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, JapanIntroduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.Methods and analysis The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.Ethics and dissemination This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.Trial registration number NCT04730037.Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021.https://bmjopen.bmj.com/content/12/7/e061225.full |
| spellingShingle | Keiichi Fukuda Satoshi Yasuda Hiroyuki Tsutsui Toyoaki Murohara Kohtaro Abe Koichiro Tatsumi Junji Kishimoto Yu Taniguchi Yuichi Tamura Koji Todaka Shun Minatsuki Kazuya Hosokawa Yuko Kobayakawa Takumi Inami Nobutaka Ikeda Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial BMJ Open |
| title | Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial |
| title_full | Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial |
| title_fullStr | Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial |
| title_full_unstemmed | Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial |
| title_short | Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial |
| title_sort | efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension protocol for a multicentre randomised warfarin controlled parallel group trial kabuki trial |
| url | https://bmjopen.bmj.com/content/12/7/e061225.full |
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