A pilot study to test the acceptability and feasibility of registry based randomized control study in Japanese contemporary multi center registries

• Project/Area Number: 20J01755
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: 池村 修寛 東京慈恵会医科大学, 東京慈恵会医科大学 分子疫学研究部, 特別研究員(PD)
• Project Period (FY): 2020-04-24 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Registry based RCT / 2X2ファクトリアルデザイン / 心不全 / ネプリライシン阻害薬 / SGLT2阻害薬 / レジストリを基盤としたランダム化比較試験 / ランダム化比較試験

Outline of Research at the Start

本研究計画では本邦初の試みとして疾患レジストリを基盤としたランダム化比較試験(Regist ry based randomized control trial)を行い、日常臨床行為の有効性を前向きに検討する事を目的とする。具体的には慶應義塾大学循環内科とその関連病院からなる疾患レジストリを基盤とし、実際に行われている診療行為に関して、非盲検化ランダム割り付けを行い実臨床に近い患者群における有用性を検証する予定である。心不全患者に対する利尿薬の使用（長時間vs短時間作用）に関して介入を行い、それが患者予後、および生活の質（quality-of-life）に与える影響に関して検討する予定である。

Outline of Annual Research Achievements

令和2年度より疾患レジストリを基盤としたランダム化比較試験の実践を目的とした研究活動を開始した。その妥当性検証のために、心不全領域で新たに承認された薬剤（ARNI、SGLT2阻害薬）を対象とした2X2ファクトリアルデザインの多施設ランダム化比較試験の研究計画書を作成し、令和3年7月に主研究機関となる慶應義塾大学倫理委員会の承認を得た。UMINに研究計画の登録を行なうと共に（UMIN000045229）、各参加施設での実施許可の申請、ランダム化ソフトウェア、電子的データ入力システム（EDC）の開発を行った。また、臨床研究コーディネーター（CRC）の業務委託など の本研究の実施に向けた準備を進めた。 同年12月には参加施設に向けた説明会を複数回開催した。
令和4年1月から慶應義塾大学病院での患者の登録を、2月より杏林大学病院、埼玉医科大学附属病院、東京慈恵会医科大学附属病院、3月より国立埼玉病院での登録を開始した。なお令和4年4月より、米国で多数のランダム化比較試験を実施しているJohn Spertus教授の研究室での活動を開始し、その方法論やデータ取得に関して直接的な指導を受けた。また同研究室が得意とする循環器内科領域における患者報告アウトカム（PRO）の本研究への応用に関しても定期的な議論を行い、心不全に疾患得意的なPROであるKCCQを本研究のエンドポイントとして扱うこととした。渡米後も研究事務局と定期的に密な連絡をとりながら、順次実施許可申請及び臨床研究コーディネーターの業務委託契約を終えた共同研究機関での患者登録を開始し、令和4年度末時点で合計13施設で患者登録を行い、目標症例数の約８割の登録を終えた（212/240例）。令和5年6月頃に登録患者数が、目標症例数に達する予定であり、そこから半年のフォローアップ期間を経て、年度末には最終的な統計解析まで終える予定である。

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Time Trend in Incidence of Sudden Cardiac Death After Percutaneous Coronary Intervention from 2009 to 2017 (from the Japanese Multicenter Registry) (2023)
  • Author(s): Nakamaru Ryo、Shiraishi Yasuyuki、Niimi Nozomi、Ueda Ikuko、Ikemura Nobuhiro、Suzuki Masahiro、Noma Shigetaka、Inohara Taku、Numasawa Yohei、Fukuda Keiichi、Kohsaka Shun
  • Journal Title: The American Journal of Cardiology Volume: 188 Pages: 44-51
  • DOI: 10.1016/j.amjcard.2022.11.019
  • Peer Reviewed / Open Access
• [Journal Article] Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry (2023)
  • Author(s): Niimi Nozomi、Kohsaka Shun、Shiraishi Yasuyuki、Takei Makoto、Kohno Takashi、Nakano Shintaro、Nagatomo Yuji、Sakamoto Munehisa、Saji Mike、Ikemura Nobuhiro、Inohara Taku、Ueda Ikuko、Fukuda Keiichi、Yoshikawa Tsutomu
  • Journal Title: Clinical Research in Cardiology Volume: - Issue: 8 Pages: 1108-1118
  • DOI: 10.1007/s00392-023-02201-8
  • Peer Reviewed / Open Access
• [Journal Article] Left Ventricular Diastolic Indices and Their Impact on Outcomes in Patients with Recently Diagnosed Atrial Fibrillation (2022)
  • Author(s): Ikemura Nobuhiro、Nakanishi Koki、Spertus John A.、Lam Carolyn S. P.、Kimura Takehiro、Katsumata Yoshinori、Fujisawa Taishi、Ueda Ikuko、Ohki Takahiro、Fukuda Keiichi、Takatsuki Seiji、Kohsaka Shun
  • Journal Title: Journal of Clinical Medicine Volume: 11 Issue: 19 Pages: 5732-5732
  • DOI: 10.3390/jcm11195732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Contrast-Associated Acute Kidney Injury After Percutaneous Coronary Intervention (2022)
  • Author(s): Ikemura Nobuhiro、Inohara Taku、Ueda Ikuko、Fukuda Keiichi、Kohsaka Shun
  • Journal Title: JACC: Cardiovascular Interventions Volume: 15 Issue: 12 Pages: 1283-1283
  • DOI: 10.1016/j.jcin.2022.04.027
  • Peer Reviewed
• [Journal Article] Implications of QRS Prolongation in Patients With Atrial Fibrillation (from a Multicenter Outpatient Registry) (2022)
  • Author(s): Miyama Hiroshi、Ikemura Nobuhiro、Kimura Takehiro、Katsumata Yoshinori、Fujisawa Taishi、Ueda Ikuko、Mitamura Hideo、Negishi Koji、Nagami Keiichi、Fukuda Keiichi、Kohsaka Shun、Takatsuki Seiji
  • Journal Title: The American Journal of Cardiology Volume: 178 Pages: 43-51
  • DOI: 10.1016/j.amjcard.2022.05.011
  • Peer Reviewed
• [Journal Article] Regional variations in the process of care for patients undergoing percutaneous coronary intervention in Japan. (2022)
  • Author(s): Shoji S, Yamaji K, Sandhu AT, Ikemura N, Shiraishi Y, Inohara T, Heidenreich PA, Amano T, Ikari Y, Kohsaka S.
  • Journal Title: Lancet Reg Heal - West Pacific Volume: 22 Pages: 100425-100425
  • DOI: 10.1016/j.lanwpc.2022.100425
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Conventional medical therapy in heart failure patients eligible for the PARADIGM-HF, DAPA-HF, and SHIFT trials (2022)
  • Author(s): Satoshi Shoji, Shun Kohsaka, Yasuyuki Shiraishi, Takashi Kohno, Mitsuaki Sawano, Nobuhiro Ikemura, Nozomi Niimi, Yuji Nagatomo, Toshikazu D Tanaka, Makoto Takei, Tomohiko Ono, Munehisa Sakamoto, Shintaro Nakano, Iwao Nakamura, Soushin Inoue, Keiichi Fukuda, Tsutomu Yoshikawa
  • Journal Title: Int J Cardiol Volume: S0167-5273 Pages: 76-83
  • DOI: 10.1016/j.ijcard.2022.04.020
  • Peer Reviewed / Open Access
• [Journal Article] Catheter ablation improves outcomes and quality of life in Japanese patients with early-stage atrial fibrillation: A retrospective cohort study (2022)
  • Author(s): Seki Yuta、Fujisawa Taishi、Ikemura Nobuhiro、Ibe Susumu、Tsuzuki Ippei、Hashimoto Kenji、Yamashita Terumasa、Miyama Hiroshi、Niimi Nozomi、Suzuki Masahiro、Negishi Koji、Katsumata Yoshinori、Kimura Takehiro、Fukuda Keiichi、Kohsaka Shun、Takatsuki Seiji
  • Journal Title: Heart Rhythm Volume: 19 Issue: 7 Pages: 1076-1083
  • DOI: 10.1016/j.hrthm.2022.02.017
  • Peer Reviewed
• [Journal Article] Characteristics and health‐status outcomes in patients with atrial fibrillation detected via health screening (2022)
  • Author(s): Yamashita Terumasa、Kimura Takehiro、Ikemura Nobuhiro、Niimi Nozomi、Tsuzuki Ippei、Seki Yuta、Ibe Susumu、Hashimoto Kenji、Miyama Hiroshi、Fujisawa Taishi、Katsumata Yoshinori、Tanimoto Kojiro、Nagami Keiichi、Suzuki Masahiro、Kohsaka Shun、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: Clinical Cardiology Volume: 46 Issue: 1 Pages: 32-40
  • DOI: 10.1002/clc.23932
  • Peer Reviewed
• [Journal Article] Rate versus rhythm control in patients with newly diagnosed atrial fibrillation: Effects of the treatment timing on health status outcomes (2022)
  • Author(s): Nakamaru Ryo、Ikemura Nobuhiro、Spertus John A.、Kimura Takehiro、Katsumata Yoshinori、Fujisawa Taishi、Ueno Koji、Inoue Soushin、Ueda Ikuko、Fukuda Keiichi、Takatsuki Seiji、Kohsaka Shun
  • Journal Title: American Heart Journal Volume: 254 Pages: 156-165
  • DOI: 10.1016/j.ahj.2022.09.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Baseline and Postprocedural Health Status Outcomes in Contemporary Patients With Atrial Fibrillation Who Underwent Catheter Ablation: A Report from the Japanese Outpatient Registry (2021)
  • Author(s): Ikemura Nobuhiro、Spertus John A.、Kimura Takehiro、Katsumata Yoshinori、Fujisawa Taishi、Ueda Ikuko、Fukuda Keiichi、Takatsuki Seiji、Kohsaka Shun
  • Journal Title: Journal of the American Heart Association Volume: 10 Issue: 18
  • DOI: 10.1161/jaha.120.019983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Letter by Kuno et al Regarding Article, “Heart Team/Guidelines Discordance Is Associated With Increased Mortality: Data From a National Survey of Revascularization in Patients With Complex Coronary Artery Disease” (2021)
  • Author(s): Kuno Toshiki、Ikemura Nobuhiro、Kohsaka Shun
  • Journal Title: Circulation: Cardiovascular Interventions Volume: 14 Issue: 7
  • DOI: 10.1161/circinterventions.121.010649
  • Peer Reviewed
• [Journal Article] Burden of Mild (<13 g/dl) Anemia in Patients With Atrial Fibrillation (A Report from a Multicenter Registry With Patient-Reported Outcomes) (2021)
  • Author(s): Hashimoto Kenji、Kimura Takehiro、Ikemura Nobuhiro、Katsumata Yoshinori、Fujisawa Taishi、Miyama Hiroshi、Yamashita Terumasa、Nakamura Iwao、Mano Yoshinori、Oki Takahiro、Fukuda Keiichi、Kohsaka Shun、Takatsuki Seiji
  • Journal Title: The American Journal of Cardiology Volume: 157 Pages: 48-55
  • DOI: 10.1016/j.amjcard.2021.06.045
  • Peer Reviewed
• [Journal Article] Phenomapping in patients experiencing worsening renal function during hospitalization for acute heart failure (2021)
  • Author(s): Yagi Ryuichiro、Takei Makoto、Kohsaka Shun、Shiraishi Yasuyuki、Ikemura Nobuhiro、Shoji Satoshi、Niimi Nozomi、Higuchi Satoshi、Goda Ayumi、Kohno Takashi、Nagatomo Yuji、Nishihata Yosuke、Sujino Yasumori、Saji Mike、Ikegami Yukinori、Nakano Shintaro、Takahashi Toshiyuki、Fukuda Keiichi、Yoshikawa Tsutomu
  • Journal Title: ESC Heart Failure Volume: 8 Issue: 6 Pages: 5192-5203
  • DOI: 10.1002/ehf2.13598
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exploring Triaging and Short-Term Outcomes of Early Invasive Strategy in Non-ST Segment Elevation Acute Coronary Syndrome: A Report from Japanese Multicenter Registry (2020)
  • Author(s): Ikemura Nobuhiro、Shiraishi Yasuyuki、Sawano Mitsuaki、Ueda Ikuko、Numasawa Yohei、Noma Shigetaka、Suzuki Masahiro、Momiyama Yukihiko、Hayashida Kentaro、Yuasa Shinsuke、Miyata Hiroaki、Fukuda Keiichi、Kohsaka Shun
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 4 Pages: 1106-1106
  • DOI: 10.3390/jcm9041106
  • Peer Reviewed / Open Access
• [Journal Article] Treatment strategies and subsequent changes in the patient-reported quality-of-life among elderly patients with atrial fibrillation (2020)
  • Author(s): Miura Kotaro、Ikemura Nobuhiro、Kimura Takehiro、Katsumata Yoshinori、Ueda Ikuko、Tanimoto Kojiro、Ohki Takahiro、Shinmura Daisuke、Negishi Koji、Fukuda Keiichi、Takatsuki Seiji、Kohsaka Shun
  • Journal Title: American Heart Journal Volume: 222 Pages: 83-92
  • DOI: 10.1016/j.ahj.2020.01.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Symptom Underrecognition of Atrial Fibrillation Patients in Consideration for Catheter Ablation (2020)
  • Author(s): Katsumata Yoshinori、Kohsaka Shun、Ikemura Nobuhiro、Ueda Ikuko、Hashimoto Kenji、Yamashita Terumasa、Miyama Hiroshi、Fujisawa Taishi、Kimura Takehiro、Tanimoto Kojiro、Momiyama Yukihiko、Suzuki Masahiro、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: JACC: Clinical Electrophysiology Volume: in press Issue: 5 Pages: 565-574
  • DOI: 10.1016/j.jacep.2020.10.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Applicability and Eligibility of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) for Patients who Underwent Revascularization with Percutaneous Coronary Intervention (2020)
  • Author(s): Niimi Nozomi、Sawano Mitsuaki、Ikemura Nobuhiro、Nagai Toshiyuki、Nakano Shintaro、Shoji Satoshi、Shiraishi Yasuyuki、Ueda Ikuko、Numasawa Yohei、Suzuki Masahiro、Noma Shigetaka、Fukuda Keiichi、Kohsaka Shun
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 9 Pages: 2889-2889
  • DOI: 10.3390/jcm9092889
  • Peer Reviewed / Open Access
• [Journal Article] Symptom burden and treatment perception in patients with atrial fibrillation, with and without a family history of atrial fibrillation (2020)
  • Author(s): Fujisawa Taishi、Kimura Takehiro、Kohsaka Shun、Ikemura Nobuhiro、Katsumata Yoshinori、Miyama Hiroshi、Nakajima Kazuaki、Nishiyama Takahiko、Aizawa Yoshiyasu、Kanki Hideaki、Nagami Keiichi、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: Heart and Vessels Volume: 36 Issue: 2 Pages: 267-276
  • DOI: 10.1007/s00380-020-01687-w
  • Peer Reviewed
• [Journal Article] Discrepancy in recognition of symptom burden among patients with atrial fibrillation (2020)
  • Author(s): Katsumata Yoshinori、Kimura Takehiro、Kohsaka Shun、Ikemura Nobuhiro、Ueda Ikuko、Fujisawa Taishi、Nakajima Kazuaki、Nishiyama Takahiko、Aizawa Yoshiyasu、Oki Takahiro、Suzuki Masahiro、Heidenreich Paul A、Fukuda Keiichi、Takatsuki Seiji
  • Journal Title: American Heart Journal Volume: 226 Pages: 240-249
  • DOI: 10.1016/j.ahj.2020.03.024
  • Peer Reviewed
• [Journal Article] Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment (2020)
  • Author(s): Shoji Satoshi、Sawano Mitsuaki、Sandhu Alexander T.、Heidenreich Paul A.、Shiraishi Yasuyuki、Ikemura Nobuhiro、Ueno Koji、Suzuki Masahiro、Numasawa Yohei、Fukuda Keiichi、Kohsaka Shun
  • Journal Title: JAMA Network Open Volume: 3 Issue: 4 Pages: e202004-e202004
  • DOI: 10.1001/jamanetworkopen.2020.2004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] INTERNATIONAL COMPARISONS OF HEALTH STATUS OUTCOMES IN PATIENTS UNDERGOING INITIAL INVASIVE VERSUS CONSERVATIVE MANAGEMENT FOR CHRONIC CORONARY DISEASE: INSIGHTS FROM THE ISCHEMIA TRIAL (2023)
  • Author(s): Nobuhiro Ikemura, John Spertus, et al.
  • Organizer: ACC.23
  • Int'l Joint Research
• [Presentation] IMPACT OF FRAILTY ON CLINICAL OUTCOMES AFTER CORONARY ARTERY BYPASS GRAFTING VERSUS PERCUTANEOUS CORONARY INTERVENTION: INSIGHTS FROM SYNTAX (2023)
  • Author(s): Dan Nguyen, Nobuhiro Ikemura, Khaja Chinnakondepalli, Elizabeth Magnuson, Adam Christopher Salisbury, Patrick W Serruys, David J Cohen, Suzanne Arnold
  • Organizer: ACC.23
  • Int'l Joint Research
• [Presentation] The Importance of Assessment on the Patients' Health Status to Close the Gap to Care Providers (2022)
  • Author(s): 池村 修寛, 香坂 俊, 木村 雄弘, 勝俣 良紀, 植田 育子, 谷本 耕司郎, 鈴木 雅裕, 高月 誠司, 福田 恵一
  • Organizer: 第86回 日本循環器学会 学術集会
• [Presentation] Association Between Baseline Health-Related Quality of Life and Subsequent Clinical Outcomes in Patients with Atrial Fibrillation (2021)
  • Author(s): Nobuhiro Ikemura, John Spertus, et al.
  • Organizer: AHA 2021
  • Int'l Joint Research
• [Presentation] Under-Utilization of Conventional Guideline-Directed Medical Therapy Among Patients Eligible for the Recent Large-Scale Clinical Trials of Heart Failure With Reduced Ejection Fraction (2021)
  • Author(s): Satoshi Shoji, Shun Kohsaka, Yasuyuki Shiraishi, Mitsuaki Sawano, Nobuhiro Ikemura,et al.
  • Organizer: AHA 2021
  • Int'l Joint Research
• [Presentation] Incidence of Sudden Cardiac Death After Percutaneous Coronary Intervention (2021)
  • Author(s): Ryo Nakamaru, Nozomi Niimi, Taku Inohara, Yasuyuki Shiraishi, Nobuhiro Ikemura, et al.
  • Organizer: AHA 2021
  • Int'l Joint Research
• [Presentation] Duration of Disease and the Quality of Life of the Patients with Atrial Fibrillation (2021)
  • Author(s): Ryo Nakamaru, Nobuhiro Ikemura, John Spertus, et al.
  • Organizer: AHA 2021
  • Int'l Joint Research
• [Presentation] Severity of Angina and Incidence of Adverse Cardiovascular Events after Percutaneous Coronary Intervention in Diabetic vs. Non-Diabetic Patients (2021)
  • Author(s): Nozomi Niimi, Satoshi Shoji, Mitsuaki Sawano, Nobuhiro Ikemura, Yasuyuki Shiraishi, Yohei Numasawa, Masahiro Suzuki, Kenichiro Shimoji, Ikuko Ueda, Keiichi Fukuda, Shun Kohsaka
  • Organizer: 第85回日本循環器学会学術集会
• [Presentation] Implication of QRS Prolongation among Patients with Atrial Fibrillation: A Report from Outpatients Registry of Atrial Fibrillation (KiCS-AF) (2021)
  • Author(s): Hiroshi Miyama, Nobuhiro Ikemura, Takehiro Kimura, Yoshinori Katsumata, Taishi Fujisawa, Ikuko Ueda, Hideo Mitamura, Koji Negishi, Keiichi Nagami, Keiichi Fukuda, Shun Kohsaka
  • Organizer: 第85回日本循環器学会学術集会
• [Presentation] Contemporary Use of Vitamin K Antagonist among Newly Referred Patients with Atrial Fibrillation: A Report from Outpatients Registry (2021)
  • Author(s): Ippei Tsuzuki, Nobuhiro Ikemura, Takehiro Kimura, Yoshinori Katsumata, Taishi Fujisawa, Ikuko Ueda, Kojiro Tanimoto, Masahiro Suzuki, Koji Ueno, Keiichi Fukuda, Shun Kohsaka
  • Organizer: 第85回日本循環器学会学術集会