{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:40:12Z","timestamp":1762522812849,"version":"3.37.3"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ck0106672h0001"],"award-info":[{"award-number":["21ck0106672h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns. However, clinical trials from the USA have reported conflicting results. A Japanese phase II study investigated the efficacy and safety of ramelteon for delirium prevention following gastrectomy in patients aged \u226575\u00a0years, with findings suggesting the feasibility of a phase III trial. The aim of this multi-centre, double-blind, randomized placebo-controlled phase III trial is to evaluate the effectiveness and safety of oral ramelteon for postoperative delirium prevention in cancer patients aged \u226565\u00a0years as advanced medical care. The trial protocol is described here.<\/jats:p>","DOI":"10.1093\/jjco\/hyad061","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T06:43:27Z","timestamp":1687329807000},"page":"851-857","source":"Crossref","is-referenced-by-count":2,"title":["A multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of ramelteon for the prevention of postoperative delirium in elderly cancer patients: a study protocol for JORTC-PON2\/J-SUPPORT2103\/NCCH2103"],"prefix":"10.1093","volume":"53","author":[{"given":"Ryoichi","family":"Sadahiro","sequence":"first","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Hatta","sequence":"additional","affiliation":[{"name":"Juntendo University Nerima Hospital Department of Psychiatry, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Tohoku University Graduate School of Medicine Division of Biostatistics, , Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enokido","family":"Masanori","sequence":"additional","affiliation":[{"name":"National Cancer Center East, National Cancer Center Japan Department of Psycho-Oncology, , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-9377","authenticated-orcid":false,"given":"Yoshinobu","family":"Matsuda","sequence":"additional","affiliation":[{"name":"National Hospital Organization Kinki-Chuo Chest Medical Center Department of Psychosomatic Internal Medicine, , Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asao","family":"Ogawa","sequence":"additional","affiliation":[{"name":"National Cancer Center East, National Cancer Center Japan Department of Psycho-Oncology, , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusei","family":"Iwata","sequence":"additional","affiliation":[{"name":"National Cancer Center East, National Cancer Center Japan Department of Psycho-Oncology, , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Tokoro","sequence":"additional","affiliation":[{"name":"National Hospital Organization Kinki-Chuo Chest Medical Center Department of Psychosomatic Internal Medicine, , Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Nakahara","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1764-1763","authenticated-orcid":false,"given":"Takatoshi","family":"Hirayama","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Yanai","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Kayano","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Ariyoshi","sequence":"additional","affiliation":[{"name":"NPO JORTC Data Centre, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Oyamada","sequence":"additional","affiliation":[{"name":"NPO JORTC Data Centre, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Uchitomi","sequence":"additional","affiliation":[{"name":"Institute for Cancer Control, National Cancer Center Japan Division of Survivorship Research, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Akechi","sequence":"additional","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences Department of Psychiatry and Cognitive-Behavioral Medicine, , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-2851","authenticated-orcid":false,"given":"Noboru","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Department of Experimental Therapeutics, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Okita","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Clinical Trial Support Office, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiko","family":"Yorikane","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Clinical Trial Support Office, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuaki","family":"Shimada","sequence":"additional","affiliation":[{"name":"National Cancer Center Japan National Cancer Center Hospital, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Furukawa","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Pharmacy, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Pharmacy, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Maeda","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Pharmacy, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsufumi","family":"Sato","sequence":"additional","affiliation":[{"name":"National Cancer Center Japan Department of Anesthesia and Intensive Care, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asuko","family":"Sekimoto","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Nursing, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiyuki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Nursing, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Bureau of International Health Cooperation, National Center for Global Health and Medicine Institute for Global Health Policy Research, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhito","family":"Uezono","sequence":"additional","affiliation":[{"name":"Jikei University School of Medicine Department of Pain Control Research, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-1971","authenticated-orcid":false,"given":"Hiromichi","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, National Cancer Center Japan Department of Psycho-Oncology, , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"2023090115563958700_ref1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1001\/jama.2010.1013","article-title":"Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis","volume":"304","author":"Witlox","year":"2010","journal-title":"JAMA"},{"key":"2023090115563958700_ref2","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1001\/jamaneurol.2020.2273","article-title":"Association of delirium with long-term cognitive decline: a meta-analysis","volume":"77","author":"Goldberg","year":"2020","journal-title":"JAMA Neurol"},{"key":"2023090115563958700_ref3","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/alz.12262","article-title":"The economic cost of delirium: a systematic review and quality assessment","volume":"17","author":"Kinchin","year":"2021","journal-title":"Alzheimers Dement"},{"key":"2023090115563958700_ref4","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/1472-6882-12-222","article-title":"The clinical use of Kampo medicines (traditional Japanese herbal treatments) for controlling cancer patients\u2019 symptoms in Japan: a national cross-sectional survey","volume":"12","author":"Iwase","year":"2012","journal-title":"BMC Complement Altern Med"},{"key":"2023090115563958700_ref5","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00268-018-4761-0","article-title":"Preoperative anxiety as a predictor of delirium in cancer patients: a prospective observational cohort study","volume":"43","author":"Wada","year":"2019","journal-title":"World J Surg"},{"key":"2023090115563958700_ref6","doi-asserted-by":"crossref","first-page":"iv143","DOI":"10.1093\/annonc\/mdy147","article-title":"Delirium in adult cancer patients: the ESMO clinical practice guidelines","volume":"29","author":"Bush","year":"2018","journal-title":"Ann Oncol"},{"key":"2023090115563958700_ref7","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","article-title":"Delirium in elderly people","volume":"383","author":"Inouye","year":"2014","journal-title":"Lancet"},{"key":"2023090115563958700_ref8","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.3390\/ijms14048638","article-title":"Melatonin: buffering the immune system","volume":"14","author":"Carrillo-Vico","year":"2013","journal-title":"Int J Mol Sci"},{"key":"2023090115563958700_ref9","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1023\/A:1015187601628","article-title":"Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting","volume":"21","author":"Zisapel","year":"2001","journal-title":"Cell Mol Neurobiol"},{"key":"2023090115563958700_ref10","doi-asserted-by":"crossref","first-page":"e1204","DOI":"10.1097\/CCM.0000000000003400","article-title":"A systematic review and meta-analysis examining the impact of sleep disturbance on postoperative delirium","volume":"46","author":"Fadayomi","year":"2018","journal-title":"Crit Care Med"},{"key":"2023090115563958700_ref11","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s00134-022-06638-9","article-title":"Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial","volume":"48","author":"Wibrow","year":"2022","journal-title":"Intensive Care Med"},{"key":"2023090115563958700_ref12","doi-asserted-by":"crossref","first-page":"c3704","DOI":"10.1136\/bmj.c3704","article-title":"Diagnosis, prevention, and management of delirium: summary of NICE guidance","volume":"341","author":"Young","year":"2010","journal-title":"BMJ"},{"key":"2023090115563958700_ref13","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/B978-0-12-819975-6.00022-4","article-title":"Melatonin receptors, brain functions, and therapies","volume":"179","author":"Oishi","year":"2021","journal-title":"Handb Clin Neurol"},{"key":"2023090115563958700_ref14","doi-asserted-by":"crossref","first-page":"19m12865","DOI":"10.4088\/JCP.19m12865","article-title":"Real-world effectiveness of ramelteon and suvorexant for delirium prevention in 948 patients with delirium risk factors","volume":"81","author":"Hatta","year":"2019","journal-title":"J Clin Psychiatry"},{"key":"2023090115563958700_ref15","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.sleep.2013.11.788","article-title":"Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis","volume":"15","author":"Kuriyama","year":"2014","journal-title":"Sleep Med"},{"key":"2023090115563958700_ref16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/icvts\/ivw297","article-title":"Efficacy of ramelteon for delirium after lung cancer surgery","volume":"24","author":"Miyata","year":"2017","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"2023090115563958700_ref17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s10388-017-0570-z","article-title":"Postoperative delirium after pharyngolaryngectomy with esophagectomy: a role for ramelteon and suvorexant","volume":"14","author":"Booka","year":"2017","journal-title":"Esophagus"},{"key":"2023090115563958700_ref18","doi-asserted-by":"crossref","first-page":"e0241673","DOI":"10.1371\/journal.pone.0241673","article-title":"Preventative effects of ramelteon against postoperative delirium after elective liver resection","volume":"15","author":"Hokuto","year":"2020","journal-title":"PloS One"},{"key":"2023090115563958700_ref19","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1007\/s00595-020-02073-9","article-title":"A phase II study of ramelteon for the prevention of postoperative delirium in elderly patients undergoing gastrectomy","volume":"50","author":"Honda","year":"2020","journal-title":"Surg Today"},{"key":"2023090115563958700_ref20","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1001\/jamapsychiatry.2018.4365","article-title":"Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta-analysis","volume":"76","author":"Wu","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"2023090115563958700_ref21","first-page":"51243","article-title":"Federal Register","author":"US Department of Justice Drug Enforcement Administration","year":"2014"},{"key":"2023090115563958700_ref22","first-page":"397","article-title":"Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA","volume":"71","author":"Hatta","year":"2014","journal-title":"Psychiatry"},{"key":"2023090115563958700_ref23","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1097\/CCM.0000000000003132","article-title":"Effect of administration of ramelteon, a melatonin receptor agonist, on the duration of stay in the ICU: a single-center a randomized placebo-controlled trial","volume":"46","author":"Nishikimi","year":"2018","journal-title":"Crit Care Med"},{"key":"2023090115563958700_ref24","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jagp.2020.05.006","article-title":"Effects of ramelteon on the prevention of postoperative delirium in older patients undergoing orthopedic surgery: the RECOVER randomized controlled trial","volume":"29","author":"Oh","year":"2021","journal-title":"Am J Geriatr Psychiatry"},{"key":"2023090115563958700_ref25","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1097\/CCM.0000000000004004","article-title":"Ramelteon for prevention of postoperative delirium: a randomized controlled trial in patients undergoing elective pulmonary thromboendarterectomy","volume":"47","author":"Jaiswal","year":"2019","journal-title":"Crit Care Med"},{"key":"2023090115563958700_ref26","first-page":"245","article-title":"Japan\u2019s advanced medicine","volume":"7","author":"Sho","year":"2013","journal-title":"Biosci Trends"},{"key":"2023090115563958700_ref27","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013","edition":"5th"},{"key":"2023090115563958700_ref28","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1248\/bpb.b17-00512","article-title":"Usefulness of two-compartment model-assisted and static overall inhibitory-activity method for prediction of drug-drug interaction","volume":"40","author":"Iga","year":"2017","journal-title":"Biol Pharm Bull"},{"key":"2023090115563958700_ref29","doi-asserted-by":"crossref","first-page":"S348","DOI":"10.1016\/j.jalz.2010.05.1166","article-title":"Japanese versions equivalent to original English neuropsychological tests in ADNI","volume":"6","author":"Sugishita","year":"2010","journal-title":"Alzheimers Dement"},{"key":"2023090115563958700_ref30","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.psym.2017.05.005","article-title":"Validation of a nurse-based delirium screening tool for hospitalized patients","volume":"58","author":"Hargrave","year":"2017","journal-title":"Psychosomatics"},{"key":"2023090115563958700_ref31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1176\/jnp.13.2.229","article-title":"Validation of the delirium rating scale revised-98: comparison with the delirium rating scale and the cognitive test for delirium","volume":"13","author":"Trzepacz","year":"2001","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"2023090115563958700_ref32","first-page":"425","article-title":"Japanese version of the Delirium Rating Scale, Revised-98 (DRS-R98-J): reliability and validity","volume":"51","author":"Kato","year":"2010","journal-title":"Psychosomatics"},{"key":"2023090115563958700_ref33","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jpainsymman.2015.05.014","article-title":"Validation of the Japanese version of the Edmonton symptom assessment system-revised","volume":"50","author":"Yokomichi","year":"2015","journal-title":"J Pain Symptom Manage"},{"key":"2023090115563958700_ref34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0165-1781(00)00232-8","article-title":"Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects","volume":"97","author":"Doi","year":"2000","journal-title":"Psychiatry Res"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/53\/9\/851\/51308815\/hyad061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/53\/9\/851\/51308815\/hyad061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T15:57:19Z","timestamp":1693583839000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/53\/9\/851\/7203936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,20]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,6,20]]},"published-print":{"date-parts":[[2023,8,30]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyad061","relation":{},"ISSN":["1465-3621"],"issn-type":[{"type":"electronic","value":"1465-3621"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,6,20]]}}}