{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:34:40Z","timestamp":1765006480033,"version":"3.46.0"},"reference-count":35,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T00:00:00Z","timestamp":1702080000000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences","award":["2022-I2M-C&T-B-023"],"award-info":[{"award-number":["2022-I2M-C&T-B-023"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["2022-PUMCH-B-083"],"award-info":[{"award-number":["2022-PUMCH-B-083"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,11,30]]},"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bleomycin is a crucial and irreplaceable chemotherapy regimen for malignant ovarian germ cell tumours (MOGCTs) but its toxicities especially pulmonary fibrosis have limited the dose of treatment efficacy and decreased the patients\u2019 quality of life (QoL). Nintedanib has been approved for treating progressive fibrosing interstitial lung diseases and has shown potential anti-tumour effects. This study aims to evaluate the effectiveness and safety of nintedanib in the prevention of pulmonary fibrosis induced by bleomycin in MOGCTs patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. We will enrol a total of 128 patients who will be randomly assigned to the nintedanib group and placebo group in a 1:1 ratio. Standard bleomycin, etoposide and cisplatin chemotherapy will be given to each MOGCT patient. In addition, patients assigned to nintedanib and the control group will be given oral nintedanib 150\u2009mg two times per day and placebo one tablet two times per day until 1\u2009month after the last cycle of bleomycin therapy, respectively. The primary outcome is the decline of forced vital capacity (FVC). The secondary outcomes are the decline of other pulmonary function indices (forced expiratory volume in 1\u2009s; FVC pred%, carbon monoxide diffusion capacity) and the patients\u2019 QoL, oncological and fertility outcomes. We will use electronic case report forms to record all the participants\u2019 data and SPSS V.27.0\/STATA V.16.0\/Graphpad Prism V.8.0 to conduct statistical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The Ethics Committee of Peking Union Medical College Hospital has approved the study (I-23PJ400). Written informed consent will be obtained from all participants\/guardians. Study results will be submitted to peer-reviewed medical journals for publication and presented at academic conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2300070492.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-074963","type":"journal-article","created":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T11:27:58Z","timestamp":1702207678000},"page":"e074963","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness and safety of nintedanib in prevention of pulmonary fibrosis induced by bleomycin in malignant ovarian germ cell tumour: study protocol for a randomised, double-blind, placebo-controlled trial"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1578-0516","authenticated-orcid":false,"given":"Sijian","family":"Li","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yin","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Beijing, China"},{"name":"Department of Gynecology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rundong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union 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