{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:55:10Z","timestamp":1793663710235,"version":"4.5.1"},"reference-count":33,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw","award":["10140252110025"],"award-info":[{"award-number":["10140252110025"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,10]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are considered to have a symptomatic venous thromboembolism (VTE) risk of 1.0%\u20131.5% despite thromboprophylaxis. Fast-track treatment protocols have substantially lowered the VTE risk in most patients. Hence, the majority of patients may be unnecessarily exposed to the burden and risk of thromboprophylaxis. On the contrary, there are still patients with a high VTE risk who develop VTE despite thromboprophylaxis. Thus, tailored thromboprophylaxis treatment may potentially reduce both VTE and bleeding risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The DISTINCT (inDividual, targeted thrombosIS prophylaxis versus the standard \u2018one-size-fits-all\u2019 approach in patients undergoing Total hIp or total kNee replaCemenT) trial is a national, multicentre, randomised, multiarm, open-label trial. The main objective is to study whether tailored thromboprophylaxis reduces the occurrence of symptomatic VTE (primary outcome) and major bleeding (primary safety outcome) within 90 days after THA\/TKA in comparison with standard thromboprophylaxis. Patients with a low, intermediate or high predicted VTE risk (based on the Thrombosis Risk Prediction following total hip and knee arthroplasty score (TRiP(plasty) score)) will be included in the DISTINCT-1, DISTINCT-2 or DISTINCT-3 studies, respectively. In the DISTINCT-1 trial, 3478 patients will be randomly allocated to receive either in-hospital thromboprophylaxis or standard prophylaxis. In the DISTINCT-2 cohort study, 2500 patients will receive standard prophylaxis. In the DISTINCT-3 trial, 4100 patients will be randomly allocated to receive either 6\u2009weeks of high-dose thromboprophylaxis or standard prophylaxis. Standard prophylaxis consists of a low dose of any approved thromboprophylactic agent for 4\u2009weeks. We hypothesise that (1) the efficacy of in-hospital only thromboprophylaxis is non-inferior in preventing VTE and equally safe compared with standard prophylaxis in patients with a low VTE risk (DISTINCT-1) and (2) prolonged high-dose thromboprophylaxis is superior in preventing VTE as compared with standard prophylaxis in patients with a high VTE risk (DISTINCT-3). Patients with intermediate VTE risk will be observed to evaluate VTE and bleeding rates (DISTINCT-2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The protocol has been approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft, EU-trial-number 2023-510186-98. Study results will be disseminated through peer-reviewed journals and during international conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06581965\">NCT06581965<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-101180","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T07:40:51Z","timestamp":1759822851000},"page":"e101180","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Study protocol for the DISTINCT trial: inDividual, targeted thrombosIS prophylaxis versus the standard \u2018one-size-fits-all\u2019 approach in patients undergoing Total hIp or total kNee replaCemenT \u2013 a national, multicentre, randomised, multiarm, open-label trial"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06581965","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06581965","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7849-6195","authenticated-orcid":false,"given":"Ruben Y","family":"Kok","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leti","family":"van Bodegom-Vos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmen B","family":"Ettema","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Isala Klinieken, Zwolle, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf H H","family":"Groenwold","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbert B","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno V","family":"Huisman","sequence":"additional","affiliation":[{"name":"Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederikus A","family":"Klok","sequence":"additional","affiliation":[{"name":"Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob G H H","family":"Nelissen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke","family":"van Rein","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-4984","authenticated-orcid":false,"given":"Merel","family":"van Veen","sequence":"additional","affiliation":[{"name":"Dutch Hip Patient association 'Vereniging Afwijkende Heupontwikkeling (VAH)\u2019, Nijkerk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan B W","family":"Vehmeijer","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Reinier Haga Orthopedisch Centrum, Zoetermeer, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Joost I","family":"Wiegerinck","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Bergman Clinics Musculoskeletal Division, Naarden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-2303","authenticated-orcid":false,"given":"Suzanne C","family":"Cannegieter","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Department of Medicine - 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