{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:49:38Z","timestamp":1785761378000,"version":"3.56.0"},"reference-count":22,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"unspecified","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP22\/00055"],"award-info":[{"award-number":["PMP22\/00055"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Plataforma Espa\u00f1ola de Investigaci\u00f3n Cl\u00ednica y Ensayos Cl\u00ednicos, SCReN"},{"name":"European Regional Development Fund\/European Social Fund"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,3,10]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"\n Introduction<\/jats:title>\n Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as tacrolimus, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policymakers. The iPHARMGx Consortium addresses this by developing the TRANSPGx clinical trial to assess the hypothesis that widespread adoption of a pre-emptive genotyping scheme in populations susceptible to receiving tacrolimus as immunosuppressive therapy following a kidney transplant is effective, cost-effective and feasible within the Spanish National Health System (SNHS) when compared to the standard of care tacrolimus dosing.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n The TRANSPGx trial is a multicentre, adaptive, randomised, controlled, pragmatic phase IV clinical trial nested within the iPHARMGx master protocol, with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach, with stratification by centre. After inclusion in the trial and completion of genotyping, subjects will be randomly allocated to either the experimental group (pharmacogenetic genotype-guided tacrolimus prescription) or the standard of care tacrolimus prescription (as deemed by the attending physician). The primary objective is to assess the effectiveness of a tacrolimus pre-emptive genotyping strategy in reaching tacrolimus target plasma concentrations after renal transplant. A total of 114 subjects will be recruited among the different participating centres, provided that no futility\/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period, and subjects will be followed for a 6-month period.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n \n The TRANSPGx trial received ethical approval on 16 January 2025 (La Paz University Hospital 2024.740). Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication. Trial registration of this study can be located at both the EU Clinical Trials Register, available from\n https:\/\/euclinicaltrials.eu\/search-for-clinical-trials\/?lang=en<\/jats:ext-link>\n and\n https:\/\/clinicaltrials.gov<\/jats:ext-link>\n . Registration on both websites was done before the enrolment of the first patient complying with European regulations. The EU Clinical Trials Register is a primary registry according to the WHO.\n <\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n EU CT number: 2024\u20135 16 596-32\u221200\/Clinical trial Identifier (ClinicalTrials.gov):\n NCT06701825<\/jats:ext-link>\n . Protocol V. 1.2, 8 January 2025.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-109279","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:05:52Z","timestamp":1785758752000},"page":"e109279","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Multicentre, controlled, randomised and single-blind, adaptive phase IV protocol to evaluate effectiveness and cost-effectiveness of a pre-emptive genotyping strategy to optimise tacrolimus dosage in a pretransplant chronic kidney disease population cohort: iPHARMGx TRANSPGx nested clinical trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06701825","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Enrique","family":"Seco-Meseguer","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department, La Paz University Hospital IdiPAZ, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Stewart","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, La Paz University Hospital IdiPAZ, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Diago-Sempere","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, La Paz University Hospital IdiPAZ, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Nephrology Department, La Paz University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Mac\u00edas Carmona","sequence":"additional","affiliation":[{"name":"Nephrology Department Hospital General, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fern\u00e1ndez Sol\u00eds","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitario de Canarias, San Crist\u00f3bal de La Laguna, Spain"},{"name":"Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna, San Crist\u00f3bal de La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vila Santandreu","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitari Germans Trias I Pujol-IGTP, Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosal\u00eda","family":"Valero San Cecilio","sequence":"additional","affiliation":[{"name":"Nephrology Department, Marqu\u00e9s de Valdecilla University Hospital, Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"L\u00f3pez Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Nephrology Department, Universidad de M\u00e1laga, Instituto Biom\u00e9dico de Investigaci\u00f3n de M\u00e1laga (IBIMA)-Plataforma BIONAND, Hospital Regional Universitario de M\u00e1laga, M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Carmona-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Agency, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"(RICAPPS), Research Network on Chronicity Primary Care and Prevention and Health Promotion, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A","family":"L\u00f3pez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"Plataforma SCReN, Plataforma SCReN, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-4194","authenticated-orcid":false,"given":"I\u00f1aki","family":"Imaz-Iglesia","sequence":"additional","affiliation":[{"name":"(RICAPPS), Research Network on Chronicity Primary Care and Prevention and Health Promotion, Barcelona, Spain"},{"name":"AETS, Instituto de Salud Carlos III, Health Technology Assessment Agency, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Mar","family":"Garc\u00eda-Saiz","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Service, Marqu\u00e9s de Valdecilla University Hospital, Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mag\u00ed","family":"Farr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology. Pharmacogenomics Unit, Hospital Germans Trias i Pujol, Badalona, Spain"},{"name":"Department of Pharmacology, Universitat Autonoma de Barcelona, Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Rodriguez-Jimenez","sequence":"additional","affiliation":[{"name":"UICEC del Complejo Hospitalario Universitario de Canarias. Clinical Pharmacology Service, Hospital Universitario de Canarias, La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Sanabria-Cabrera","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Service, Clinical Research Unit and Clinical Trials, Biomedical Research Institute of M\u00e1laga and Nanomedicine Platform (IBIMA Platform BIONAND), ISCIII Clinical Research Platform, Hospital Universitario Virgen de la Victoria, Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Rosas-Alonso","sequence":"additional","affiliation":[{"name":"IdiPAZ, Experimental Therapies and Novel Biomarkers in Cancer, La Paz University Hospital Health Research Institute, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Plataforma SCReN, Plataforma SCReN, Madrid, Spain"},{"name":"Pharmacology Department School of Medicine, Universidad Aut\u00f3noma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-3263","authenticated-orcid":false,"given":"Alberto M","family":"Borobia","sequence":"additional","affiliation":[{"name":"Plataforma SCReN, Plataforma SCReN, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"2026080305052226000_16.8.e109279.1","doi-asserted-by":"crossref","unstructured":"Cocco A , Shahrestani S , Cocco N , et al . Dual kidney transplant techniques: A systematic review. Clin Transplant 2017;31. doi:10.1111\/ctr.13016","DOI":"10.1111\/ctr.13016"},{"key":"2026080305052226000_16.8.e109279.2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/ajt.12579","article-title":"OPTN\/SRTR 2012 Annual Data Report: Kidney","volume":"14","author":"Matas","year":"2014","journal-title":"American Journal of Transplantation"},{"key":"2026080305052226000_16.8.e109279.3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.transproceed.2019.11.003","article-title":"Long-Term Kidney Transplant Outcomes: Role of Prolonged-Release Tacrolimus","volume":"52","author":"Banas","year":"2020","journal-title":"Transplant Proc"},{"key":"2026080305052226000_16.8.e109279.4","doi-asserted-by":"publisher","DOI":"10.4103\/ijn.IJN_278_20"},{"key":"2026080305052226000_16.8.e109279.5","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.38"},{"key":"2026080305052226000_16.8.e109279.6","doi-asserted-by":"publisher","DOI":"10.1177\/106002809402800414"},{"key":"2026080305052226000_16.8.e109279.7","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.transproceed.2016.02.081","article-title":"Higher Variability of Tacrolimus Trough Level Increases Risk of Acute Rejection in Kidney Transplant Recipients","volume":"48","author":"Huang","year":"2016","journal-title":"Transplant Proc"},{"key":"2026080305052226000_16.8.e109279.8","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008680"},{"key":"2026080305052226000_16.8.e109279.9","doi-asserted-by":"publisher","DOI":"10.2174\/1389200219666180129151948"},{"key":"2026080305052226000_16.8.e109279.10","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0120-3"},{"key":"2026080305052226000_16.8.e109279.11","doi-asserted-by":"publisher","DOI":"10.1038\/86882"},{"key":"2026080305052226000_16.8.e109279.12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s12519-017-0035-4","article-title":"Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies","volume":"13","author":"Zong","year":"2017","journal-title":"World J Pediatr"},{"key":"2026080305052226000_16.8.e109279.13","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.113"},{"key":"2026080305052226000_16.8.e109279.14","doi-asserted-by":"crossref","DOI":"10.1186\/s12882-023-03188-0","article-title":"Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation","volume":"24","author":"Nguyen","year":"2023","journal-title":"BMC Nephrol"},{"key":"2026080305052226000_16.8.e109279.15","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12526"},{"key":"2026080305052226000_16.8.e109279.16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41397-022-00272-w","article-title":"A systematic review on the cost effectiveness of pharmacogenomics in developing countries: implementation challenges","volume":"22","author":"Sukri","year":"2022","journal-title":"Pharmacogenomics J"},{"key":"2026080305052226000_16.8.e109279.17","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1463384","article-title":"Editorial: State of the science of pharmacogenomics implementation in healthcare systems and communities","volume":"15","author":"David","year":"2024","journal-title":"Front Pharmacol"},{"key":"2026080305052226000_16.8.e109279.18","doi-asserted-by":"publisher","DOI":"10.2165\/11537410-000000000-00000"},{"key":"2026080305052226000_16.8.e109279.19","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-089823","article-title":"Phase IV adaptive randomised clinical trials evaluating efficacy and cost-efficacy of pre-emptive pharmacogenetic genotyping strategies in the Spanish National Health System: iPHARMGx Master Protocol and PREVESTATGx nested clinical trial","volume":"14","author":"Stewart","year":"2024","journal-title":"BMJ Open"},{"key":"2026080305052226000_16.8.e109279.20","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-3-201302050-00583"},{"key":"2026080305052226000_16.8.e109279.21","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v066.i05)"},{"key":"2026080305052226000_16.8.e109279.22","doi-asserted-by":"crossref","DOI":"10.1111\/petr.13285","article-title":"A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation","volume":"22","author":"Min","year":"2018","journal-title":"Pediatr Transplant"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-109279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:05:55Z","timestamp":1785758755000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-109279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,3]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/bmjopen-2025-109279"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-109279","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}