2026-07-18T20:35:34Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/119172026-07-17T00:05:30Zcom_10259_11209com_10259_5086com_10259_2604col_10259_11210

2026-07-16T10:38:30Z urn:hdl:10259/11917 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 Stewart, Stefan Seco-Meseguer, Enrique Diago-Sempere, Elena Marín-Candón, Alicia Carmona, Montserrat Estébanez, Miriam López-Fernández, Luis A Imaz-Iglesia, Iñaki del Mar García Saiz, María Laserna-Mendieta, Emilio J Peiró, Ana M Farré, Magí Rodriguez-Jimenez, Consuelo Saiz-Rodriguez, Miriam Sanabria-Cabrera, Judith Rosas-Alonso, Rocío Abad-Santos, Francisco Pedrosa, Lucia Carcas, Antonio J García García, Irene Borobia, Alberto M Introduction 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 statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug–gene–population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial. Methods and analysis the PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if 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 9-month period. Ethics and dissemination The PREVESTATGx trial received ethical approval on 24 April 2024. 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 number EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO. 2026-07-16T10:38:30Z 2026-07-16T10:38:30Z 2024-11 info:eu-repo/semantics/article 2044-6055 https://hdl.handle.net/10259/11917 10.1136/bmjopen-2024-089823 2044-6055 eng BMJ Open. 2024, V. 14, n. 11, art. 089823 https://doi.org/10.1136/ bmjopen-2024-089823 http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Atribución-NoComercial 4.0 Internacional BMJ