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00925njm 22002777a 4500 dc Stewart, Stefan author Seco-Meseguer, Enrique author Diago-Sempere, Elena author Marín-Candón, Alicia author Carmona, Montserrat author Estébanez, Miriam author López-Fernández, Luis A author Imaz-Iglesia, Iñaki author Del Mar García Saiz, María author Laserna-Mendieta, Emilio J author Peiró, Ana M author Farré, Magí author Rodriguez-Jimenez, Consuelo author Saiz-Rodriguez, Miriam author Sanabria-Cabrera, Judith author Rosas-Alonso, Rocío author Abad-Santos, Francisco author Pedrosa-Pérez, Lucía author Carcas, Antonio J author García García, Irene author Borobia, Alberto M author iPHARMGx study group author 2024-11-07 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. Stewart S, Seco-Meseguer E, Diago-Sempere E, Marín-Candón A, Carmona M, Estébanez M, López-Fernández LA, Imaz-Iglesia I, Del Mar García Saiz M, Laserna-Mendieta EJ, Peiró AM, Farré M, Rodriguez-Jimenez C, Saiz-Rodriguez M, Sanabria-Cabrera J, Rosas-Alonso R, Abad-Santos F, Pedrosa L, Carcas AJ, García García I, Borobia AM; iPHARMGx study group. 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. BMJ Open. 2024 Nov 7;14(11):e089823. 10.1136/bmjopen-2024-089823 2044-6055 BMJ open 39510769 https://hdl.handle.net/20.500.12105/26625 Clinical-Pharmacology Clinical Trial Genetics Lipid disorders Public health 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