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 (Hospital Universitario La Paz (Madrid))
Seco-Meseguer, Enrique (Hospital Universitario La Paz (Madrid))
Diago-Sempere, Elena (Hospital Universitario La Paz (Madrid))
Marín-Candón, Alicia (Hospital Universitario La Paz (Madrid))
Carmona, Montserrat (Instituto de Salud Carlos III)
Estébanez, Miriam (Hospital Central de la Defensa Gómez Ulla)
López-Fernández, Luis A. (Universitario Gregorio Marañón)
Imaz-Iglesia, Iñaki (Red de Investigación en Servicios de Salud en Enfermedades Crónicas (Madrid))
del Mar García Saiz, María (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Laserna-Mendieta, Emilio J. (Instituto de Investigación Sanitaria de Castilla La Mancha)
Peiró Ibañez, Ana M. (Hospital General Universitario de Alicante (Alacant, País Valencià))
Farré Albaladejo, Magí (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Rodriguez-Jimenez, Consuelo (UICEC)
Saiz-Rodriguez, Miriam (Hospital Universitario de Burgos)
Sanabria-Cabrera, Judith (Hospital Clinico Universitario Virgen de la Victoria (Màlaga))
Rosas-Alonso, Rocío (Hospital Universitario La Paz (Madrid))
Abad-Santos, Francisco (Hospital Universitario de la Princesa (Madrid))
Pedrosa, Lucia (Instituto de Salud Carlos III)
Carcas, Antonio J. (Hospital Universitario La Paz (Madrid))
García García, Irene (Hospital Universitario La Paz (Madrid))
Borobia, Alberto M. (Universidad Autónoma de Madrid)

Date:	2024
Abstract:	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. 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. 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. EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials. gov): . 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 and . 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	CLINICAL PHARMACOLOGY ; Lipid disorders ; PUBLIC HEALTH ; Clinical Trial ; GENETICS
Published in:	BMJ open, Vol. 14 (november 2024) , ISSN 2044-6055

DOI: 10.1136/bmjopen-2024-089823
PMID: 39510769

13 p, 879.3 KB

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