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
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...
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2024-11-01
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| author | Xandra García-González Alberto M Borobia Antonio J Carcas Miriam Estébanez Montserrat Carmona Irene García García Francisco Abad-Santos Luis A López-Fernández Esther Cubo Iñaki Imaz-Iglesia Alicia Marín-Candón Miriam Saiz-Rodríguez Irene Taladriz-Sender Pedro Arias Rocío Rosas-Alonso Enrique Seco-Meseguer Stefan Stewart Elena Diago-Sempere María del Mar García Saiz Emilio J Laserna-Mendieta Ana M Peiró Magí Farré Consuelo Rodriguez-Jimenez Judith Sanabria-Cabrera Lucia Pedrosa Ignacio Bernardino Javier Guiijarro-Eguinoa Arturo Gómez López De Las Huertas Susana Martín-López Olga Hladun Alvaro Vicente Arrate Ana Fries Daniel Rodriguez Díaz Fernando Marqués García Núria Alonso Pedrol Modesto M Maestre Muñiz Leticia Rodríguez Alcolado Carlos Ortiz-Bautista Angela Remesal-Doblado María Isabel Lucena Zaida Salmón González Inmaculada Coca-Prieto |
| author_facet | Xandra García-González Alberto M Borobia Antonio J Carcas Miriam Estébanez Montserrat Carmona Irene García García Francisco Abad-Santos Luis A López-Fernández Esther Cubo Iñaki Imaz-Iglesia Alicia Marín-Candón Miriam Saiz-Rodríguez Irene Taladriz-Sender Pedro Arias Rocío Rosas-Alonso Enrique Seco-Meseguer Stefan Stewart Elena Diago-Sempere María del Mar García Saiz Emilio J Laserna-Mendieta Ana M Peiró Magí Farré Consuelo Rodriguez-Jimenez Judith Sanabria-Cabrera Lucia Pedrosa Ignacio Bernardino Javier Guiijarro-Eguinoa Arturo Gómez López De Las Huertas Susana Martín-López Olga Hladun Alvaro Vicente Arrate Ana Fries Daniel Rodriguez Díaz Fernando Marqués García Núria Alonso Pedrol Modesto M Maestre Muñiz Leticia Rodríguez Alcolado Carlos Ortiz-Bautista Angela Remesal-Doblado María Isabel Lucena Zaida Salmón González Inmaculada Coca-Prieto |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fe076daeb0314b49a20a7cab8a12d654 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-fe076daeb0314b49a20a7cab8a12d6542025-01-20T00:50:12ZengBMJ Publishing GroupBMJ Open2044-60552024-11-01141110.1136/bmjopen-2024-089823Phase 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 0Xandra García-GonzálezAlberto M Borobia1Antonio J Carcas2Miriam Estébanez3Montserrat Carmona4Irene García García5Francisco Abad-Santos6Luis A López-Fernández7Esther CuboIñaki Imaz-Iglesia8Alicia Marín-Candón9Miriam Saiz-Rodríguez10Irene Taladriz-SenderPedro AriasRocío Rosas-Alonso11Enrique Seco-Meseguer12Stefan Stewart13Elena Diago-Sempere14María del Mar García Saiz15Emilio J Laserna-Mendieta16Ana M Peiró17Magí Farré18Consuelo Rodriguez-Jimenez19Judith Sanabria-Cabrera20Lucia Pedrosa21Ignacio BernardinoJavier Guiijarro-EguinoaArturo Gómez López De Las HuertasSusana Martín-LópezOlga Hladun AlvaroVicente ArrateAna FriesDaniel Rodriguez DíazFernando Marqués GarcíaNúria Alonso PedrolModesto M Maestre MuñizLeticia Rodríguez AlcoladoCarlos Ortiz-BautistaAngela Remesal-DobladoMaría Isabel LucenaZaida Salmón GonzálezInmaculada Coca-PrietoCancer Care Research and Engagement, UKPharmacology Department. School of Medicine, Autonomous University of Madrid, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainInternal Medicine Department, Hospital Central de la Defensa Gomez Ulla, Madrid, SpainHealth Technology Assessment Agency, Instituto de Salud Carlos III, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainUICEC Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IP), Hospital Universitario de la Princesa, Madrid, SpainPharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Maranon, Madrid, SpainHealth Technology Assessment Agency (AETS), Instituto de Salud Carlos III, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainResearch Unit, Fundación Burgos por la Investigación de la Salud, Hospital Universitario de Burgos, Burgos, SpainPharmacogenetics Laboratory, Genetics Department, Hospital Universitario La Paz, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainClinical Pharmacology Department, Hospital Universitario La Paz, Madrid, SpainClinical Pharmacology Service, Hospital Universitario Marques de Valdecilla, Santander, Cantabria, SpainDepartment of Gastroenterology, Research Unit, Hospital General de Tomelloso, Tomelloso, Castilla-La Mancha, SpainUnidad de Farmacología Clínica, Unidad del Dolor, Alicante Department of Health-General Hospital, Alicante, Comunidad Valenciana, SpainDepartment of Clinical Pharmacology, Pharmacogenomics Unit, Hospital Germans Trias i Pujol, Badalona, Catalunya, SpainClinical Trials Unit, Pharmacology Department, Hospital Universitario de Canarias, La Laguna, Canarias, SpainServicio de Farmacología Clínica, IBIMA Plataforma BIONAND, Universidad de Málaga, Málaga, Spain, Platform for Clinical Research and Clinical Trials IBIMA, Hospital Universitario Virgen de la Victoria, Malaga, Andalucía, SpainHealth Technology Assessment Agency (AETS), Instituto de Salud Carlos III, Madrid, SpainIntroduction 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.https://bmjopen.bmj.com/content/14/11/e089823.full |
| spellingShingle | Xandra García-González Alberto M Borobia Antonio J Carcas Miriam Estébanez Montserrat Carmona Irene García García Francisco Abad-Santos Luis A López-Fernández Esther Cubo Iñaki Imaz-Iglesia Alicia Marín-Candón Miriam Saiz-Rodríguez Irene Taladriz-Sender Pedro Arias Rocío Rosas-Alonso Enrique Seco-Meseguer Stefan Stewart Elena Diago-Sempere María del Mar García Saiz Emilio J Laserna-Mendieta Ana M Peiró Magí Farré Consuelo Rodriguez-Jimenez Judith Sanabria-Cabrera Lucia Pedrosa Ignacio Bernardino Javier Guiijarro-Eguinoa Arturo Gómez López De Las Huertas Susana Martín-López Olga Hladun Alvaro Vicente Arrate Ana Fries Daniel Rodriguez Díaz Fernando Marqués García Núria Alonso Pedrol Modesto M Maestre Muñiz Leticia Rodríguez Alcolado Carlos Ortiz-Bautista Angela Remesal-Doblado María Isabel Lucena Zaida Salmón González Inmaculada Coca-Prieto 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 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/14/11/e089823.full |
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