STUDY PROTOCOL Open Access Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: study protocol of a cluster randomized trial Isabel del Cura-González 1,2,3,4,5* , Juan A. López-Rodríguez 1,2,3,4,5,6 , Francisca Leiva-Fernández 3,5,7,8,9 , Luis A. Gimeno-Feliu 3,5,10,11,12 , Victoria Pico-Soler 3,5,12,13 , Mª. Josefa Bujalance-Zafra 7,14 , Miguel Domínguez-Santaella 7,14 , Elena Polentinos-Castro 1,2,3,4,5 , Beatriz Poblador-Plou 3,5,12 , Paula Ara-Bardají 3,5,12 , Mercedes Aza-Pascual-Salcedo 3,5,12,15 , Marisa Rogero-Blanco 3,4,5,6 , Marcos Castillo-Jiménez 7,16 , Cristina Lozano-Hernández 1,3,5,17 , Antonio Gimeno-Miguel 3,5,12 , Francisca González-Rubio 3,5,12,18 , Rodrigo Medina-García 1,4,5,6,17 , Alba González-Hevilla 7 , Mario Gil-Conesa 19 , Jesús Martín-Fernández 2,3,4,5,20 , José M. Valderas 21 , Alessandra Marengoni 22 , Christiane Muth 23 , J. Daniel Prados-Torres 3,5,7,8,9† , Alexandra Prados-Torres 3,5,12† and MULTIPAP PLUS Group Abstract Background: The progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process. Objective: To assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care. Methods/design: This is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient. © The Author(s). 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. * Correspondence: Isabel.cura@salud.madrid.org † J. Daniel Prados-Torres and Alexandra Prados-Torres share senior co-authorship. 1 Research Unit, Primary Care Assistance Management, Madrid Health Service, Madrid, Spain Full list of author information is available at the end of the article del Cura-González et al. Trials (2022) 23:479 https://doi.org/10.1186/s13063-022-06293-x