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
Authors: del Cura-González Isabel , López-Rodríguez Juan A. , Leiva-Fernández Francisca , Gimeno-Feliu Luis A. , Pico-Soler Victoria , Bujalance-Zafra Mª. Josefa , Domínguez-Santaella Miguel , Polentinos-Castro Elena , Poblador-Plou Beatriz , Ara-Bardají Paula , Aza-Pascual-Salcedo Mercedes , Rogero-Blanco Marisa , Castillo-Jiménez Marcos , Lozano-Hernández Cristina , Gimeno-Miguel Antonio , González-Rubio Francisca , Medina-García Rodrigo , González-Hevilla Alba , Gil-Conesa Mario , Martín-Fernández Jesús , Valderas José M. , Marengoni Alessandra , Muth Christiane , Prados-Torres J. Daniel , Prados-Torres Alexandra ,   MULTIPAP PLUS Group, Orellana-Lozano Francisco Javier , Sepúlveda-Muñoz Jesús , Sánchez-Jordán Rafael , Escobar-Pérez Amparo , Rodríguez-García Concepción , Peñuela-Ruiz Trinidad , Navarro-Martín José Antonio , Rodríguez-Rivera María Rosario , Aguilar-Heredia Yolanda , Martínez-Sarmiento Antonio Ignacio , Pascual-de-la-Pisa Beatriz , García-Lozano María José , García-Carrera Alejandro , Juan-Tordesillas Noelia , Márquez-Chamizo María Isabel , Navarro-Jiménez José Manuel , Ruiz-Ciudad María Carmen , Vázquez-Alarcón Rubén Luciano , Navarro-Gallego María Isabel , Ginel-Mendoza Leovigildo , Ruiz-San-Basilio José María , Barceló-Garach Elena , Alcantarilla-Reyes Elisa María , de Cienfuegos Hernández Marta Álvarez , Martínez-Ríos Irene , Orellana-Martín Laura , Merino-Moyano María Dolores , Segura-Domínguez Nuria , Moral-Merchán María Cristina , Martín-Aurioles Esther , Rodríguez-González María Inmaculada , Hazañas-Ruiz Sylvia , Gallego-Castillo Eva Noelia , Mora-García Esperanza , Cámara-Sola Estefanía , Fons-Cañizares Sergio , Ortigosa-Arrabal María Paz , Quesada-Fernández Teresa , Rodríguez-Moreno Silvia , Sánchez-Silvestre Ana , Torrubia-Fernández María Jesús , González-Vega María José , Almagro-Martín-Lomeña María Victoria , Serrano-González Caridad , Leiva-Fernández José , Castillo-Romero Virginia , Fernández-Vargas Ana María , Serrano-Guerra Francisco José , Narbona-Carrión Gabriel Francisco , Michel-Bertevas Hervé , Maqueda Rafael Ángel , Domínguez-Santaella Miguel , García-Agua-Soler Nuria , del Pilar Barnestein-Fonseca Maria , Abadía-Taira María Begoña , Sánchez-Celaya-del-Pozo Carmen , Giménez-Baratech Ana Carmen , Sanz-Burgos Lara , Abad-Royo Mercedes , Camats-Franco Carmen , Cortés-Pellicer José Manuel , Herrero-Solsona Paula , Moreno-Juste Aida , Guiu-Campos Miguel , Peyman-Fard-Shafi-Tabatabaei Nima , Delgado-Marroquín Ma Teresa , López-Echevarría Mercedes , Carmona-Pírez Jonás , Barrera-Linares Fernando , Carrillo-Soria Sandro Daniel , Esteban-Gimeno Ana Belén , López-Alonso Beatriz , Hernández-Bono Anabel , Martínez-Ayala Enrique , Martínez-Manero Adriana , Martínez-Sánchez Raquel , Naya-Mateu Yolanda , Clemente-Jiménez María Lourdes , Leon-Martínez María Paz , Mahuela Liliana , Sanjuan-Cortés Ma Rosario , Salazar-González Elisa Pilar , Charte-Alegre Ma Elena , Mur-Lazuela Ma Jesús , Pascual-Franco Mónica , Arizon-Deza Pilar , García-Gutiérrez-Muñoz Carmen , García-Ruiz Teresa , Navarro-Aznárez Gloria , Alcober-Pérez Carlos , Navarro-Tausiet María Paz , Lacasa-Serrano Ma Elena , Maza-Invernón Ana Cristina , Peleato-Sánchez Jaime , Buñuel-Granados José Miguel , Alonso-Valbuena Ainara , Lasheras-Barrio Mónica , Ibarrondo-Fernández-Ladreda Isabel , López-Aylon Rosa Ma , Rodríguez-Fabre María José , Rubio-Gutiérrez Isabel , Valverde-Aranda Selma , Bandrés-Liso Ana Cristina , Poncel-Falcó Antonio , Bliek-Bueno Kevin , Cano-del-Pozo Mabel , Clerencia-Sierra Mercedes , Díez-Manglano Jesús , Guerrero-Fernández-de-Alba Inmaculada , Ioakeim-Skoufa Ignatios , Marta-Moreno Javier , Santos-Muñoz David , Viñuela-Benéitez María Elisa , Miguel-Abanto María De Los Angeles , García-De-Blas Francisca , García-Álvarez Juan Carlos , Redondo-de-Pedro Sonia , González-García Carlos Fernando , Peláez-Laguno Carolina , Gomez-Suarez Esther , Morales-Ortiz Fernanda , Ferrer-Zapata Isabel , Sánchez-Fernández Yolanda Beatriz , Fernández-Fernández Yolanda , Barrio-Higelmo Esther , Rioja-Delgado Eva María , Lopez-Larrayoz Irina , Seara-Lozano María Luz , Fernández-Sánchez Julio Cesar , San-Miguel-Marinero María Teresa , Fidalgo-Baz María Jesus , Ares-Blanco Sara , Gómez-Ciriano Jorge Ignacio , Garcés-Ranz José Damián , Santos-Franco Laura , García-Galeano María Celeste , Mateo-Fernández Raquel , Morcillo-Cebolla Sara , Rossignoli-Fernández Tomás , Olmedo-Galindo Jorge , Pinel-González Marta , Redondo-Romero Rosa María , Estrada-Leon Adnaloy Helena , Muñoz-Gómez Belén , Sanz-Pozo Blanca , López-Marcos Claudia , Rodríguez-De-Mingo Enrique , Moreno-Fernández Juan Carlos , Morales-Cobos Luis Enrique , Garcia-Garcia-Alcañiz María Del Prado , Lorenzo-Borda Marisol , González-García Vera , Muñoz-Molina María Del Pilar , Drak-Hernández Yasmin , Rabanal-Basalo Alejandro , Abad-Esteban Ana María , Rollan-Hernández María De Los Ángeles , Fuster-Tozer Mónica , Carretero-Ramos Raquel , Mielgo-Salvador Rebeca , Sosa-Alonso Ana , Muros-Muñoz Carmen María , Sánchez-Yépez Jeannet Dolores , Cáceres-Cortés María Cristina , Morso-Peláez María Paloma , Pastor-Estebanez María , Fernández-Girón Mercedes , Pérez-De-Colosia-Zuil Antonia , Pérez-Gutiérrez Esteban , Tejero-García Isabel , Innerarity-Martínez Jaime , Álvarez-Villalba Mar , Gómez-Barroso Margarita , Escobar-Gallegos María Del Mar , Bedoya-Frutos María Jesus , Del-Olmo-Ribagorda Marta Inmaculada , Cortés-Durán Petra María , Tardáguila-Lobato Pilar , Terrón-Barbosa Raquel Yolanda , Ramos-Blanco Antonio , López-Villalvilla Aránzazu , Cinta-Bella Beatriz , Varela-Varela Cristian , Garcia-Rodriguez Francisca , Saiz-Ladera Gema María , López-Fernández Guillermina , Orozco-Barrenechea Lourdes , Zafra-De-Gea María Begoña , García-Arpa Nuria , Ewa-Barnas Tamara , Carbonero-Martín Ana Isabel , Rojas-Giraldo María José , Cotillas-Rodero Alberto , López-Serrano Beatriz , Rodriguez-Fernández María Del Carmen , Sanz-Velasco Carmelina , Aza-Pascual-Salcedo Jose Ignacio , Lopez-Olmeda Carolina , Gutiérrez-Ocana Estrella , García-Ocaña Raquel , Sanz-Cuesta Teresa , Rodríguez-Barrientos Ricardo , Rico-Blázquez Milagros , Ariza-Cardiel Ma Gloria , Mataix-San-Juan Angel , Alcaraz-Borrajo Marta , Rumayor-Zarzuelo Mercedes , Sánchez-Perruca Luis , Azcoaga-Lorenzo Amaya , Hernández-Santiago Virginia , Rotaeche-del-Campo Rafael 
Published: June 2022

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.

Population
Patients aged 65–74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included.

Sample size
n = 1148 patients (574 per study arm).

Intervention
Complex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system.

Outcomes
The primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables.

Statistical analysis
The main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle.

Discussion
It is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care.

Trial registration
ClinicalTrials.gov NCT04147130. Registered on 22 October 2019