ObjectiveTo determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.DesignEvaluator blinded, randomised controlled trial.Setting16 clinical sites across 11 European countries, January 2016 to 31 October 2019.Participants1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).InterventionsThe multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.Main outcome measuresThe primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes.ResultsMean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34).ConclusionsA multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.Trial registrationClinicalTrials.gov NCT02582138.

translation represents other major barriers to innovations in geriatrics [5].The Innovative Medicines Initiative-Joint Undertaking (IMI-JU), a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA), is strategically equipped to foster the research in areas where there is an unmet medical or social need by supporting collaborative efforts of academic and industrial partners (https:// www.imi.europa.eu/). Within the ninth call for proposals launched by IMI-JU in 2013, the agency identified physical frailty and sarcopenia (PF&S) as prototype geriatric conditions on which to leverage for advancing the care of older people with unmet needs. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) project has been designed to produce significant advancements in the management of older persons with PF&S by promoting a consensus among academia, regulators, industry, and patients' representatives over (1) a clear operationalization of frailty; (2) the identification of a precise target population with unmet medical needs; (3) the evaluation and validation of a new methodology for implementing in Europe preventive and therapeutic strategies among frail elders at risk of disability; (4) the definition of an experimental setting serving as template for regulatory purposes and pharmaceutical investigations; and (5) the identification of biomarkers and health technology solutions to be implemented in clinical practice [6]. To ensure the successful accomplishment of the project goals, a consortium has been established convening experts in PF&S, trial methodology, biomarker discovery and qualification, health technology assessment, information and communication technology (ICT) solutions, regulatory affairs, and dissemination. The consortium is organized in multiple interacting work-package teams, reassemblingThe absolute and relative number of people aged 65+ is on a sharp rise worldwide [1]. Such a demographic transition is certainly a desirable result of the magnificent combination of socioeconomic development, technological, and medical advancements, and the establishment of solid public health systems. On the other hand, population aging brings forth substantial challenges for healthcare providers, policy makers, and regulators [2]. Indeed, existing healthcare systems, built around the traditional "standalone disease medicine" paradigm, are not equipped to address the complex medical needs of a growing share of the population characterized by multimorbidity and disabilities [3]. As a consequence, a substantial number of older adults do not receive the health services they would need for maximizing their function and quality of life [4]. At the same time, the suboptimal use of resources results in escalating costs which poses a serious threat to the sustainability of health and social care systems. To further complicate the matter, the existence of regulatory gaps hampers the development of innovativ...