Background: Muscle mass and physical function (PF) are common co-primary endpoints in cancer cachexia trials, but there is a lack of data on how these outcomes interact over time. The aim of this secondary analysis of data from a trial investigating multimodal intervention for cancer cachexia (ClinicalTrials.gov: NCT01419145) is to explore whether changes in muscle mass and PF are associated with weight loss and cachexia status at baseline. Methods: Secondary analysis was conducted using data from a phase II randomized controlled trial including 46 patients with stage III–IV non-small cell lung cancer (n = 26) or inoperable pancreatic cancer (n = 20) due to commence chemotherapy. Cachexia status at baseline was classified according to international consensus. Muscle mass (assessed using computed tomography (CT)) and PF outcomes, i.e., Karnofsky performance status (KPS), self-reported PF (self-PF), handgrip strength (HGS), 6-minute walk test (6MWT), and physical activity (PA), were measured at baseline and after six weeks. Results: When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (−5.3 cm2, p = 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (−2.8 cm2, p = 0.146), but demonstrated a statistically significant decline in PF; KPS (−3.8 points, p = 0.030), self-PF (−8.8 points, p = 0.027), and HGS (−2.7 kg, p = 0.026). Conclusions: Weight loss history and cachexia status at baseline are of importance if one aims to detect changes in PF outcomes in cancer cachexia trials. To improve the use of co-primary endpoints that include PF in future trials, outcomes that have the potential to detect change relative to weight loss should be investigated further.

IntroductionMultimodal interventions have emerged as new approaches to provide more targeted intervention to reduce functional decline after stroke. Still, the evidence is contradictory. The main objective of the Life After Stroke (LAST)-long trial is to investigate if monthly meetings with a stroke coordinator who offers a multimodal approach to long-term follow-up can prevent functional decline after stroke.Methods and analysisLAST-long is a pragmatic single-blinded, parallel-group randomised controlled trial recruiting participants living in six different municipalities, admitted to four hospitals in Norway. The patients are screened for inclusion and recruited into the trial 3 months after stroke. A total of 300 patients fulfilling the inclusion criteria will be randomised to an intervention group receiving monthly follow-up by a community-based stroke coordinator who identifies the participants’ individual risk profile and sets up an action plan based on individual goals, or to a control group receiving standard care. All participants undergo blinded assessments at 6-month, 12-month and 18-month follow-up. Modified Rankin Scale at 18 months is primary outcome. Secondary outcomes are results of blood tests, blood pressure, adherence to secondary prophylaxis, measures of activities of daily living, cognitive function, physical function, physical activity, patient reported outcome measures, caregiver’s burden, the use and costs of health services, safety measures and measures of adherence to the intervention. Mixed models will be used to evaluate differences between the intervention and control group for all endpoints across the four time points, with treatment group, time as categorical covariates and their interaction as fixed effects, and patient as random effect.Ethics and disseminationThis trial was approved by the Regional Committee of Medical and Health Research Ethics, REC no. 2018/1809. The main results will be published in international peer-reviewed open access scientific journals and to policy-makers and end users in relevant channels.Trial registration numberClincalTrials.gov Identifier:NCT03859063, registered on 1 March 2019.