Background <p>Kidney cachexia is a debilitating and under-recognised complication of advanced chronic kidney disease (CKD), characterised by unintentional weight loss, muscle wasting, inflammation, and reduced functional capacity. Its profound impact on morbidity, quality of life, and healthcare utilisation underscores the need for targeted, implementable interventions. The multicomponent implementation strategy for a multi-modal, integrated, exercise, anti-inflammatory, and dietary advice (MMIEAD) intervention seeks to address this gap. Guided by the practical, robust implementation, and sustainability model (PRISM), which incorporates reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) outcomes, this study aims to ensure strong intervention–context alignment to support future scalability.</p> Methods <p>The MMIEAD model will be evaluated by determining patient eligibility and recruitment rates, identifying intervention retention and adherence, assessing key statistical and methodological considerations to inform optimal study design and data collection burden, conducting a qualitative process evaluation to examine intervention acceptability and practicality, and determining the feasibility of undertaking a definitive economic evaluation.</p> Design <p>This mixed-methods study consists of three phases. Phase 1 will deliver and evaluate a 12-week multimodal intervention using a feasibility cluster randomised controlled trial (cRCT) design. Phase 2 will undertake a qualitative process evaluation with healthcare practitioners (HCPs) and patients. Phase 3 will assess the feasibility of conducting a full economic evaluation.</p> Participants <p>Patients will be eligible if they have haemodialysis-dependent CKD stage 5 for more than 3 months, have experienced unintentional weight loss of at least 5% in the previous 12 months, or have a body mass index &lt;20 kg/m², and are aged over 18 years. HCPs will be eligible if they are members of the multidisciplinary healthcare team for more than 3 months and have had exposure to the study.</p> Setting and randomisation <p>The study will be conducted across four outpatient haemodialysis units in the UK. Two sites have been randomly allocated to the intervention group and two to the control group.</p> Sample <p>For phases 1 and 3, a total of 40 patient participants will be recruited (10 per intervention site and 10 per control site). For phase 2, qualitative data will be collected through interviews with approximately 15 patients and interviews or focus groups with 15 HCPs across all sites. Recruitment commenced on 08.09.25 following ethical approval (REC reference: 25/NI/0069).</p> Discussion <p>Using multi-method analyses informed by PRISM/RE-AIM dimensions, we will generate evidence on the feasibility, acceptability, and contextual fit of the MMIEAD intervention to prepare for a definitive UK-wide multi-site cRCT.</p> Trial registration <p>Trial registration number NCT07107087 (30 July 2025). <a href="https://clinicaltrials.gov/study/NCT07107087">https://clinicaltrials.gov/study/NCT07107087</a></p>