P0958THE EX-FRAIL CKD TRIAL: A PILOT RANDOMISED CONTROLLED TRIAL OF A HOME-BASED EXERCISE PROGRAMME FOR PRE-FRAIL AND FRAIL, OLDER ADULTS WITH CHRONIC KIDNEY DISEASE
Authors: Nixon Andrew , Bampouras Theodoros , Gooch Helen , Young Hannah , Finlayson Kenneth , Pendleton Neil , Mitra Sandip , Brady Mark , Dhaygude Ajay 
Published: June 2020

Abstract

Background and Aims
Frailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes. However, exercise training may improve physical function leading to associated improvements in outcomes. The EX-FRAIL CKD trial (ISRCTN87708989) aimed to inform the design of a randomised controlled trial (RCT) that investigates the efficacy of a progressive home-based exercise programme in pre-frail and frail older adults with CKD.

Methods
Patients aged ≥65 years with CKD G3b-5 and a Clinical Frailty Scale score ≥4 were eligible for participation. Participants categorised as pre-frail or frail, following Frailty Phenotype (FP) assessment, were randomised to receive a tailored 12-week home-based exercise programme or usual care (UC). Primary outcome measures included recruitment, intervention adherence, outcome measure completion and participant attrition rate. Secondary outcome measures included frailty status (FP), physical function (walking speed, handgrip strength and Short Physical Performance Battery [SPPB]), fall concern (Falls Efficacy Scale-International tool [FESI]), symptom-burden (Palliative Care Outcome Scale-Symptoms RENAL [POS-S RENAL]) and health-related quality of life (Short Form-12v2 [SF-12]). Outcome measures are reported descriptively with 95% confidence intervals (CI) as recommended for pilot trials. Progression criteria to RCT stage were defined as: (1) eligibility: STOP &lt;5%, GO &gt;10%; (2) recruitment: STOP &lt;10%, GO &gt;30%; (3) exercise adherence: STOP: &lt;30%, GO &gt;70%; (4) outcome measure completion: STOP &lt;70%, GO &gt;80%; and (5) loss to follow-up: STOP &gt;50%, GO &lt;25%.

Results
Six hundred and sixty-five participants had an eligibility assessment with 201 (30% [95% CI 27-34]) patients eligible for enrolment. Thirty-five (17% [95% CI 12-23]) participants were recruited. Six participants were categorised as robust and therefore withdrawn prior to randomisation. Fifteen participants were randomised to exercise (mean age 77.0±8.3 years; mean eGFR 18.9±7.0 ml/min/1.73m2) and 14 to UC (mean age 78.8±7.0 years; mean eGFR 20.4±7.2 ml/min/1.73m2). Eleven (73% [95% CI 45-92]) exercise group participants completed an average of ≥2 exercise sessions/week. Eight (28% [95% CI 13-47]) participants were lost to follow-up. Retained participants (n=21, 100% [95% CI 84-100]) completed all outcome measures. There were 32 adverse events in the exercise group and 22 in the UC group. Within the exercise group, there were 2 hospitalisations (considered unrelated to exercise) and 12 adverse reactions: musculoskeletal pain (9), fall (1), nocturnal leg cramps (1) and postural dizziness (1). The odds ratio for improvement in frailty status with exercise was 5.50 (95% CI 0.46-65.16) and odds ratio for deterioration in frailty status was 0.63 (95% CI 0.05-8.20). The adjusted mean group difference in walking speed, grip strength and SPPB between exercise and UC groups were: 0.01 metres/second (95% CI -0.07-0.10), 3.6 kg (95% CI -0.6-7.9) and 0.5 (95% CI -0.9-1.8), respectively. The adjusted mean group difference in POS-S RENAL, FESI, SF-12 Physical Component Summary and SF-12 Mental Component Summary scores were: -1.4 (95% CI -6.6-3.7), 3.4 (95% CI -3.5-10.3), -3.9 (95% CI -9.3-1.5) and 0.2 (95% CI -6.2-6.6), respectively.

Conclusion
Eligibility, adherence and outcome measure progression criteria thresholds were exceeded; however, recruitment and loss to follow-up progression criteria thresholds were not achieved. Analysis of a nested qualitative study will explore perceived barriers to participation and retention. The EX-FRAIL CKD trial demonstrates that it is possible to progress to a definitive RCT with adaptations that address the barriers described. It has also provided preliminary evidence that frailty status and physical function may be improved with a home-based exercise programme in patients living with frailty and CKD.