Home-based exercise for people living with frailty and chronic kidney disease: a mixed-methods pilot randomised controlled trial

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 <5%, GO >10%; (2)
recruitment: STOP <10%, GO >30%; (3) exercise adherence:
STOP: <30%, GO >70%; (4) outcome measure completion: STOP
<70%, GO >80%; and (5) loss to follow-up: STOP >50%,
GO <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Six participants were categorised as robust and therefore withdrawn prior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.