Results

Recruitment and retention

Patient flow, including recruitment to and retention in the trial, is detailed in Figure 1. The trial recruited prevalent patients with stage 5 CKD receiving HD therapy from June 2015 to June 2019 in five regional kidney units in the UK. In total, the trial recruited 379 participants. A total of 335 participants attended a baseline study visit: 175 participants who were randomised to the exercise intervention and 160 participants who were randomised to usual care. Participants were informed of group allocation only after completing all baseline assessments. Fifty-nine patients allocated to the exercise intervention and 60 participants allocated to usual care did not complete the 6-month assessment. In total, seven participants died during the study: three participants from the intervention group and four participants from the usual-care group. In the intervention group, 40 participants were withdrawn and 16 did not attend for the final 6-month assessment. In the usual-care group, 15 participants were withdrawn and 14 participants did not attend the 6-month assessment. Participants were more likely to withdraw from the trial if they were older and female. Analysis to establish how participants who withdrew differed from those who remained in the trial, stratified by arm, did not reveal significant differences in age, sex or weight, but it does appear that participants were more likely to drop out of the exercise arm if they had a history of heart failure and cerebrovascular disease (Table 1). The primary outcome was therefore known for 243 (73%) participants who attended a baseline visit: 116 (66%) participants in the intervention group and 127 (79%) participants in the usual-care group (see Figure 1).

FIGURE 1 The PEDAL trial Consolidated Standards of Reporting Trials (CONSORT) diagram. Reproduced with permission from Greenwood et al.1 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure. (Figure not reproduced here; see the original article.)

Demographic and other baseline characteristics

Baseline characteristics of randomised participants

Of the 335 randomised participants, 62.4% were male (see Table 1). The median age was 59.3 years [interquartile range (IQR) 48.8–70.5 years]. Half of the randomised population was white and 34.3% was black African/black Caribbean. The mean weight was 80.5 kg (SD 20.1 kg) and most participants were classified as overweight or obese [median BMI of 27.8 kg/m² (IQR 24.0–32.2 kg/m²)]. A total of 13% reported a musculoskeletal or orthopaedic condition, and participants had haemoglobin levels of 100–120 g/l at baseline.

Prior cardiovascular events and risk factors

A history of major adverse cardiovascular events affected the minority of participants; prior stroke and myocardial infarction were present in 8% and 12% of the cohort, respectively. A history of heart failure or peripheral vascular disease was recorded for 4% and 10% of participants, respectively. At baseline, 78% of participants had hypertension, 39% had diabetes, 21% had hyperlipidaemia and 58% had never smoked.

Adherence

A total of 175 participants received the exercise intervention. A median of 47% (IQR 28–77%) of exercise training sessions were completed by participants in the intervention group at 6 months. A total of 23% of participants had dropped out of the exercise intervention at 6 months, and 58% of participants reported temporary cessation of the intervention. At 6 months, only 18% of participants were adhering to the full exercise prescription (Table 2).

Outcomes

The results for the primary and secondary outcome measures are presented in Tables 3 and 4. The mean difference in the change in PCS score from baseline to 6 months between the intervention group and control group was 2.4 AUs (95% CI –0.1 to 4.8 AUs; p = 0.055). In the whole sample, despite no statistical improvement in PCS score (p = 0.055), it is noteworthy that the absolute mean difference in change in PCS score from baseline to 6 months between the intervention group and control group was 2.4 AUs (95% CI –0.1 to 4.8 AUs).

Safety and harms

The number of hospitalisations, all-cause mortality and cardiovascular mortality were not different between the groups. Although these results should be interpreted cautiously owing to the lack of events for these secondary outcomes, there was no obvious increase in SAEs in the intervention group either (Tables 5 and 6).

Subgroup analyses

In patients who completed > 30% of their prescribed exercise sessions, the difference in the change in PCS score was ≈ 3 AUs and statistically significant (p = 0.039). The relationship between compliance (as percentage of sessions completed) and PCS score was not significant [estimated change in PCS score per 10% difference in compliance, 0.6 AUs (95% CI –0.1 to 1.3 AUs); p = 0.11] (Table 7). The relationship between compliance (as percentage of sessions completed) and VO_2 peak was weak but statistically significant [estimated change in VO_2 peak per 10% difference in compliance, 0.3 ml/kg/minute (95% CI 0.0 to 0.6 ml/kg/minute); p = 0.047] (Table 8).