Grigoriou 2021.

Study characteristics
Methods	Study design Cross‐over RCT Study dates Duration of follow‐up: 9 months Time frame: not reported
Participants	Study characteristics Country: Greece Setting: not reported Inclusion criteria: 18 to 70 years, HD patients both sexes who received regular HD treatment for at least 6 months; adequate dialysis delivery with Kt/V > 1.1; good compliance with dialysis treatment; serum albumin > 2.5 g/dL, Hb ≥ 11g/dL, sleep onset latency > 15 minutes or sleep efficiency < 85% or arousal index > 25 Exclusion criteria: unable to give informed consent; opportunistic infection in the last 3 months; malignancy or infection requiring IV antibiotics within 2 months prior to enrolment; myo‐skeletal contraindication to exercise requirement for systemic anticoagulation; participating or participated in an investigational drug or medical device study within 30 days or five half‐lives, pregnant, breastfeeding or female of childbearing potential who does not agree to remain abstinent or to use an acceptable contraceptive regimen; lactate dehydrogenase > 300U/L, prolonged heart wave (QT) interval (as defined by corrected QT (QTc) > 460 msec in males and > 470 msec in females) on screening ECG, known current alcohol or drug abuse, known or suspected hypersensitivity to the study medication or any of its ingredients Number (analysed/randomised): overall (21/22) Mean age ± SD (years): overall (56 ± 19) Sex (M/F): overall (17/4) Dialysis type: HD Mean dialysis vintage ± SD (years): intervention group (10.6 ± 8.26); control group (11.0 ± 7.74) Comorbidities CVD: not reported Diabetes: not reported Hypertension: not reported Depression: not reported
Interventions	Intervention classificationn Non‐pharmacological intervention Indication: study targeting fatigue Intervention group Intradialytic exercise training program Control group Not participate in any type of systematic exercise training, standard HD Co‐interventions The patients underwent HD therapy 3 times/week using high flux polysulfone dialysers. The HD session lasted approximately 4 hours. An enoxaparin dose of 40 to 60 mg was administered IV before the beginning of each HD session. EPO therapy was given after the completion of HD session to normalize Hb within 12 to 14 g/dL
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available Fatigue Physical Fatigue will be assessed by hand grip, functional tests, cardiorespiratory max test: after 9 months Mental Fatigue will be assessed by questionnaires: after 9 months Cognitive Fatigue will be assessed by questionnaires: after 9 months Body composition: after 9 months Muscle functionality: after 9 months QoL aspects (assessed by questionnaires): after 9 months Sleep quality and quantity (assessed by questionnaires and a full night polysomnography): after 9 months Cardiac functionality: after 9 months Neurological Assessment: after 9 months
Notes	Additional information Funding: University of Thessaly, Ministry of Development and Larissa University Hospital Conflicts of interest/disclosures: none Trial registration identification number: NCT01721551 A priori published protocol was reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The order of the two scenarios was randomly applied in all patients using a computer random number generator." Comment: A computer random number generator is considered as low risk of bias
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not reported. However, interventions were different and participants and/or investigators could be aware of the treatment assigned
Blinding of outcome assessment (detection bias) All outcomes	High risk	It was not clear if outcomes were assessed with an appropriate measure, without differences between groups. However, subjective measures were used, it was not stated whether outcomes were assessed without knowledge of treatment allocation, and knowledge of treatment assignment may have influenced reporting. Participant beliefs about the superiority/inferiority of either intervention could have influenced their assessment of the outcome, but there was no evidence that this was likely. Fatigue was not clearly reported. However, other subjective outcome were reported
Incomplete outcome data (attrition bias) All outcomes	High risk	Overall 21/22 participants completed the study. No information were reported to assess differences between groups
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan was reported. Fatigue was not clearly assessed and data were not reported in a format that was extractable for meta‐analysis (cross‐over study). All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	Unclear risk	Baseline characteristics were not clearly reported. Funding was unlikely to influence the data analysis