Fatouros 2010.

Study characteristics
Methods	Study design Cross‐over RCT Study dates Duration of follow‐up: 8 weeks Time frame: not reported
Participants	Study characteristics Setting: single centre Country: Greece Inclusion criteria: chronic therapy for at least 1 year before the study; 4‐hours HD sessions 3 times/week (mean Kt/V at least 1.4) with standard bicarbonate dialysis using biocompatible membranes (low‐flux polysulfone); Hb levels at least 11 g/dL (ESAs were administered to all patients); absence of antioxidant supplementation (vitamin E, statins, or any medication for the reduction of uric acid); adequate nourishment (total serum protein 6.8 ± 0.5 g/dL and serum albumin 4.3 ± 0.2 g/dL; no residual renal function; ability to perform stationary cycling; had not received any L‐carnitine treatment in the previous 6 months Exclusion criteria: the presence of any active infectious/inflammatory disease (serum CRP levels at least 0.5 ± 0.4 mg/dL); uncontrolled hypertension and DM; diseases that might interfere with exercise capacity and/or be exacerbated by activity such as Ischaemic cardiopathy or symptoms related to coronary artery disease, anaemia (Hb levels < 11 g/dL, HCT < 33%), chronic lung disease, and orthopaedic disorders; use of steroids, immunosuppressives, and psychotropic agents; hospitalisation within 3 months before the study Baseline characteristics Number (analysed/randomised): intervention group (not reported/6); control group (not reported/6) Mean age ± SD (years): overall (53.8 ± 2.3) Sex (M/F): intervention group (6/0); control group (6/0) Dialysis type: HD Mean dialysis vintage ± SD (years): overall (7.08 ± 0.24) Comorbidities CVD: not reported Diabetes: not reported Hypertension: not reported Depression (clinician diagnosis): not reported
Interventions	Intervention classification Pharmacological intervention Indication: study reported fatigue (reported as time to fatigue) Intervention group L‐Carnitine (IV): 20 mg/kgof dry body weight Control group Placebo: saline of an equal dose Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available VO2peak, 12‐lead ECG, perceived exertion, respiratory quotient, heart rate, time to exhaustion, brachial artery cuff pressure, exercise time to exhaustion: assessed before and after the first phase Heart rate: assessed before and after the first phase Blood samples (blood carnitine, lactate, malondialdehyde, protein carbonyls, reduced and oxidized glutathione, antioxidant capacity, catalase, glutathione peroxidase activity, uric acid): assessed before and after the first phase Fatigue (time to fatigue): time frame not clearly stated Nutrition evaluation (5‐day diet recalls): assessed before and after the first phase Anthropometric profile (body weight, body mass index, percentage body fat): assessed before and after the first phase
Notes	Additional classification Funding: Democritus University Medical School. The funding sources played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. The authors state that the results of the present study do not constitute endorsement by the American College of Sports Medicine Conflicts of interest/disclosures: none Trial registration identification number: not reported A priori published protocol: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Sequence generation methods were not reported in sufficient detail to permit judgement
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	Unclear risk	Quote: "Twelve haemodialysis patients received either L‐carnitine (20 mg/kg‐1 IV) or placebo in a double‐blind, placebo‐controlled, counterbalanced, and cross‐over design for 8 weeks." Comment: Although the author reported that the study used a double‐blind design, information about blinding of participants and investigators were not clearly stated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "In their second visit, subjects returned their diet recall forms and underwent a progressive diagnostic test to exhaustion (GXT) on a stationary cycle ergometer to evaluate their peak oxygen consumption (VO2 peak) while blood was collected before and immediately after testing." Comment: The outcomes were assessed with an appropriate measure, without differences between groups. However, objective and subjective outcomes were assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	Attrition was not reported in sufficient detail to permit judgment in the first phase of the study
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan was not reported. It was not reported if multiple eligible outcome measurements (scales and time points) were pre‐specified. It was unclear if the reported approach to analysing this outcome was pre‐specified or influenced by the results. Fatigue at the end of treatment was not reported in a format that was extractable for meta‐analysis (cross‐over study: data related to the first period were not reported). All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	Unclear risk	No data were available to assess the possible imbalance between groups. Funding was unlikely to influence the data analysis and authors had no conflicts of interest