Semeniuk 2000.

Study characteristics
Methods	Study design Cross‐over RCT Study dates Duration of follow‐up: 12 weeks (first period) Time frame: November 1997 to June 1998
Participants	Study characteristics Setting: single‐centre Country: Canada Inclusion criteria: ≥ 18 years undergoing HD; had been on dialysis for a minimum of 1 year, had at least 2 of the following symptoms: intradialytic hypotension, muscle cramping, lack of energy, muscle weakness or myopathy, cardiomyopathy, or lack of responsiveness to EPO Exclusion criteria: mentally incompetent to complete a QoL questionnaire Baseline characteristics Number (analysed/randomised): overall (10/16) Mean age ± SD (years): overall (66.9 ± 15.9) Sex (M/F): overall (5/11) Dialysis type: HD Dialysis vintage (years) (mean ± SD): not reported Comorbidities CVD: not reported Diabetes: not reported Hypertension: not reported Depression (clinician diagnosis): not reported
Interventions	Intervention classification Pharmacological intervention Indication: study targeting fatigue Intervention group IV L‐carnitine 20 mg/kg Control group Placebo (normal saline) Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data not available Changes in health‐related quality of life KDQ (Appendix 3): baseline, 6 and 12 weeks Fatigue KDQ (Appendix 3): baseline, 6 and 12 weeks Adverse events (including intradialytic hypertension and cramping) BP Death Nutritional intake: baseline, 6 and 12 weeks Adequacy of dialysis: baseline, 6 and 12 weeks Laboratory parameters: baseline, 6 and 12 weeks Urea Creatinine Iron Hb Albumin
Notes	Additional information Funding: Sigma Tau Conflicts of interest/disclosures: not reported Trial registration identification number: not applicable A priori published protocol: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomised using a table of random numbers."
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: "Double‐blind." Comment: Although 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	Fatigue was assessed with an appropriate measure, without differences between groups. However, 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. However, objective and subjective outcomes were assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	Not reported in sufficient detail at the end of the first phase to perform adjudication
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan were not reported. It was not reported if fatigue was assessed using multiple eligible outcome measurements (scales and time points) were pre‐specified for the first period of the study. 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 clearly reported). All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	High risk	Baseline characteristics between groups were not reported. Funding (pharmaceutical company) could influence the data analysis and interpretation