Sugiyama 2021.

Study characteristics
Methods	Study characteristics Study design: parallel RCT Study duration: December 2018 to June 2020 Study follow‐up: 6 months
Participants	Baseline characteristics Country: Japan Setting: multicentre (21 sites) Inclusion criteria: > 20 years; ESKD undergoing HD; diagnosed with dialysis‐associated secondary carnitine deficiency and had been administered IV L‐carnitine at a dose of 1000 mg/HD session 3 times weekly for at least 3 months Randomised number (intervention group 1/intervention group 2 /control): 19/18/20 Dialysis modality: HD Mean age ± SD (years): intervention group 1 (64.5 ± 13.3); intervention group 2 (69.4 ± 12.7); control group (69.5 ± 9.8) Sex (M/F): intervention group 1 (13/6); intervention group 2 (12/6); control group (10/7) Dialysis duration: not reported Exclusion criteria: unstable lower limb cramps and general fatigue; Hb < 10 g/dL; deemed to have inadequate information by a physician
Interventions	Intervention group 1 L‐carnitine (IV): 1000 mg 3 times/week at each dialysis session for 12 months Intervention group 2 L‐carnitine (IV): 1000 mg once/week at dialysis session for 12 months Placebo: saline twice/week Control group Placebo: saline 3 times/week
Outcomes	Outcomes relevant to this review Anaemia‐related markers: Hb Myocardial function: LVM, ejection fraction Death (any cause)
Notes	Funding source: a Grant‐in‐Aid for Welfare and Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. One of the authors has received honoraria, including lecture fees, from Otsuka Pharmaceutical Co., Ltd
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "using simple randomization procedures (computer‐generated list of random numbers) by the clinical research coordinator"
Allocation concealment (selection bias)	Low risk	Quote: "using simple randomization procedures (computer‐generated list of random numbers) by the clinical research coordinator"
Blinding of participants and personnel (performance bias)	High risk	Quote: "single‐blind, placebo‐controlled, randomized clinical"
Blinding of outcome assessment (detection bias) Anaemia‐related markers	Low risk	The outcome measurement is not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) Myocardial function	Unclear risk	Insufficient information to permit judgement
Blinding of outcome assessment (detection bias) Death	Low risk	The outcome measurement is not likely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) Anaemia‐related markers	Low risk	Missing outcome data balanced in numbers across intervention groups
Incomplete outcome data (attrition bias) Myocardial function	Low risk	Missing outcome data balanced in numbers across intervention groups
Incomplete outcome data (attrition bias) Death	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Pre‐specified outcomes of interest to this review were reported
Other bias	High risk	Funding source: a Grant‐in‐Aid for Welfare and Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. One of the authors has received honoraria, including lecture fees, from Otsuka Pharmaceutical Co., Ltd