Johansen 2006.

Study characteristics
Methods	Study design Parallel RCT Study dates Duration of follow‐up: 12 weeks Time frame: not reported
Participants	Study characteristics Setting: single‐centre (San Francisco General Hospital Medical Care outpatient dialysis unit) Country: USA Inclusion criteria: men and women undergoing maintenance HD 3 times/week; adequate dialysis delivery with Kt/V 1.2 and good compliance with dialysis treatment (i.e. not missing more than 2 dialysis treatments in the month before enrolment) Exclusion criteria: dialysis for < 3 months; reasons to be in a catabolic state (including HIV with opportunistic infection in the past 3 months, malignancy, or infection that required intravenous antibiotics within 2 months before enrolment); unable to give informed consent; active IV drug users; thigh dialysis graft; contraindications to resistance exercise training such as MI within 6 months, active angina, uncompensated congestive heart failure, or orthopaedic or musculoskeletal limitations Baseline characteristics Number (analysed/randomised): intervention group 1 (16/19); intervention group 2 (16/20); control group 1 (17/20); control group 2 (19/20) Mean age ± SD (years): intervention group 1 (55.7 ± 13.4); intervention group 2 (55.5 ± 12.5); control group 1 (56.8 ± 13.8); control group 2(54.4 ± 13.6) Sex (M/F): intervention group 1 (10/9); intervention group 2 (13/7); control group 1 (12/8); control group 2 (14/6) Dialysis type: HD Median dialysis vintage, IQR (years): overall (not reported); intervention group 1 (3.33, 0.25 to 24); intervention group 2 (1.17, 0.33 to 12.67); control group 1 (2.13, 0.25 to 13)); control group 2 (2.75, 0.29 to 9) Comorbidities CVD: not reported Diabetes: intervention group 1 (10/19); intervention group 2 (9/20); control group 1 (8/20); control group 2 (12/20) Hypertension: intervention group 1 (18/19); intervention group 2 (20/20); control group 1 (17/20); control group 2 (18/20) Depression (clinician diagnosis): not reported
Interventions	Intervention classification Pharmacological and non‐pharmacological intervention Indication: study targeting fatigue Intervention group 1 Nandrolone decanoate: 100 mg (0.5 mL) for women and 200 mg (1 mL) for men, 3 times/week Intervention group 2 Nandrolone decanoate: 100 mg for women and 200 mg for men, 3 times/week + lower extremity resistance exercise training Control group 1 Placebo Control group 2 Placebo + lower extremity resistance exercise training Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available Change in body weight: assessed at baseline and 3 months Change in body composition: assessed at baseline and 3 months Change in lean body mass Dual‐energy X‐ray absorptiometry: assessed at baseline and 3 months Change in quadriceps muscle cross‐sectional area Magnetic resonance imaging: assessed at baseline and 3 months Change in knee extensor muscle strength Computerized dynamometer: assessed at baseline and 3 months Physical performance: assessed at baseline and 3 months Gait speed Stairs Sit and stand Self‐reported physical functioning Physical functioning of the SF‐36 (asks individuals to characterize their degree of limitation in performing 10 activities as not limited at all, limited a little, or limited a lot): assessed at baseline and 3 months Human Activity Profile (94 activities and patients are asked to report whether they still do the activity, no longer do the activity, or never did the activity): assessed at baseline and 3 months Physical activity Threedimensional accelerometers: assessed at baseline and 3 months Human Activity Profile Maximum Activity Score Human Activity Profile Adjusted Activity Score Laboratory results (pre‐dialysis SCr): assessed at baseline and 3 months Hip abduction Magnetic resonance imaging: assessed at baseline and 3 months Isokinetic knee extension at 90 degrees/s (Nm) Magnetic resonance imaging (assessed at baseline, 3 months) Isokinetic knee extension at 120 degrees/s (Nm) Magnetic resonance imaging: assessed at baseline and 3 months Hip flexion: assessed at baseline and 3 months MRI: assessed at baseline and 3 months Fatigue and change in fatigue Profile of Mood State: assessed at baseline and 3 months Anger/hostility components Profile of Mood State: assessed at baseline and 3 months HRQoL and change in QoL Physical Functioning SF‐36: assessed at baseline and 3 months Adverse events: assessed until the end of treatment Death: assessed until the end of treatment
Notes	Additional information Funding: grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK‐56182). Study drug and matching placebo were kindly provided by Organon, Inc., Roseland, NJ Conflicts of interest/disclosures: not reported 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)	Low risk	Quote: "Participants were randomly assigned to treatment groups in a 1:1:1:1 manner by the research pharmacist using variable block sizes, which were not known to investigators until the completion of the study." Comment: Sequence generation methods were not reported in sufficient detail to permit judgement. No imbalance between intervention groups was apparent
Allocation concealment (selection bias)	Low risk	Quote: "Nandrolone decanoate and a placebo that was identical in appearance to the active drug were prepared and supplied to the research pharmacy by Organon, Inc. (Roseland, NJ)." Quote: "Participants were randomly assigned to treatment groups in a 1:1:1:1 manner by the research pharmacist using variable block sizes, which were not known to investigators until the completion of the study." Comment: Esternal research pharmacist seemed to ensure allocation concealment. No imbalance between intervention groups was apparent
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Interventions included double‐blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections." 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	The 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. However, objective and subjective outcomes were assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Eighty haemodialysis patients were enrolled in the study, and 79 were randomly assigned. [...] Sixty‐eight patients completed the study. Reasons for non completion are shown in Figure 1. Six participants discontinued study drug (four who were receiving placebo and two who were receiving nandrolone) before the end of the treatment period, only two of whom discontinued all study participation. Therefore, results for the four patients who discontinued study drug but were still available for follow‐up measures are included in analyses. Those who received placebo discontinued because of an itchy reaction at the injection site, a nonspecific feeling that the drug was having adverse effects, abdominal pain and liver function test abnormalities, and discovery of a history of prostate cancer. Those who received nandrolone discontinued because of interference with sexual function (after five doses) and fear of possible adverse effects (after three doses)." Comment: 16/19 participants in the intervention group 1 (nandrolone), 16/20 participants in the intervention group 2 (nandrolone + lower extremity resistance exercise training), 17/20 participants in the control group 1 (placebo) and 19/20 participants in the control group 2 (placebo + lower extremity resistance exercise training) completed and reported all measurements of the study (> 5% lost to follow‐up, with differences between groups). Reasons for discontinuations seemed to be related to the treatment allocation.
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan were not reported. Fatigue was reported using multiple eligible outcome measurements (scales, time points). Fatigue at the end of treatment was not reported in a format that was extractable for meta‐analysis. All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	High risk	There was no evidence of different baseline characteristics, or different non‐randomised co‐interventions between groups. Pharmaceutical company who provided the drugs could influenced the data analysis and authors did not report conflicts of interest