Pauli‐Magnus 2000.

Methods	RCT Placebo‐controlled Cross‐over design
Participants	Pruritus: UP          Description: participants with ESRD on haemodialysis HD (n = 18) and peritoneal dialysis (PD) (n = 5) Number of participants randomised: 23 Number of participants evaluable: 16 Withdrawals/dropouts: 7 Reason for dropout: During naltrexone period: major gastrointestinal side effects (n = 3), lower limb amputation (n = 1); During placebo period: major gastrointestinal side effects (n = 1), cerebral ischaemia (n = 1) Period unspecified: renal transplantation (n = 1) Age (range): 20‐85 years Sex (male/female): no information Underlying disease(s): no information Participant pool: multicentre Setting: inpatient Haemodialysis: 3x4‐5h/week, Kt/V>1.2, dialysis Peritoneal dialysis: weekly, Kt/V > 2, Hb > 10 g/L Baseline pruritus assessment: yes Duration/severity of pruritus: duration > 6 months; substantial pruritus: persistent, treatment‐resistant, impairing sleep/daytime activities, Baseline parameters: Pruritus score (measured by VAS 10 cm and Duo detailed score, range 0‐45; higher values = more pruritus): Group A (naltrexone ‐ placebo): VAS 5.5, Duo detailed score 17.7 Group B (placebo ‐ naltrexone): VAS 6.5, Duo detailed score 16.8
Interventions	Intervention 1: naltrexone hydrochloride (50 mg/d single morning dose) Intervention 2: placebo Additional medication: no information Route of administration: oral Duration of treatment: 4 weeks (4 weeks naltrexone/placebo ‐ 1 week washout ‐ 4 weeks cross‐over) Follow‐up: no information
Outcomes	Pruritus assessment: VAS (10 cm) and modified Duo score (comprising severity and distribution of pruritus and sleep disturbance) Adverse events Additional outcomes: plasma haemoglobin concentrations, serum concentrations of creatinine, urea, calcium, phosphate, alkaline phosphatase, bilirubin, transaminase, parathyroid hormone
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study was randomised; method not stated
Allocation concealment (selection bias)	Unclear risk	Not information provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind; unclear who was blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analysis and per protocol analysis performed
Selective reporting (reporting bias)	Low risk	No indication
Size of study (possible biases confounded by small size)	High risk	Number of participants randomised: 23
Other bias	Low risk	Missing participant characteristics; sex and underlying disease not stated; no raw data given Assessment of compliance by collecting drug boxes at the end of each study period and taking blood samples for naltrexone measurement at randomly chosen time