Terg 2002.

Methods	RCT Placebo‐controlled Cross‐over design
Participants	Pruritus: CP Description: participants with cholestasis Number of participants randomised: 20 Group A (naltrexone‐placebo): 11 Group B (placebo‐naltrexone): 9 Number of participants evaluable: 18 Withdrawals/dropouts: 2 Reason for dropout: 1 because of clinical impairment due to progression of prior hepatocarcinoma, 1 because of nausea and vomiting Age: (mean ± SD) Group A: 55 ± 10, range 36‐70 years Group B: 55 ± 9, range 42‐69 years Sex (male/female): Group A:3/8 Group B: 0/9 Underlying disease(s): PBC (n = 15), chronic hepatitis C (n = 2), PSC (n = 1), overlap syndrome (n = 1), cryptogenic cirrhosis (n = 1) Participant pool: 2 centres Setting: inpatient Haemodialysis: NA Baseline pruritus assessment: yes Duration/severity of pruritus: lasting 6 to 11 months; no information on severity Baseline parameter: Pruritus score (VAS 10 cm): (mean ± SD) Group A: 6.27 ± 1.61 (daytime), 6.52 ± 2.42 (night‐time) Group B: 6.32 ± 3.12 (daytime), 5.03 ± 2.48 (night‐time)
Interventions	Intervention 1: naltrexone (25 mg/d) 2x (9:00 h and 14:00 h) Intervention 2: placebo (25 mg/d) 2x (9:00 h and 14:00 h) Additional medication: All participants were instructed to continue with their previous medication throughout the study. Route of administration: oral Duration of treatment: 2 weeks (2 weeks naltrexone/placebo ‐ 1 week washout ‐ 2 weeks cross‐over) Follow‐up: no information
Outcomes	Pruritus assessment: VAS 10 cm Adverse events Additional outcomes: serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, prothrombin time, serum albumin, platelets, red and white cell count, serum urea, creatinine, sodium, potassium, γ‐glutamyltransferase
Notes	Additional open trial: 2 additional months naltrexone for participants with at least 50% pruritus decrease (9 participants included)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was generated by tables with two random numbers for each patient. These were the numbers of the bottles containing medication or placebo"
Allocation concealment (selection bias)	Low risk	"Information was placed in sealed, opaque, and numbered envelopes."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"This study was 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	No missing outcome data; no information on intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	No indication
Size of study (possible biases confounded by small size)	High risk	Number of participants randomised: 20
Other bias	Low risk	Assessment of pruritus by counting the pills remaining in the box