Lindor 2009.

Methods	Study design: a long‐term, randomised, double‐blind controlled trial.
Participants	Country: United States of America. Publication language: English. Inclusion criteria: ‐ chronic cholestatic disease of at least 6 months duration; ‐ serum alkaline phosphatase at least 1½ times the upper limits of normal; ‐ retrograde, operative, percutaneous, or magnetic resonance cholangiography demonstrating intrahepatic and/or extrahepatic biliary duct obstruction, beading or narrowing consistent with PSC within 1 year of the study entry; ‐ liver biopsy in the previous 1 year that was available for review and compatible with the diagnosis of PSC. Exclusion criteria: ‐ coexistent conditions such as preexisting advanced malignancies or severe cardiopulmonary disease that would limit their life expectancy to less than 2 years; ‐ inability to provide consent; ‐ treatment with UDCA, pentoxifylline, corticosteroids, cyclosporine, colchicine, azathioprine, methotrexate, D‐penicillamine, budesonide, nicotine, pirfenidone, or tacrolimus in the 3 months prior to study entry; ‐ inflammatory bowel disease patients requiring specific treatment in the preceding 3 months except for maintenance therapy with 5‐ASA compound; ‐ anticipated need for liver transplantation within 2 years (expected survival of <80% at 2 years based on Mayo risk score); ‐ recurrent variceal bleeding, spontaneous uncontrolled encephalopathy, INR >1.5 uncorrected by vitamin K, or resistant ascites that suggested an anticipated survival of less than 1 year; ‐ pregnancy or lactation; ‐ age less than 18 years or greater than 75 years; ‐ findings highly suggestive of liver disease of other etiology ‐ previous intraductal stones or operations on the biliary tree, other than cholecystectomy ‐ recurrent ascending cholangitis requiring hospitalisation occurring more than two times per year. Participants: ‐ UDCA group (n = 76): Mean age (years): 47.9 (range 20.5 to 75.6); Ratio of sex (M/F): 38/38; Duration of disease (years): 1.3 (range 0.1 to 13.4); Concurrent IBD no. : 55 (72%). ‐ Placebo group (n = 74): Mean age (years): 45.3 (range 17.9 to 73.6); Ratio of sex (M/F): 48/26; Duration of disease (years): 1.0 (range 0.0 to 49.5); Concurrent IBD no. : 61 (%).
Interventions	UDCA group: ‐ Dose: 28 to 30 mg/kg body weight/day in divided doses given with meals and a bedtime snack. ‐ Route: orally. ‐ Duration: five years. Placebo group: ‐ identical placebo.
Outcomes	Primary outcome measures: Death or transplantation; Development of cirrhosis, varices, cholangiocarcinoma.
Notes	Letter was sent to the authors in August 2010. A reply with no additional information was received shortly after.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer‐generated sequence.
Allocation concealment?	Unclear risk	The method for allocation not described.
Blinding? All outcomes	Low risk	Identical‐appearing placebo.
Incomplete outcome data addressed?	Low risk	Number and reasons for patients withdrawal from study were reported.
Free of selective reporting?	Low risk	Study outcomes clearly pre‐specified and data reported.
Sample size calculation	Low risk	Stated and used.
Intention‐to‐treat analysis	Low risk	Stated and used.