Mendenhall 1984

Methods	A co‐operative, multicentre, randomised clinical trial (three intervention groups) Country: USA, 1980‐1983 Intention‐to‐treat analysis Sample size calculation was reported.
Participants	Demographic characteristics Age: (mean 90) prednisolone group 51.5 + 8.2; (mean 88) placebo group 50.4 + 9.2 Sex: male Inclusion criteria and degree of severity Men hospitalised at 6 Veterans Administration Medical Centers in whom diagnosis of moderate or severe alcoholic hepatitis was based on conventional clinical and laboratory changes of this disease. "Histological confirmation was not required, so that severely ill patients were not excluded." Criteria to classify severity: "the degree of jaundice (bilirubin) and coagulopathy (prothrombin time)" Exclusion criteria "..conditions that contradicted corticosteroid therapy: severe infections, active peptic ulcer disease,or insulin ‐ dependent diabetes mellitus) or if they had taken corticosteroids within the preceding three months" "a positive test for hepatitis B surface antigen; clinical or historical evidence of recent parenteral drug abuse, intractable congestive heart failure, neoplasms that commonly metastasize to the liver or nonalcoholic liver diseases" Randomisation procedure "...One hundred thirty‐two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo...Treatment assignment were made by the Coordinating Center (Hines, Ill.)The random assignment of treatments was balanced within each hospital, as well as according to disease severity." Number of participants randomised 178 (n = prednisolone and placebo) + 85 (n = oxandrolone) Prednisolone group: n = 90 (moderate 46, severe 44) Control group: n = 88 (moderate 45, severe 43)
Interventions	Experimental group: prednisolone Dose: "60 mg per day for four days; 40 mg per day for four days; 30 mg per day for four days; 20 mg per day for four days; 10 mg per day for seven days; 5 mg per day for seven final days" Control group: corresponding placebos Duration of treatment: 30 days When possible, participants were evaluated monthly at outpatient clinics. If alcoholic hepatitis recurred and required re‐hospitalisation, the person was reassigned to the same therapy for 30 days with his permission. Duration of follow‐up after randomisation: 1 year (350 days for prednisolone group )
Outcomes	The trial outcomes were Mortality Liver complications Liver biochemistry Adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Treatment assignment was made by the Coordinating Center (Hines, Ill.). The random assignment of treatments was balanced within each hospital, as well as according to disease severity".
Allocation concealment (selection bias)	Low risk	"Treatment assignment were made by the Coordinating Center (Hines,Ill.)".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Medication was packed into unit dose kits at the Veterans Administration Center Pharmacy(Albuquerque, N.M.). The patient, physician and the local hospital pharmacy had no knowledge of the specific medication in use"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	4.5% "Ten patients withdrew from the study before completing treatment (5 given placebo, 3 prednisolone). However, these patients were included in the outcome assessment" 3/ 90 prednisolone group/ 5/88 control group "324 days...37 patients were lost to follow‐up: 13 given placebo, 11 prednisolone"
Selective reporting (reporting bias)	Low risk	All‐cause mortality, serious adverse events, and liver‐related mortality are reported.
For‐profit bias	Unclear risk	"Matching placebos were prepared for each of these medications by Upjohn Company and G.D. Searle and Company."
Other bias	Low risk	None suspected