Maddrey 1978

Methods	Randomised, double‐blind clinical trial with parallel‐group design (3 groups) Country: USA Analyses were not performed according to the intention‐to‐treat principle. Sample size calculation was not reported.
Participants	Demographic characteristics Age: (mean + SD): 40 + 8.5 in the treatment group and 42.3 + 11.1 in the control group Sex: 12 men (50%) in the treatment group and 23 men (74%) in the control group Inclusion criteria and degree of severity People with a history of long‐standing and recent alcoholism were referred to the Liver Service (The Johns Hopkins Hospital). A percutaneous liver biopsy was performed unless precluded by coagulation abnormalities. Alcoholic hepatitis was defined histologically as an inflammatory hepatic disease with cell swelling and hydropic change, cell necrosis, and polymorphonuclear leukocytic infiltration. Exclusion criteria People with active gastro‐intestinal haemorrhage, pancreatitis, history of peptic ulcer, active infection, presence of hepatitis B infection, or history of previous viral hepatitis were excluded. Maddrey's discriminant‐function. All people had wedged hepatic venous pressure determination. Randomisation procedure "Patients were randomized for treatment within three groups based on apparent severity of disease. Random drug sequences were arranged within each group." Number of participants randomised n = 57 "Patients were randomised for treatment within three groups based on apparent severity of disease. Group A (moderately ill), serum bilirubin > 3 mg per dL; hepatomegaly; and clotting factors adequate to allow liver biopsy Group B (more severely ill), hyperbilirubinaemia and hepatomegaly as in A with additional presence of ascites and/or hepatic encephalopathy, but coagulation studies adequate for liver biopsy Group C (severely ill), hyperbilirubinaemia and hepatomegaly as in A and B, with or without ascites and/or hepatic encephalopathy, but coagulation abnormalities precluded liver biopsy." Prednisolone group: n = 25 Control group: n = 32
Interventions	Experimental group: Dose: 40 mg/d orally (eight tablets 5 mg each every morning) Control group: identical placebo tablets Additional interventions to the trial groups: all trial participants were offered a 3000 calorie diet. Protein (1 g to 1.5 g per kg) was provided for people with no evidence of hepatic encephalopathy. In people with encephalopathy, protein restriction to 20 g/d or less and lactulose therapy. Ascites was managed with sodium restriction alone or with the addition of spironolactone in those who did not respond with diuresis in 5 days. All participants initially received 100 mg of thiamine intramuscularly. B‐complex multivitamins and folic acid U mg) were given each day Duration of treatment: from 28 to 32 days Follow‐up: until discharge
Outcomes	The trial outcomes were"factors important in determining outcome in alcoholic hepatitis and to evaluate further the effects of corticosteroid therapy on early mortality and on the progression to cirrhosis, as reflected by histological changes and wedged hepatic venous pressure." Reported outcomes in the trial Early mortality Complications of therapy Liver function and hematological tests Wedged hepatic venous pressure Factors associated with a fatal outcome Discriminant function analysis
Notes	This study was supported by Research Grant AA00201 from the National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health, and by Grant RR‐35 from the Clinical Research Centers Program, United States Public Health Service. Prednisolone and placebo tablets were provided by the Division of Steroid Research, The Upjohn Company, Kalamazoo, Mich. Letter sent to authors in March 2000. No answer received. No further attempts were made.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were randomised for treatment within three groups based on apparent severity of disease. Random drug sequences were arranged within each group"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Prednisolone (5 mg) or identical placebo tablets were given in a single dose of 8 pills each morning for 28 to 32 days. (Prednisolone (5 mg) and identical placebo tablets were provided by the Division of Steroid Research, The Upjohn Company, Kalamazoo, Mich.). The investigators were not aware of which regimen the patient was receiving until the completion of the study."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	3.5% dropped out or were withdrawn, i.e. "Two additional patients were removed from the study after randomisation. One patient who was randomised to the placebo group bled from oesophageal varices before receiving the study drug. He subsequently stopped bleeding and survived. Another patient had an episode of upper gastrointestinal haemorrhage presumably from oesophageal varices after receiving prednisolone for 9 days and the drug was stopped." 1/25 prednisolone group and 1/32 placebo group
Selective reporting (reporting bias)	Low risk	All‐cause mortality, serious adverse events, and liver‐related mortality were reported.
For‐profit bias	Unclear risk	Prednisolone and placebo tablets were provided by the Division of Steroid Research, The Upjohn Company, Kalamazoo, Mich. However, no further details were provided.
Other bias	Low risk	None suspected