Ramond 1992

Methods	A randomised, double‐blind trial Intention to‐treat analysis "The study was approved by the hospital ethics committees"
Participants	Demographic characteristics: 124 alcoholic patients were admitted to 2 centres. Mean age + SD: 48.1 + 1.3; 48.2 + 1.6 Sex: (male): prednisolone group/placebo group 10/9 Randomisation procedure: "... a random code was prepared by computer for each participating center. There was a different code for men and women in each center, so that within each group of six patients (male or female), three patients received prednisolone and three patients placebo. Random sequence of drug or placebo were prepared by the pharmacists at each hospital" Inclusion criteria and degree of severity: "all the patients had biopsy proven alcoholic hepatitis (characterised by hyaline necrosis and infiltration of polymorphonuclear leucocytes) and spontaneous hepatic encephalopathy or a discriminant‐function value higher than 32 (or both)." "Eight patients died before inclusion in the trial." Exclusion criteria "gastrointestinal bleeding or bacterial infection were excluded from the trial unless they could be effectively treated within 48 hours" Presence of hepatitis B surface antigen, presence of HIV antibodies, refusal of liver biopsy, non‐alcoholic hepatitis at histology Number of participants randomised: n = 65 "65 patients were randomly assigned, but 4 were excluded‐ one patient assigned to receive prednisolone was found to have anguilluliasis and her treatment was stopped one day after her inclusion in the study. Three patients assigned to placebo were found not to have satisfied the inclusion criteria . These 4 patients were alive at the end of treatment" Prednisolone group: n = 33 (analysed 32) Placebo group: n = 32 (analysed 29)
Interventions	Prednisolone group: "prednisolone (Solupred) in 20 mg tablets and identical placebo were provided by the pharmacists at each hospital" Dose: "prednisolone 40 mg (40 mg of prednisolone equivalent to 32 mg of methylprednisolone) was given in a single dose of two pills each morning for 28 days", if the participant was unable to take oral medication, "received intravenous infusions of prednisolone (Hydrocortancyl) or placebo prepared by the pharmacists and administered by the pharmacist and administered by the attending physician." Placebo group: "identical placebo was given in a single dose of two pills" Additional treatment: "All patients were provided with 3,000 Kcal containing one gram protein/kg. Patients with hepatic encephalopathy received lactulose therapy. Ascites was managed with sodium restriction or by the spironolactone to the treatment regimen" "B complex multivitamins, folic acid, and antiacids were given each day" Duration of treatment: 28 days Duration of follow‐up: 8 weeks
Outcomes	The trial outcomes were: Mortality Liver biochemistry Liver histology Adverse events
Notes	Country: France. From March 1987‐June 1990 Letter sent to study authors in March 2000. No answer received The trial was stopped at the first interim analysis conducted after inclusion of 61 participants out of the planned 130 participants. The authors used an alpha error below 0.025. This is too high a value to prevent early stopping at a random high. "Drug therapy was interrupted by the attending physician if there was severe bacterial infection or gastrointestinal bleeding, or if a corticosteroid‐related complication was suspected... in patients with such complications the remaining tablets of the study drug were replaced with placebo tablets provided by the pharmacist (the only person who knew which regimen the patient had received first). The principal investigator and their associates were not aware of randomisation procedure or of the medication that the patients were receiving throughout the trial." "65 patients were randomly assigned, but 4 were excluded ‐ one patient assigned to receive prednisolone was found to have anguilluliasis and her treatment was stopped one day after her inclusion in the study. Three patients assigned to placebo were found not to have satisfied the inclusion criteria. These 4 patients were alive at the end of treatment."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"a random code was prepared by computer for each participating centre... There was a different code prepared for men and women in each center, so that within each group of six patients (male and female), three patients received prednisolone and three received placebo"
Allocation concealment (selection bias)	Low risk	"a random code was prepared by computer for each participating centre. Random sequences of drug or placebo were prepared by the pharmacist at each hospital"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"a random code was prepared by computer for each participating centre. Random sequences of drug or placebo were prepared by the pharmacist at each hospital" "prednisolone (Solupred) in 20 mg tablets and identical placebo were provided by the pharmacists at each hospital"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information was provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	1.5% 1 woman left the hospital and then "she was re hospitalised 56 days after enrolment and left again the following day. She was the only patient lost to follow up" 1/33 prednisolone group 0/32 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 tablets and placebo were provided by Laboratoire Houdé (Paris)
Other bias	Low risk	Not suspected