D'Amico 2002.

Study characteristics
Methods	Randomised clinical trial
Participants	Country: Italy Period of recruitment: 1992–1996 Number randomised: 57 Postrandomisation dropouts: 0 (0.0%) Revised sample size: 57 Mean age (years): 56 Females: 27 (47.4%) Small varices: 0 (0.0%) High risk of bleeding: 57 (100.0%) Other features of decompensation: 9 (15.8%) Alcohol‐related cirrhosis: not stated Viral‐related cirrhosis: 49 (86.0%) Autoimmune disease‐related cirrhosis: not stated Other causes of cirrhosis: not stated Other exclusion criteria: large varices known for > 1 year; hepatocellular carcinoma; serum creatinine > 2 mg/dL; aged > 75 years; features of decompensation such as hepatic encephalopathy; contraindications to beta‐blockers
Interventions	Group 1: beta‐blockers + nitrates (n = 30) Further details: nadolol 20 mg daily increased by 20 mg until maximum tolerated dose (heart rate > 55 bpm) was reached + isosorbide mononitrate 10 mg twice daily increased to 40 mg twice daily until maximum tolerated dose (systolic blood pressure > 90 mmHg) was reached Group 2: beta‐blockers (n = 27) Further details: nadolol 20 mg daily increased by 20 mg until maximum tolerated dose (heart rate > 55 bpm) was reached + placebo
Outcomes	Mortality at maximal follow‐up, any adverse events (number of participants), variceal bleed at maximal follow‐up (any) (number of participants), other features of decompensation at maximal follow‐up Follow‐up (months): 31
Notes	Source of funding (quote): "The trial drug and placebo were kindly provided by Chiesi Farmaceutici, Florence, Italy" Trial name/trial registry number: not stated Attempted to contact the authors in February 2020; received no additional information
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Treatment packages were consecutively numbered and contained active treatment or placebo according to a randomisation by permuted blocks of 10…Each patient in the included trial was assigned to the next treatment package (which randomly contained the active drug or placebo)." Comment: although details on sequence generation were not reported, the method of allocation concealment used makes it highly likely that the sequence was random.
Allocation concealment (selection bias)	Low risk	Quote: "Treatment packages were consecutively numbered and contained active treatment or placebo according to a randomisation by permuted blocks of 10…Each patient in the included trial was assigned to the next treatment package (which randomly contained the active drug or placebo)." Comment: although the precise method of sequence generation was not reported, the allocation was probably concealed to implement this method of blinding.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Double‐blind placebo controlled trial." Comment: blinding was achieved using a placebo.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Double‐blind placebo controlled trial." Comment: blinding was achieved using a placebo.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no postrandomisation dropouts
Selective reporting (reporting bias)	Low risk	Comment: a prepublished protocol was not available, but the authors reported mortality, adverse events, and variceal bleed adequately.
Other bias	Low risk	Comment: no other bias noted