Lo 2012.

Methods	Open, parallel‐arm, single‐centre randomised clinical trial evaluating secondary prevention
Participants	121 participants with cirrhosis and previous variceal bleeding. Proportion of men: carvedilol 11.9%; nadolol 20% Mean age: carvedilol 53.0 years; nadolol 49.8 years Proportion for primary prevention: carvedilol 0%; nadolol 0% Proportion with: alcohol‐related cirrhosis: carvedilol 36.0%; nadolol 43.0% hepatitis B‐related cirrhosis: carvedilol 21.0%; nadolol 32.0% hepatitis C‐related cirrhosis: carvedilol 31.0%; nadolol 15.0% large varices: carvedilol 93.0%; nadolol 88.0% carvedilol: grade 2 84.2%; grade 3 15.8% nadolol: grade 2 77.4%; grade 3 12.2% ascites: carvedilol 39%; nadolol 42%
Interventions	Intervention comparison: carvedilol vs nadolol Initial dose of carvedilol: 6.25 mg once daily, increased to 6.25 mg twice daily if systolic blood pressure > 100 mmHg. Dose tapered if systolic blood pressure < 90 mmHg; mean 10.4 mg ± standard deviation 2.2 mg (range 6.25‐12.5 mg) Initial dose of nadolol: 20 mg once daily, titrated to achieve a 25% reduction in heart rate, or 55 beats per minute; mean 45 mg ± standard 13 mg (range 20‐80 mg) Co‐intervention: participants in the control group also received isosorbide mononitrate Treatment duration: the trial was terminated 6 months after enrolment of the last participant.
Outcomes	Outcomes included in meta‐analysis: mortality, variceal bleeding, and adverse events after a median duration of 30 months (21 days‐4 years)
Country of origin	Taiwan
Publication status	Full‐paper
Inclusion period	March 2005‐July 2009
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Table of random numbers
Allocation concealment (selection bias)	Low risk	Serially numbered, opaque, sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open trial without blinding or participants or personnel
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open trial without blinding of outcome assessment except endoscopists determining site of variceal bleed
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 participant in each group was lost to follow‐up; 4 participants in the carvedilol group and 5 participants in the nadolol group did not comply with the trial protocol. All participants accounted for; intention to treat analyses employed using last observed response carried forward
Selective reporting (reporting bias)	Low risk	All clinically relevant outcome measures are reported. We did not have accesses to the trial protocol.
For‐profit funding	High risk	Carvedilol supplied by Roche, Italy; nadolol supplied by E.R. SQUIBB SONS, Taiwan
Other bias	Low risk	No other biases identified
Overall bias assessment (mortality)	High risk	High risk of bias
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of bias