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. 2023 Jul 19;2023(7):CD011585. doi: 10.1002/14651858.CD011585.pub2

Sidhu 2016.

Study characteristics
Methods Randomised, open‐label, non‐inferiority clinical trial
Participants This trial assessed the effects of rifaximin versus lactulose in 112 people with cirrhosis and minimal hepatic encephalopathy.
There were 57 participants in the rifaximin group and 55 in the lactitol group.
Age (median (range)) years
  • Rifaximin 52 (40 to 65)

  • Lactulose 55 (32 to 65)


Proportion of men (n: %)
  • Rifaximin 39/55 (71)

  • Lactulose 45/57 (79)


Aetiology of cirrhosis (n: %)
Rifaximin
  • Alcohol 34 (60)

  • Alcohol and hepatitis B virus (0)

  • Alcohol and hepatitis C virus 5 (9)

  • Autoimmune hepatitis 1 (2)

  • Hepatitis B virus 2 (4)

  • Hepatitis C virus 57 (9)

  • Non‐alcoholic fatty liver disease 8 (14)

  • Cryptogenic 2 (4)


Lactulose
  • Alcohol 24 (44)

  • Alcohol and hepatitis B virus 1 (2)

  • Alcohol and hepatitis C virus 6 (11)

  • Autoimmune hepatitis 0 (0)

  • Hepatitis B virus 1 (2)

  • Hepatitis C virus 12(22)

  • Non‐alcoholic fatty liver disease 5 (9)

  • Cryptogenic 6 (11)

Interventions Intervention: rifaximin 400 mg thrice daily
Control intervention: lactulose 30 to 120 ml daily
Dosage adjusted to ensure passage of 2 to 3 semi‐formed stools daily
Co‐intervention: none
Duration of treatment: 90 days
Duration of follow‐up: 9 months after inclusion
Outcomes Neuropsychiatric assessment
Battery of 5 psychometric tests: number connection, figure connection, digit symbol, picture completion, block design. Participants were diagnosed as having minimal hepatic encephalopathy if two or more of the psychometric tests were abnormal.
Inclusion period March 2011 to August 2013
Outcomes included in meta‐analyses Mortality, reversal of minimal hepatic encephalopathy, development of overt hepatic encephalopathy, adverse events, health‐related quality of life (Sickness Impact Profile)
Country of origin Single centre in India
Notes Publication status: full paper
Vested interests bias: none
Additional information: published initially as abstract. Additional information on randomisation methods, blinding and mortality was obtained from the corresponding author in May 2014. Published as full paper article in 2015, with a follow‐up in 2017. Further information on randomisation methods, blinding of statistician, adverse events, and whether data were collected for ammonia levels and length of hospital stay. We also clarified other identified references to include from this study group. This information was obtained from the corresponding author on 18 April 2021.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "...randomised in to two groups (group A and B) using computer‐generated randomisation (1:1)." p. 2. Information from authors confirms this: "Patients were randomised using computer‐generated randomisation 1:1." This was done by the lead statistician, who was blinded at that point.
Judgement: probably done
Allocation concealment (selection bias) Low risk Quote: "..concealed by using sealed envelopes.." p. 2. Information from corresponding author confirms this: "Sequentially numbered, sealed, opaque envelopes were used for treatment allocation by a coordinator who was not an investigator." Judgement: probably done
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk This study is reported is the published paper as unblinded: "Another limitation was that our study was unblinded." We did however receive Information from the corresponding author to the effect that: "Investigators, data entry operator and statistician (up to the point of analysis) were blinded regarding treatment drugs"
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk See above. Further information from the author: "The statistician was not strictly blinded during analysis. However, he preferred to be genuinely concerned about the blinding in this study."
Incomplete outcome data (attrition bias)
All outcomes Low risk Withdrawals and dropouts reported in information from the corresponding author, and on p. 3‐4 in paper
Selective reporting (reporting bias) Low risk Published as a full report
Other bias Low risk No other bias detected
Overall bias assessment (mortality) Low risk Low risk in all domains except detection bias
Overall bias assessment (non‐mortality outcomes) High risk High risk of detection bias