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For example, patients on lactulose at enrollment could begin rifaximin treatment only after an on-study HE event.
Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01).
Among the 59 patients taking rifaximin at entry, there was no difference between treatment arms in patients experiencing an HE event, time to event (Table 2; Fig. 2), or total events.
Patients continued to receive their standard of care treatment, including lactulose, rifaximin, or both, until an on-study HE event, after which the patient was allowed to continue on study and have their background standard of care modified.
There was a highly significant correlation between the odds of a patient experiencing an HE event and that patient's ammonia level assessed either at baseline (P = 0.01) or during the study (TNAUC; P = 0.01).
The total number of HE events was also lower in the GPB arm (35 versus 57 in the placebo arm; p = 0.04; Fig. 3; Table 2), and fewer patients experienced dose interruptions resulting from an HE event in the GPB arm (3 patients with 4 total interruptions versus 15 patients with 27 total interruptions; P < 0.01).
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Prespecified secondary endpoints, including time to first HE event and total HE events, were assessed by country-stratified Cox's proportional hazards and Poisson's regression analysis, respectively.
Prespecified secondary endpoints included time to first HE events and total HE events.
Patients randomized to GPB were also significantly less likely to experience HE event-related interruptions in study drug treatment and tended to experience less-severe HE events.
HE events were in all cases adjudicated by the investigator.
Exploratory and post-hoc analyses included analyses of the treatment effect for HE events WH grade ≥2, the relationship of HE events to blood ammonia, results based on rifaximin use, and HE-related hospitalizations.
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