RESUMO
BACKGROUND: Hepatic encephalopathy (HE) is one of the most important severe complications of liver cirrhosis. Thought to be caused by elevated blood levels of gut-derived neurotoxins (particularly ammonia) entering the brain, HE manifests as a wide range of neurological or psychiatric abnormalities, which increase the risk of mortality, result in substantial morbidity and negatively affect the quality of life (QoL) of both patients and their caregivers. HE is also associated with a substantial economic burden. Rifaximin-α 550 mg is a locally acting oral antibiotic that reduces the effects of ammonia-producing intestinal flora, and which is used to help reduce the recurrence of overt HE. The efficacy of rifaximin-α 550 mg was established in a randomised controlled trial and long-term extension study. However, 'real-world' evidence is also required to assess how this efficacy may translate into effectiveness in clinical practice, including the potential impact of treatment on healthcare resource utilisation. METHODS: The Prospective Real-world Outcomes Study of HE Patients' Experience on Rifaximin-α 550 mg (PROSPER) is a multinational, multicentre, observational study that will be conducted under real-world clinical practice conditions. Comprising a retrospective phase (up to 12 months) and a prospective phase (up to 24 months), and employing a robust statistical methodology, PROSPER has been specifically designed to minimise the bias associated with observational studies. The primary endpoint will be the effect of rifaximin-α 550 mg treatment on HE- and liver-related hospitalisation rate and duration of hospitalisation. Secondary endpoints will include comprehensive assessments of the impact of treatment on the QoL and workplace productivity of patients and caregivers, a global assessment of treatment effectiveness and safety/tolerability. Approximately 550 patients will be enrolled. CONCLUSIONS: PROSPER will provide valuable real-world information on the effectiveness of rifaximin-α 550 mg in reducing the recurrence of HE, and its impact on the QoL and work productivity of patients and their caregivers. By providing data on both the direct costs (e.g., hospitalisation rate, duration of hospitalisation) and indirect costs (such as work productivity) of HE, PROSPER should help confirm whether rifaximin-α 550 mg treatment represents a good use of economic resources. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02488993.
RESUMO
BACKGROUND AND AIMS: NER1006 is the first 32 fluid ounce (1 L) polyethylene glycol-based bowel preparation. This randomized, multicenter, colonoscopist/central reader-blinded phase 3 non-inferiority trial assessed the efficacy, safety, and tolerability of NER1006 versus trisulfate for bowel cleansing. METHODS: Patients undergoing colonoscopy were randomized (1:1) to receive NER1006 or trisulfate, using evening/morning split-dosing administration. Blinded central readers used the validated Harefield Cleansing Scale to evaluate 2 alternative primary endpoints: overall bowel-cleansing success and high-quality cleansing of the ascending colon/cecum. Secondary endpoints included lesion detection, Boston Bowel Preparation Scale (BBPS) assessment, and adherence. The non-inferiority margin was 10% and the significance threshold was P < .025. RESULTS: Of 621 patients randomized (NER1006, n=310; trisulfate, n=311), 556 were evaluated for efficacy (NER1006, n=276; trisulfate, n=280). NER1006 achieved non-inferiority versus trisulfate for both primary endpoints of overall bowel-cleansing success (85.1% vs 85.0%; difference, 0.14%; one-sided 97.5% lower confidence limit [LCL], -8.15%; P = .528) and high-quality cleansing of the ascending colon/cecum (35.9% versus 29.3%; difference, 6.58%; LCL, -1.69%; P = .059). BBPS assessments supported overall bowel-cleansing success rates. Lesion detection rates were similar between the groups. The percentage of patients with treatment-related adverse events was 14.9% with NER1006 and 9.4% with trisulfate. Both bowel preparations showed similar overall tolerability and safety profiles. Adherence was very high in both arms. CONCLUSIONS: With evening/morning split dosing, NER1006 was as effective as trisulfate for overall bowel and right-sided colon cleansing. Adverse event rates were slightly higher with NER1006 than trisulfate, but did not compromise tolerability, adherence, or efficacy. (Clinical trial registration number: NCT02254486.).