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  • Benny Miles posted an update 5 months, 1 week ago

    Combined virologic response (CVR) comprised both SVR12 and pTVR. Patient management required that HCV RNA was quantified locally. Assays differed by clinical center; some assayed HCV RNA by polymerase chain reaction (PCR) assays with limit of detection (LOD) of 50 IU/mL, whereas others used branched-chain DNA (b-DNA) assays with LOD of 615 IU/mL. Serum samples were also stored for subsequent HCV RNA measurement by a central laboratory. The latter samples were first NVP-LDE225 analyzed by b-DNA assay, and all samples with undetectable results (<615 IU/mL) were then retested by transcription-mediated amplification (TMA) with LOD of 5 IU/mL. For data analysis, HCV RNA central laboratory results were supplemented with local results when samples were missing or insufficient for central testing. Safety measures included physical examination, AE assessment, and laboratory monitoring. Cytopenias with Hb <8 g/dL, ANC <500/uL, or PLT <20,000/uL required treatment interruption or discontinuation. Serious adverse events (SAEs) included standard World Health Organization criteria and specific events related to cirrhosis or LT. SAEs were evaluated for relationship to antiviral treatment by the site principal investigators. Deaths were reviewed by an oversight committee (G.E., A.L., and N.T.) and the data and safety monitoring board (DSMB) for A2ALL to evaluate relationship, if any, to antiviral treatment. The DSMB reviewed safety data quarterly and met twice per year to review study progress. Efficacy was tested first using intent-to-treat (ITT) analyses and subsequently using per protocol (PP) analyses; safety analyses were conducted Levetiracetam using PP analyses. Descriptive statistics were reported as mean and standard deviation (SD) or percentages, as appropriate. Treatment balance over clinical and laboratory characteristics was tested by Student’s t test for continuous variables and chi-square test for categorical variables. Variables predictive of pTVR were tested by logistic regression; covariates tested included baseline HCV RNA, HCV genotype, graft type, treatment duration, use of growth factors during treatment, and achievement of 80% target dose of Peg-IFN and RBV. Proportions of SAEs in treated and untreated patients were compared using two-sided Fisher’s exact tests; SAE rates were compared using Poisson regression. The time to first HCV RNA negativity was estimated by Kaplan Meier method, with censoring at death, but not at transplant. The distributions of HCV RNA by treatment week were estimated using the reverse Kaplan Meier method to account for data below LOD.17 Sample size was calculated for patients with genotypes 1, 4, 5, or 6 assuming a 2:1 randomization (�� = 0.05) and two-sided testing to detect a difference in pTVR of 30% in treated versus 1% in control patients with 89% power (n = 84 transplanted patients).