Plasma samples for PegIFN-��-2a and Rbv Cmin determinations were drawn on the morning of the day scheduled for weekly administration of pegIFN-��-2a after 11.45 to 12.15 hours to the previous Rbv dose (otherwise, blood samples were discarded) at weeks 1, 2, 4, further information and monthly afterwards until the end of therapy. Samples were stored at ?80��C until tested. Plasma pegIFN-��-2a and Rbv concentrations were assayed by enzyme-linked immunosorbent assay Hu-INF-�� (PBL Biomedical Laboratories, Piscataway, NJ), and reverse-phase high-performance liquid chromatography (HPLC-UV) as previously described [14]. All calibration standards, quality control samples, and study samples were analyzed in duplicate. Results are shown as the mean of the duplicates for the study samples.
End-points and assessment of efficacy and safety The primary efficacy end-point was SVR, defined as undetectable serum HCV-RNA at 24 weeks after completion of treatment. Efficacy data were assessed by both intention-to-treat (ITT) and by per-protocol analysis. Secondary end-points were to assess the influence of IL28B polymorphisms on SVR and the relationship between the plasma pegIFN-��-2a and Rbv concentrations and virological responses in patients receiving treatment. Rapid virologic response (RVR) was defined as a plasma HCV-RNA<15 IU/mL at week 4 of treatment. Early virologic response (EVR) was defined as a plasma HCV-RNA<15 IU/mL or a decrease of ��2 log10 IU/ml at week 12 of treatment or earlier, respectively. End of treatment response (ETR) was defined as undetectable serum HCV-RNA at the end of therapy.
Relapses were defined as a detectable serum HCV-RNA at any time point after attaining ETR. Safety was assessed by means of AEs reported by patients or detected by investigators, and laboratory results at scheduled visits on weeks 1, 2, 4, 8, 12, and monthly thereafter until the end of therapy, and categorized via a standardized toxicity grade scale (AIDS Clinical Trials Group). For toxicity and response investigations, analysis dropouts were considered until the last available visit. Drug treatment Patients started treatment with the combination of weekly 135 ��g pegIFN-��-2a plus oral Rbv (400 mg twice daily), and a planned duration of 20 weeks after attaining undetectable serum RNA-HCV. Treatment was discontinued at week 12 in patients not achieving EVR, and these cases were considered as virological failures.
Antiretroviral treatment and use of erythropoietin remained at the responsible physicians’ judgment. Anacetrapib Statistical analysis This pilot study was designed as a single-arm, uncontrolled trial, with a historical comparison. For ��a priori�� sample size calculations, the Apricot trial, the largest clinical trial with pegIFN-��-2a plus Rbv conducted in HCV/HIV-coinfected patients (3,21) so far, was considered as historical reference. The SVR rate observed in patients harbouring HCV genotype 2 or 3 in the Apricot trial was 62%.
No related posts.