AIMTo assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection.METHODSPatients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined.RESULTSIn total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSIONDUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.
As a result of the path route and the width change and in order to connect south of K4 + 726.852 bridge with road in HengZhou avenue smoothly, we need to reverse the cross slope which takes up 2 percent of the bridge deck. We analyze three different reform plans, so as to ensure security of HengZhou bridge. Firstly, we compare the influences for the bridge structure bearing capacity from different projects. Secondly, we study the transformed force performance. Thirdly, we evaluate the bearing capacity. Result shows that transformation surfacing method is costless and easy to operate. The bearing capacity meet the requirements after the transformation. The research achievement has some reference value to other similar bridge for strengthening
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