The baseline characteristics of both groups were almost comp
The baseline characteristics of both groups were almost comparable (Table 1.).
The vRVR rates and the SVR12 rates calculated per each intention-to-treat (ITT) population and for those who completed the full protocol (PP) in each group are presented in (Table 2).
The vRVR rates showed no statistically significant difference between groups (49/60 (81.67% (95% confidence interval (CI): 70.08–89.44%) in the fixed 12weeks group, versus 48/60 (80% (CI: 68.22–88.17%) in the response-tailored group; p=0.817)).
Fifty eight out of the total 60 (ITT) patients in the reference group (fixed 12weeks) achieved SVR12 (96.67% (CI: 88.64–99%)). Whereas, 59 out of the total 60 (ITT) patients in the test group (tailored duration) achieved SVR12 (98.33% (CI: 91.14–99.71%)).
One out of the 48 patients who achieved vRVR in the test group (tailored duration) dropped-out during the study; all the remaining 47 patients (100% (CI: 92.4–100%)) who completed their full 8weeks treatment protocol (PP analysis) finally achieved sustained virologic response at 12weeks post-treatment (SVR12/8w). Therefore, the SVR12/8w rate in the total subset eligible for 8weeks (ITT) analysis was 97.92% (CI: 89.1–99.6%).
The differences between the 2 groups in the vRVR rates and in SVR12 rates (both ITT and PP) were not statistically significant by confidence interval and the z test for proportion (Table 2).
Non-inferiority was confirmed since the upper bound of the two-sided 95% confidence interval (CI) for the absolute difference in proportions of SVR12 between groups (P(reference)−P(test)) did not exceed the specified non-inferiority margin of +0.1 (10%), both in the intention to treat (ITT) population (−1.67%, CI: −9.8%–+5.9%), and in the per-protocol (PP) population (−1.69%, CI:−9%–+4.58%). (Fig. 2).
All treatment-emergent-adverse-events with causality category possible or above were included in the intention-to-treat safety analysis. No fatalities or serious adverse events were reported during the gsk3 inhibitor of the study. Similar rates of non-serious, adverse events were reported in both groups. There was no statistically significant difference by z test for proportions but a non-significant trend of higher total adverse events rate in the fixed 12weeks group; all were mild in severity (Table 3).
Discussion To our knowledge, this is the first study to address the evaluation of a shortened duration of 8weeks for a dual sofosbuvir plus daclatasvir therapy based on an on-treatment qualifier. The SVR12 rate in the group of patients that were randomly assigned to treatment duration tailored according to achievement of vRVR was non-inferior to that of the fixed 12weeks duration which is the duration recommended in guidelines so far. The European Association for the Study of the Liver (EASL) latest 2016 Guidelines on treatment of hepatitis C, allowed for shortening the course of treatment for genotype 1 infected patients with Sofosbuvir/Ledipasvir combination to 8weeks in treatment-naive patients without cirrhosis if their baseline HCV RNA level is below 6 million IU/ml (EASL, 2017). This recommendation was based on a post-hoc analysis of ION-3 clinical study results which demonstrated that 8weeks of treatment yielded an SVR12 rate (sustained virologic response rate measured at 12weeks after end of treatment) of 97% (119/123) in treatment-naïve patients without cirrhosis when baseline serum virus load was <6millionIU/ml (Kowdley et al., 2014; Curry et al., 2016). In this study, 100% of those who had achieved vRVR and completed the full protocol finally achieved SVR12. Because all investigators belong to the same medical school that values the role of psychological and spiritual support as factors affecting the immune system; all patients in both groups were treated the same with full psychological and spiritual support throughout the study visits with assurance, explanation and positive suggestions. In addition to this, perceiving the result of treatment with negative or very marked drop in the virus load as early as only 2weeks of therapy, in our experience, may have a positive impact on our patients\' spirits, immune responses, compliance and final results.