A prospective, multicenter, post-marketing observational study to measure the quality of life of HCV genotype 1 infected, treatment naïve patients suffering from fatigue and receiving 3D regimen: The HEMATITE study

Abstract

Aim: Fatigue is the most commonly reported symptom of Hepatitis C Virus (HCV) infected patients and severely impacts their quality of life. The aim of this study was to measure the impact of 3D regimen treatment on the fatigue, daytime physical activity and sleep efficiency of HCV infected patients with fatigue.

Methods: HEMATITE was an observational, prospective, open-label, single-arm, Swiss multi-centric study in mono-infected HCV genotype 1 patients. The 28 week observation period comprised of 4 weeks preparation, 12 weeks treatment and 12 weeks follow-up. Fatigue was assessed using the fatigue severity scale (FSS) questionnaire. Patients with FSS ≥ 4 (clinically significant fatigue) were included. The activity tracker, ActiGraph GT9X Link®, was used to measure daytime physical activity and sleep efficiency. Outcome analysis was performed on a scaled down intention to treat (sdITT) population, which excluded patients with insufficient tracker data at all study visits and a modified ITT (mITT) population, which consisted of patients with complete tracker data at all study visits.

Results: Forty of 41 patients in the ITT population had a sustained virologic response 12 weeks post-treatment (SVR12). Mean baseline FSS score was 6.0 for the sdITT population and 5.9 for the mITT population and decreased from baseline to 12 weeks post-treatment by 2.6 (95% confidence interval [CI]: 2.1, 3.1) for the sdITT (n = 37) population and 2.8 (95% CI: 2.2, 3.4) for the mITT (n = 24) population. Mean daytime physical activity or sleep efficiency did not change considerably over the course of the study.

Conclusion: Measurement by the activity tracker of mean day time physical activity did not show a considerable change from baseline to SVR12 upon treatment with 3D regimen. Nevertheless, a reduction of fatigue as assessed with the validated fatigue severity scale (FSS) was observed, suggesting a causative role of HCV in this extrahepatic manifestation.

Trial registration: ClinicalTrials.gov identifier: NCT03002818.

Conflict of interest statement

Nasser Semmo has received research grants, consulting fees and/or speaker fees from AbbVie and Gilead and consulting fees from MSD. Beat Müllhaupt has received speaking and/or consulting fees from Merck/MSD, AbbVie, Intercept, Astra, Bayer, BMS, Gilead and research support from Gilead. Lorenzo Magenta has received research grants, consulting fees and/or speaker fees from AbbVie, Gilead, Janssen, BMS and MSD. Olivier Clerc has received consulting fees from AbbVie. David Semela has received research grants, consulting fees and/or speaker fees from AbbVie, Bayer, BMS, Gilead, Intercept and MSD. Ralph Torgler and Lisa Ruckstuhl are employees of AbbVie and own stock/options of AbbVie. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow chart of study participants.

ITT = intention to treat population; sdITT = scaled down ITT population; mITT = modified ITT population.

Fig 2

Change in mean daytime physical activity from baseline (Day 1) to Day 28, Day 84 and 12 weeks post-treatment (Day 168) is shown for (a) the sdITT population and (b) the mITT population. ° = outlier (value maximum 1.5 to 3 fold box length); * = extreme value (> 3 fold box length); mITT = modified intention to treat; sdITT = scaled down intention to treat; V = study visit.

Fig 3

Distribution of mean FSS score at screening (Day -28), baseline (Day 1), Day 28, Day 84 and 12 weeks post-treatment (Day 168) is shown for (a) the sdITT population, (b) the mITT population and (c) all patients that had a completed FSS questionnaire for all study visits (n = 39). The decrease in mean FSS score from baseline (Day 1) to Day 28, Day 84 and 12 weeks post-treatment (Day 168) is shown for (d) the sdITT population and (e) the mITT population. ° = outlier (value maximum 1.5 to 3 fold box length); FSS = fatigue severity scale, mITT = modified intention to treat; sdITT = scaled down intention to treat; V = study visit.