https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61036-9.pdf

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study

BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.

Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)60538-9.pdf

Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial

https://www.natap.org/2015/HCV/PIIS01688278150062.pdf

The importance of resistance to direct antiviral drugs in HCV infection in clinical practice.

Lancet Seminar – Hepatitis C

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)60494-3.pdf

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial

Background . The pandemic coronavirus infection has contributed to the development of effective preventive methods to slow the spread of the virus. Mass vaccination is the only way to protect oneself from infection. The development of drugs, including vaccines, involves clinical trials (CT). The problem of conducting a CT is recruiting the necessary number of volunteers. Goal : to identify specifics of motivation of patients participating in the clinical trial of COVID-19 vaccines, as it is a very important medical and sociological issue requiring more detailed study. Materials and Methods . The results of an anonymous questionnaire survey of volunteers participating in the “EpiVacCorona” vaccine CT are presented. Overall, 203 questionnaires were analyzed, containing 19 questions answered by the residents of Kaliningrad, aged 20 to 84 years. At the stage of completion of participation in the clinical trial, information was obtained about the respondent’s attitudes to the trial, the main factors of motivation or demotivation to participate, the degree of their trust in the trial. Results . Information disseminated through the employer was an effective way to organize patient recruitment for the vaccine CT; the effectiveness of using the media was quite low. The positives of participation in the CT for volunteers were ethical considerations. Negatives for participants were the risks associated with adverse reactions or receiving a placebo. Relatives had the greatest influence on the volunteers’ decision to participate in the CT, and medical professionals, media personalities, and scientists had less influence. Conclusion . The results will help to improve patient recruitment, patient awareness of the CT, and the benefits to medicine and society. Motivating and demotivating factors will improve patient recruitment. 

/pdf/specifics-of-motivation-of-volunteers-participating-in-in-a-20eykrif.pdf

Vladimir V Rafalsky

Papers

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial

Specifics of motivation of volunteers participating in in a clinical trial of the COVID-19 vaccine

Clinical Pharmacology