Results Summary
What was the research about?
The hepatitis C virus, or HCV, can cause long-term infection that can lead to serious liver damage, liver failure, or even death. Several oral medicines can cure HCV. But questions remain about how these medicines compare with each other.
In this study, the research team compared how well two medicine combinations work to cure HCV:
- Ledipasvir/sofosbuvir, or LDV/SOF
- Elbasvir/grazoprevir, or EBR/GZR
The team also looked at patient side effects, HCV-related symptoms, and well-being.
What were the results?
After three months of treatment, a similar percentage of patients in each group:
- Were cured of HCV (97 percent for LDV/SOF and 95 percent for EBR/GZR)
- Experienced side effects such as nausea and headache while taking the medicines (54 percent for LDV/SOF and 57 percent for EBR/GZR)
- Took their medicine as directed (84 percent for LDV/SOF and 80 percent for EBR/GZR)
During treatment, commonly reported side effects, such as headache, nausea, and fatigue, didn't get worse with either combination. Well-being improved for both patient groups during and after treatment.
At nine months after treatment, compared with patients who took EBR/GZR, patients who took LDV/SOF reported greater decreases in HCV-related:
- Nausea and diarrhea
- Pain
- Fatigue and problems with sleeping
- Problems with memory, language, and thinking
However, at 20 months after treatment, patients in the two groups didn't differ in the level of symptom improvement or well-being. Patients in both groups continued to improve in these areas.
Who was in the study?
The study included 1,128 adult patients with HCV. Of these patients, 51 percent were White, 42 percent were Black, and 7 percent were another race. The average age was 55, and 60 percent were men.
What did the research team do?
The research team assigned patients by chance to one of two groups: EBR/GZR or LDV/SOF. In one group, patients took one tablet daily of EBR/GZR for 12 to 16 weeks. They received the medicine free of charge. In the other group, patients’ insurers paid for LDV/SOF. Patients took one tablet daily for 8 to 12 weeks.
To learn if patients were cured of HCV and about side effects, the research team reviewed patients’ health records for 12 weeks during treatment. Patients also completed surveys during treatment and 9 and 20 months after treatment. The survey asked if patients took their medicine as directed and about HCV-related symptoms and well-being.
Patients with HCV, patient organizations, insurers, healthcare providers, health systems, and pharmacists helped design the study.
What were the limits of the study?
Health insurers declined to pay for LDV/SOF for 21 percent of patients assigned to that group. Some of these patients didn’t take part in the study or took EBR/GZR instead, which could have affected the results.
The research team couldn’t test two new HCV medicine combinations because they weren’t available at the time of the study. These medicine combinations are glecaprevir/pibrentasvir and sofosbuvir/velpatasvir.
Future research could compare how well new types of HCV medicines work to cure HCV.
How can people use the results?
Patients with HCV and their doctors can use the results when considering treatments.
| How this project fits under PCORI’s Research Priorities PCORI identified hepatitis C as an important research topic. Patients, clinicians, and others wanted to learn: What approaches work best to diagnose, treat, and manage hepatitis C, especially for people who are at high risk of infection? To help answer this question, PCORI launched an initiative in 2015 on Clinical Management of Hepatitis C Infection. The initiative funded this research project and one other. |
Professional Abstract
Objective
To compare the effectiveness of two oral direct-acting antiviral medication regimens in curing hepatitis C virus (HCV) infection
Study Design
| Design Element | Description |
|---|---|
| Design | Pragmatic randomized controlled trial |
| Population | 1,128 adult patients with compensated liver disease, HCV genotype 1a or 1b, and health insurance |
| Interventions/ Comparators |
|
| Outcomes | Primary: treatment effectiveness (cure rate, defined as sustained virologic response 12 weeks after treatment completion); percentage of patients experiencing the following medication-associated side effects: headache, nausea, and fatigue Secondary: short-term and long-term HCV-associated symptoms post-treatment; adherence to medication; functional well-being |
| Timeframe | 3-month follow-up for primary outcomes |
This pragmatic, multisite randomized controlled trial compared the effectiveness of two treatment regimens, ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR), in curing HCV infection. The study also compared patient side effects and HCV-related symptoms after treatment, medication adherence and persistence, and functional status.
The study included 1,128 adult patients with HCV infection. Of these patients, 51% were White, 42% were Black, and 7% reported another race. The average age was 55, and 60% were male.
Researchers randomized patients to receive either LDV/SOF or EBR/GZR. Patients received EBR/GZR free of charge from researchers, while insurers paid for LDV/SOF for patients assigned to that regimen. Patients who received LDV/SOF took one tablet daily for 8 to 12 weeks. Patients who received EBR/GZR took one tablet daily for 12 to 16 weeks.
Researchers reviewed medical records to look at cure rates 12 weeks after treatment and side effects noted during treatment. Researchers also surveyed patients about their adherence to medication during the study and about improvements in HCV-related symptoms and functional well-being during treatment and 9 and 20 months after treatment.
Patients with HCV, patient organizations, insurers, healthcare providers, health systems, and pharmacists helped design the study.
Results
The medication regimens did not differ significantly in the percentage of patients who:
- Were cured of HCV 12 weeks after treatment (97% for LDV/SOF and 95% for EBR/GZR)
- Experienced side effects from the medications while taking them (54% for LDV/SOF and 57% for EBR/GZR)
- Were nonadherent to medication (16% for LDV/SOF and 20% for EBR/GZR)
During treatment, commonly reported side effects did not worsen with either regimen. Nausea and fatigue improved during treatment with LDV/SOF. Patients reported improved functional well-being during treatment and at nine months after treatment with both regimens, especially patients who received LDV/SOF. At 20 months after treatment, patients reported similar and substantial improvements in both symptoms and functional well-being.
Limitations
Failure to start treatment was more common with patients randomized to LDV/SOF. One reason was that health insurers denied coverage to 21% of patients. Of these denials, 75% were by state Medicaid programs. The resulting imbalance in patient characteristics between study arms may have biased the study results. Another limitation was that researchers could not evaluate two new oral medication combinations (glecaprevir/pibrentasvir and sofosbuvir/velpatasvir) because they were not available at the time of the study.
Conclusions and Relevance
In this study, both medication combinations had similar cure rates for HCV infection and a similar proportion of patients with side effects.
Future Research Needs
Future research could compare the effectiveness of new oral medication combinations in treating HCV infection.
| How this project fits under PCORI’s Research Priorities PCORI identified hepatitis C as an important research topic. Patients, clinicians, and others wanted to learn: What approaches work best to diagnose, treat, and manage hepatitis C, especially for people who are at high risk of infection? To help answer this question, PCORI launched an initiative in 2015 on Clinical Management of Hepatitis C Infection. The initiative funded this research project and one other. |
Final Research Report
View this project's final research report.
Journal Citations
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- Reviewers asked the researchers to provide additional background information on their study participants, particularly related to alcohol use disorder, opioid use disorder, and mental illness. The researchers explained that they did not record substance use disorders based on feedback from their patient engagement group. That group wanted to move away from the stereotype of substance abuse among people with hepatitis C. They also noted that substance use is often inaccurately recorded in patient records. The researchers did add information to the final report about the few occurrences in the study sample of people denied insurance coverage due to a failed drug test.
- The reviewers identified a possible source of selection bias in the study because more participants in one study arm than in another had Medicaid insurance rather than private insurance, which could be considered an indicator of poverty. The researchers acknowledged this concern and explained that they tested for bias through sensitivity analyses that are provided in the report appendices. The sensitivity analyses showed no evidence of bias or other concerns in the main study results.
- One reviewer expressed concern about the timeliness of this study given the rapid changes in the standard of care for people with hepatitis C. The researchers countered that their recent paper in a major hepatology journal indicates the importance of this research. They also expanded their discussion of the most important outcomes and lessons learned in the report.