HCV HIV
Conditions
Keywords
Community Based Research, Hepatitis C Virus and Human Immunodeficiency Virus, Ledipasvir/Sofosbuvir, Fixed Dose Combination, Sustained Viral Response
Brief summary
Background: \- Treatment for Hepatitis C has changed a lot in the past 2 years. Most of this change comes from a combination of medicines that is yielding high cure rates. But its long-term effects are uncertain. One problem is that a lot of people need the treatment, but only a few specialists can give it. The success rate for Hepatitis C treatment by primary care doctors, nurse practitioners, or physician assistants is largely unknown. Researchers want to see how provider type affects treatment outcomes. They will conduct a large, community-based study in the District of Columbia. Objectives: \- To see if people can be treated for Hepatitis C safely and successfully in community-based health centers. Eligibility: \- Adults who need treatment for chronic Hepatitis C infection. Design: * Participants will be screened with blood tests. Their current medicines will be reviewed. * Participants will give researchers access to their medical records. Researchers will follow participants through these records. * Participants will see a primary care or infectious disease provider. The provider will tell them about their treatment. They will be told how often they will visit the provider and how often they will have their blood drawn. They will get a calendar of study visits. * Participants will take Harvoni for 8, 12, or 24 weeks. They will visit their care provider monthly. * Participants will have monthly follow-up visits for up to 3 months after they finish their medicine. * Participants will have yearly follow-up visits with their care provider for up to 10 years.
Detailed description
Treatment for hepatitis C has been revolutionized in the last 2 years with the advent of combination antiviral therapy yielding high cure rates; although, the long term effects of treatment remain uncertain. Use of these medications has been limited to clinical trial settings typically by highly specialized care teams in tertiary care hospitals. As the prevalence of hepatitis C is significant, there exists a significant imbalance between patients who require treatment and specialists who provide treatment. Success rates in treatment of hepatitis C by primary care doctors or physician extenders, such as nurse practitioners or physician assistants, is largely unknown. As such, we propose the first community-based, large scale, longitudinal study of directly acting antiviral (DAA)-based treatment for chronic hepatitis C, set in the District of Columbia. Within this study, approximately 600 HCV genotype 1 monoinfected and HCV/HIV coinfected subjects will be treated with ledipasvir/sofosbuvir (90 mg/400 mg) fixed dosed combination for 8-24 weeks, based on the medication labeling instructions, and followed for both immediate (SVR12) and long term (comorbid disease, cirrhosis, hepatocellular carcinoma, transplantation and mortality) outcomes over a 10 year study period. The study will be conducted exclusively in the District of Columbia clinics associated with the NIH DC Partnership for AIDS/HIV Progress (DC PFAP), which serves a population comprised primarily of minorities, with a high degree of negative predictors of treatment response. In this study, participants will be assigned to treatment either by (1) an ID or hepatology specialist, (2) primary care provider, or (3) physician extender. Please see Figure 1 study schema for an approximate distribution of subjects. Each of these provider groups will undergo uniform training on treatment of hepatitis C and management of adverse events prior to initiation of study. All subjects will sign informed consent and agree to treatment and follow up phases of the study. During the course of the study, subjcts will be clinically evaluated based on American Association for the Study of Liver Diseases (AASLD)/ the Infectious Diseases Society of America (IDSA) guidelines for the management of hepatitis C. Clinical data from subjects will be captured in a city wide cohort database, which will store guideline-driven data points from each clinic visit within the network. Through this trial we will explore the efficacy of managing hepatitis C subjects with directly acting antiviral therapy in an urban, community-based setting, and investigate the effect of provider type (specialist, primary care, or physician extender) on treatment outcome. We will detail the safety and tolerability of this treatment. We will assess variability in treatment outcomes between monoinfected and HIV-coinfected subjects. Finally, we will evaluate the public health impact of large-scale treatment of HCV infected subjects in preventing long-term clinical outcomes. As the first interferon (IFN)- and ribavirin (RBV)-free, urban community-based treatment utilizing new standard of care criteria, this study will serve as a model for implementation of similar practice patterns globally.
Interventions
DRUGLedipasvir 90 mg and Sofosbuvir 400 mg
Ledipasvir 90 mg and Sofosbuvir 400 mg fixed dose combination as per standard of care treatment guidelines
Sponsors
National Institutes of Health Clinical Center (CC)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Male or female at least 18 years of age at time of screening who is determined to be eligible based on evaluation by a treating provider, 2. Documentation of genotype 1 (GT-1) infection, liver fibrosis staging by any AASLD/IDSA guideline approved measurement, and HIV status determination. 3. Chronic HCV genotype-1 infection prior to study enrollment. Chronic HCV-infection is defined as the following: positive for anti-HCV Ab or HCV RNA at least 6 months before screening, and positive for HCV RNA and anti-HCV Ab at the time of screening 4. Compensated liver disease, both with and without cirrhosis, as determined clinically by referring provider 5. If coinfected with HIV, stable HIV disease as determined by a treating provider 6. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements, and must voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
Exclusion criteria
1. Women who are pregnant or breastfeeding 2. Screening laboratory analyses showing any of the following abnormal laboratory results: \- Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min as estimated by the Modification of Diet in Renal Disease (MDRD) equation (utilized by LabCorp): eGFR = 175 times SerumCr(-1.154) age(-0.203 1.212 (if patient is black) 0.742 (if female) 3. Diagnosis of hepatocellular carcinoma as defined by pre-screening medical history 4. Any other conditions in the opinion of the investigator that would interfere with the compliance or endpoints of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Achieve Sustained Viral Response (SVR12) 12 Weeks After the Stop of Treatment Drugs | At least 12 weeks after completion of medication | The primary outcome was the number of patients with sustained viral response measured 12 weeks after the stop of treatment. The viral response was assessed by serum HCV RNA concentrations lower than the limit of quantification (\<15IU/mL). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Standard of care treatment using ledipasvir 90mg-sofosbuvir 400mg by mouth daily for 2, 3, or 6 months | 600 |
| Total | 600 |
Baseline characteristics
| Characteristic | Standard of Care |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 78 Participants |
| Age, Categorical Between 18 and 65 years | 522 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 589 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 578 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 184 Participants |
| Sex: Female, Male Male | 416 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 600 |
| other Total, other adverse events | 76 / 600 |
| serious Total, serious adverse events | 0 / 600 |
Outcome results
Primary
Number of Subjects Who Achieve Sustained Viral Response (SVR12) 12 Weeks After the Stop of Treatment Drugs
The primary outcome was the number of patients with sustained viral response measured 12 weeks after the stop of treatment. The viral response was assessed by serum HCV RNA concentrations lower than the limit of quantification (\<15IU/mL).
Time frame: At least 12 weeks after completion of medication
Population: The analyses included all patients who received at least one dose of ledipasvir-sofosbuvir
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care | Number of Subjects Who Achieve Sustained Viral Response (SVR12) 12 Weeks After the Stop of Treatment Drugs | 516 Participants |