Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant
NCT ID: NCT02533934
Last Updated: 2021-02-02
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
68 participants
INTERVENTIONAL
2016-08-31
2019-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
LIVE-C-Free: Early and Late Treatment of Hepatitis C With Sofosbuvir/Ledipasvir in Liver Transplant Recipients
NCT02631772
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting
NCT02350569
A Multicenter Treatment Protocol of Daclatasvir (BMS-790052) in Combination With Sofosbuvir for the Treatment of Post-Liver Transplant Subjects With Chronic Hepatitis C
NCT02161939
Open Label Study of the Efficacy and Safety of MBL-HCV1 in Combination With Oral Direct-Acting Antivirals in Patients Undergoing Liver Transplantation for Hepatitis C
NCT01532908
Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant
NCT02010255
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In addition, participants in the retrospective arm will be contacted to consent to one prospective study visit for liver staging to determine rates of reversal of decompensation, reversal of cirrhosis and improvements in graft survival post treatment, and for future contact by the NIH Clinical Center to assess longer term outcomes when this study ends.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment with Sofosbuvir based HCV Therapy
Prospective and retrospective treatment for HCV
Harvoni
Treatment of Hepatitis C with sofosbuvir based HCC therapy
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Harvoni
Treatment of Hepatitis C with sofosbuvir based HCC therapy
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Liver transplant candidates (listed) and decompensated cirrhotics (not listed) for liver transplant
1. Treated with sofosbuvir based DAA for any duration since 2014
2. Age \>18 years at time of treatment
3. Pre-treatment Child's Pugh score of 7 or greater
4. Pre-treatment laboratory MELD \>=6 and \<=0
5. Survived at least 12 weeks after start of treatment
6. HIV-positive on stable ART for at least 4 weeks pre-treatment
7. Chronic HCV infection with at least one measurement of plasma HCV RNA \>= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
8. HCV genotype 1, 4, 5 or 6
Liver transplant recipients
1. Treated with sofosbuvir based DAA post liver transplant for any duration since 2014
2. Liver transplant from 2000 to current
3. Age \>18 years at time of treatment
4. Treated initiated at least 1 month post-liver transplant
5. Post-LT stage of liver disease documented within the prior year of treatment start date by standard of care methods of liver staging
6. Survived at least 12 weeks after start of treatment
7. HIV-positive on stable ART for at least 4 weeks pre-treatment
8. Chronic HCV infection with at least one measurement of plasma HCV RNA \>= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
9. Fibrosis staging done within 1 year of start of DAA therapy
10. HCV genotype 1, 4, 5 or 6
1. Over 18 years of age at screening
2. Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
3. Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
4. Have HIV-1 infection and either:
1. On HIV medications (antiretrovirals) for at least 4 weeks WITH
* An HIV viral load less than the level of detection OR
2. On no HIV medications for at least 8 weeks WITH:
* A CD4 count of 500 cells/mm3 or more OR
* HIV viral load of \< 500 copies/mL with a stable CD4 count for at least 3 months
5. Chronic HCV infection as documented by at least one measurement of plasma HCV RNA \>= 1,000 IU/mL during screening and at least one of the following:
A positive anti-HCV antibody, HCV RNA, or an HCV genotype test at least 12 months prior to baseline (Day 0) visit together with positive HCV RNA test
6. HCV genotype 1, 4, 5 or 6
7. The use of an anti-HCV positive donor is allowed for participants who have detectable HCV RNA at the time of transplant.
8. The use of an HIV+ donor is allowed if the participant is enrolled in an IRB approved HOPE Act protocol at the transplant site. If the HIV+ donor is also HCV co-infected, then the recipient must have detectable HCV RNA at the time of transplant.
9. Able to effectively communicate with the Investigator and other center personnel.
10. Willing to give written informed consent and comply with the study restrictions and requirements.
11. Willingness to allow stored blood or tissue samples to be used in the future for studying liver disease and immune function.
12. Willingness to permit HLA typing to be performed.
13. Have a transplant team available for all primary and transplant-related care.
14. If not yet transplanted: expected to be at least 12 weeks prior to transplant in order to complete treatment course.
15. If not yet transplanted: Must have prior standard of care liver staging consistent with F4.
16. If not yet transplanted: For pre-LT patients with HCC, they must meet Milan criteria at time of enrollment to be eligible
17. If post-liver transplant, must be at least 1 month since transplant procedure to begin treatment.
18. If post-liver transplant, liver disease staging must be documented within the prior year by standard of care methods of liver staging
Exclusion Criteria
* Enrollment will be targeted to occur at least 12 weeks prior to anticipated transplant date.
* Screening laboratory MELD \>=6 and \<=20 (NIH) or \<=30 (non-NIH sites)
Post-liver transplant recipients
* Recipients with evidence of recurrent HCV viremia
* Subjects with compensated and decompensated liver disease
* Screening laboratory MELD \>=6 and \<=20 (NIH) or \<=30 (non-NIH sites)
* Life expectation of \>12 weeks
1. Positive HBsAg at screening.
2. History of any other clinically active chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, \>=1 antitrypsin deficiency, alcoholic liver disease, and toxin exposures).
3. Treatment with unlicensed herbal/natural remedies suggested to be taken for hepatitis treatment, such as Milk thistle, St. Johns Wort or Cats Claw, within 28 days of start of treatment
4. Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
5. Any prior exposure to an HCV NS5a specific inhibitor
6. A personal history of or first degree relative with a history of Torsade de pointes.
7. Abnormal hematological and biochemical parameters, including:
1. Hemoglobin \< 8g/dL
2. Estimated GFR, calculated by the CKD-EPI equation, \<30 mL/min/ per 1.73 m2
3. Sodium \<120 mmol/L
8. History of major organ transplantation other than liver or kidney transplantation.
9. Difficulty with blood collection/poor venous access for phlebotomy that would prevent the collection of study required samples
10. Infection requiring systemic antibiotics at the time of screening
11. Active or recent history (≤ 6 months) of drug or alcohol abuse
12. Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
13. Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration.
14. Any medications prohibited (see table 2 in section 8.11) within 28 days prior to Day 0 visit and likely required during study treatment period
15. History of clinically significant drug allergy to nucleoside/nucleotide analogs.
16. History or current evidence of psychiatric illness, endocrine, immunologic disorder, pulmonary, cardiac disease, seizure disorder, cancer or other conditions that in the opinion of the investigator makes the patient unsuitable for the study. Chronic medical conditions, especially if treated with medications (such as hypertension), must be stable at the time of screening. No new therapies should be started within 28 days prior to the study that may confound the assessment of study drug safety.
17. Participation in a clinical study (other than an IRB approved HOPE Act protocol involving the utilization of an HIV+ donor) in which an investigational drug, biologic, or device was received within 12 weeks prior to first dose administration.
18. Pregnant/Breastfeeding women
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Icahn School of Medicine at Mount Sinai
OTHER
Columbia University
OTHER
University of Pennsylvania
OTHER
University of Maryland, College Park
OTHER
Georgetown University
OTHER
Johns Hopkins University
OTHER
National Institutes of Health Clinical Center (CC)
NIH
University of California, San Francisco
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Peter Stock, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Henry Masur, MD
Role: PRINCIPAL_INVESTIGATOR
National Institutes of Health Clinical Center (CC)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California, San Francisco
San Francisco, California, United States
Georgetown University
Washington D.C., District of Columbia, United States
University of Maryland
Baltimore, Maryland, United States
Johns Hopkins Medical Center
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Mt. Sinai Medical Center
New York, New York, United States
Columbia University
New York, New York, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form: Retrospective Informed Consenst
Document Type: Informed Consent Form: Prospective Informed Consent
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
12044
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.