Clinical trial NCT02786537: Study of Oral Treatments for Hepatitis C
Official title: THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Merck Sharp & Dohme LLC
name: AbbVie
First posted: 2016-06-01
Enrollment: 1275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase 1 of this study compared the effectiveness of 3 approved DAA (direct-acting antiviral) HCV treatment regimens to learn whether they worked equally well under real-world conditions. Phase 2 of this study began early 2017 with removal of 1 DAA regimen, limiting randomization to just 2 FDA approved DAA regimens. Patients receiving HCV therapy in community and academic clinics were offered the opportunity to consent to be randomly assigned to one of three (phase 1) or one of two (phase 2) regimens and observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management were assumed by usual care conditions, and patient-reported outcomes were collected outside clinic in keeping with pragmatic design principles.

Detailed description: In Phase 1 of this study, consented patients were randomized to 1 of the following 3 HCV DAA treatments: 1) Harvoni® (SOF/LDV) 2) Viekira Pak™ (PrOD) 3) Zepatier™ (EBR/GZR) with the optional addition of Ribavirin (RBV) and the length of treatment determined by the individual provider.

In Phase 2 of this study, consented patients were randomized to 1 of 2 FDA approved HCV treatments: Harvoni® or Zepatier™. Both Phase 1 and Phase 2 subjects had up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (following appropriate additional consent). The results of testing determined whether a genotype 1a subject randomized to Zepatier would be provided 12 or 16 wks of Zepatier.

Following enrollment/randomization, participants completed patient reported outcome questionnaires (PROs) via electronic device or telephone. Following baseline/randomization, participants were asked to complete surveys again at Wk 4 of treatment, End of Treatment, 1 and 3 year post treatment. Patients continued standard medical care throughout study. Data was abstracted from test results and medical records throughout treatment and for up to 3 years post treatment.

Eligibility criteria: Inclusion Criteria:

* HCV Genotype 1a or 1b
* Adult patients (age 18 years or older)
* Patients being prescribed HCV treatment who can begin treatment with any of the three HCV treatments being studied (Harvoni (SOF/LDV), Viekira Pak (PrOD) (Phase 1 only), or Zepatier (EBR/GZR))

Exclusion Criteria:

* Inability to provide written informed consent
* HARVONI® is not a covered drug on benefits formulary
* Current or historical evidence of hepatic decompensation (variceal bleeding, hepatic encephalopathy, or ascites)
* Child Pugh (CTP) B or C Cirrhosis (documented CTP calculation is required)
* Pregnant or breastfeeding women

Primary outcomes:
measure: Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV
timeFrame: 12 weeks post-treatment
measure: Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
timeFrame: 12-24 weeks post HCV treatment
measure: Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation
timeFrame: 12 weeks post-treatment
measure: Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
timeFrame: 12 -24 weeks post-treatment
measure: Mean Change in Headache-PRO Scores -Phase 1
timeFrame: Baseline to On-Treatment
measure: Mean Change in Headache-EBR/GZR and SOF/LDV
timeFrame: Baseline to On-Treatment
measure: Median Change in Headache -Phase 1
timeFrame: 12 weeks (Baseline and Average On-treatment Score)
measure: Median Change in Headache-Phase 2
timeFrame: Baseline -on Treatment (12-16 weeks)
measure: Mean Change in Nausea/Vomiting PRO Score -Phase 1
timeFrame: Baseline to On-Treatment
measure: Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF
timeFrame: Baseline and Average On-Treatment Score
measure: Median Change in Nausea PRO Score -Phase 1
timeFrame: Baseline to end of treatment
measure: Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV
timeFrame: Baseline- On Treatment (up to 16 weeks)
measure: Mean Change in Fatigue PRO Score -Phase 1
timeFrame: Baseline to On-treatment
measure: Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV
timeFrame: Baseline and Average On-Treatment Score
measure: Median Change in Fatigue -Phase 1
timeFrame: Baseline to End of Treatment
measure: Median Change in Fatigue-Phase 2
timeFrame: Baseline-On Treatment (up to 16 weeks)
measure: Mean Change in HCV- PRO- Phase 1
timeFrame: Baseline to End of Treatment
measure: Median Change in HCV-PRO (Overall Well Being) -Phase 1
timeFrame: Baseline to End of Treatment
measure: Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2
timeFrame: End of Treatment - Baseline
measure: 16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs
timeFrame: 12 weeks post treatment
Secondary outcomes:
measure: Treatment Non-Adherence Probability Estimates
timeFrame: 12-16 weeks of HCV treatment
measure: Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation
timeFrame: 1 year post treatment discontinuation (Early post-tx)
measure: Post-treatment Progression/Regression of Liver Disease-Fib-4
timeFrame: Baseline to up to 3 years post treatment discontinuation
measure: Change in Functional Status (HCV-PRO) Within Treatment
timeFrame: Treatment start date up to 2 years post-treatment
measure: Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF
timeFrame: Treatment start date through treatment completion (up to 24 weeks)
measure: HCV SVR Durability -No Cirrhosis
timeFrame: 24 weeks post-end of treatment up to 153 weeks
measure: HCV SVR Durability-Patients With Cirrhosis
timeFrame: Up to 132 weeks post HCV treatment
measure: Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2
timeFrame: 12 weeks post HCV treatment
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Liver Wellness Center
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
state: California
city: San Francisco
country: United States
facility: Univ of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale University Digestive Diseases
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami/Schiff Center for Liver Diseases
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Internal Medicine Associates of Wellstar Atlanta Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Lutherville
country: United States
facility: John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Flowood
country: United States
facility: GI Associates & Endoscopy Center
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Ctr
state: Nebraska
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: New York
country: United States
facility: Mt. Sinai Beth Israel
state: New York
city: New York
country: United States
facility: New York Langone Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valatie
country: United States
facility: Mountain View Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Research Specialist of Texas
state: Texas
city: Richmond
country: United States
facility: Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Florida
name: David R Nelson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Evon DM, Dong M, Reeve BB, Peter J, Michael L, Lok AS, Nelson DR, Stewart PW. Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. J Viral Hepat. 2022 Sep;29(9):795-806. doi: 10.1111/jvh.13716. Epub 2022 Jun 15.
citation: Sulkowski MS, Moon JS, Sherman KE, Morelli G, Darling JM, Muir AJ, Khalili M, Fishbein DA, Hinestrosa F, Shiffman ML, Di Bisceglie A, Rajender Reddy K, Pearlman B, Lok AS, Fried MW, Stewart PW, Peter J, Wadsworth S, Kixmiller S, Sloan A, Vainorius M, Horne PM, Michael L, Dong M, Evon DM, Segal JB, Nelson DR; PRIORITIZE Study Team. A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study. Hepatology. 2021 Dec;74(6):2952-2964. doi: 10.1002/hep.32053. Epub 2021 Aug 26.