Study of Oral Treatments for Hepatitis C (PRIORITIZE)

THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: EBR/GZR (elbasvir/grazoprevir); Drug: Ribavirin; Drug: SOF/LDV (sofosbuvir/ledipasvir); Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

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.

• Study Type: Interventional
• Enrollment (Actual): 1275
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Liver Wellness Center
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92103
      • UCSD Medical Center
    • San Francisco, California, United States, 94143
      • Univ of California, San Francisco
    • San Francisco, California, United States, 94110
      • UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University Digestive Diseases
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Gainesville, Florida, United States, 32610-0272
      • University of Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida, Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami/Schiff Center for Liver Diseases
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Internal Medicine Associates of Wellstar Atlanta Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60647
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • John Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • GI Associates & Endoscopy Center
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Ctr
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • New York Langone Medical Center
    • New York, New York, United States, 10003
      • Mt. Sinai Beth Israel
    • Valatie, New York, United States, 12184
      • Mountain View Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • Research Specialist of Texas
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EBR/GZR (elbasvir/grazoprevir) with RBV; Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV) 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).	Drug: EBR/GZR (elbasvir/grazoprevir); Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks; Other Names: Zepatier; Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Names: RBV
Active Comparator: EBR/GZR (elbasvir/grazoprevir); Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)	Drug: EBR/GZR (elbasvir/grazoprevir); Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks; Other Names: Zepatier
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir) with RBV; Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) (Harvoni) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (at discretion of provider). RBV taken as 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.	Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Names: RBV; Drug: SOF/LDV (sofosbuvir/ledipasvir); Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider); Other Names: Harvoni® (sofosbuvir/ledipasvir)
Active Comparator: SOF/LDV (sofosbuvir/ledipasvir); Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)	Drug: SOF/LDV (sofosbuvir/ledipasvir); Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider); Other Names: Harvoni® (sofosbuvir/ledipasvir)
Active Comparator: PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only); Patients received Pr0D (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) orally daily with food for 12 to 24 weeks with RBV (Ribavirin). Ombitasvir/Paritaprevir/Ritonavir (12.5/75/50 mg/tablet) -2 tablets once daily with food for 12 to 24 weeks and 1 dasabuvir tablet (250 mg) twice daily with food for 12 to 24 weeks. RBV (200 mg/pill) 1-3 pills/day, 1-2 times/day (use and dosage at provider discretion). Total daily RBV dosage ranged from 200 to 1200 mg.	Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only); Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider); Other Names: Viekira Pak/Viekira
Active Comparator: PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir); Patients received 2 ombitasvir/paritaprevir/ritonavir tablets (12.5/75/50 mg) once daily and 1 dasabuvir (250 mg) tablet twice daily with food for 12 to 24 weeks without Ribavirin (as per provider instructions)	Drug: Ribavirin; 200 mg pills (1-3 pills, 1-2 times per day); Other Names: RBV; Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only); Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider); Other Names: Viekira Pak/Viekira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider). mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2.	12 weeks post-treatment
Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2.	12-24 weeks post HCV treatment
Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation	SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only.	12 weeks post-treatment
Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)	SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site). Number of subjects reflects participants randomized during Phase 1 only.	12 -24 weeks post-treatment
Mean Change in Headache-PRO Scores -Phase 1	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom.	Baseline to On-Treatment
Mean Change in Headache-EBR/GZR and SOF/LDV	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD	Baseline to On-Treatment
Median Change in Headache -Phase 1	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD	12 weeks (Baseline and Average On-treatment Score)
Median Change in Headache-Phase 2	Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD	Baseline -on Treatment (12-16 weeks)
Mean Change in Nausea/Vomiting PRO Score -Phase 1	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status.	Baseline to On-Treatment
Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF	Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting. Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment. A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.	Baseline and Average On-Treatment Score
Median Change in Nausea PRO Score -Phase 1	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.	Baseline to end of treatment
Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV	Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement. The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.	Baseline- On Treatment (up to 16 weeks)
Mean Change in Fatigue PRO Score -Phase 1	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.	Baseline to On-treatment
Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.	Baseline and Average On-Treatment Score
Median Change in Fatigue -Phase 1	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.	Baseline to End of Treatment
Median Change in Fatigue-Phase 2	Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.	Baseline-On Treatment (up to 16 weeks)
Mean Change in HCV- PRO- Phase 1	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.	Baseline to End of Treatment
Median Change in HCV-PRO (Overall Well Being) -Phase 1	HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.	Baseline to End of Treatment
Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2	HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.	End of Treatment - Baseline
16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs	Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms). Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients.	12 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Non-Adherence Probability Estimates	The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being "Non-adherent" if any response was > 1, otherwise they were coded as "Adherent". Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD	12-16 weeks of HCV treatment
Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation	Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement.	1 year post treatment discontinuation (Early post-tx)
Post-treatment Progression/Regression of Liver Disease-Fib-4	Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis.	Baseline to up to 3 years post treatment discontinuation
Change in Functional Status (HCV-PRO) Within Treatment	HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement. Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.	Treatment start date up to 2 years post-treatment
Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF	The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)	Treatment start date through treatment completion (up to 24 weeks)
HCV SVR Durability -No Cirrhosis	Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.	24 weeks post-end of treatment up to 153 weeks
HCV SVR Durability-Patients With Cirrhosis	Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.	Up to 132 weeks post HCV treatment
Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2	Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen	12 weeks post HCV treatment

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Patient-Centered Outcomes Research Institute; Merck Sharp & Dohme LLC; AbbVie
• Investigators: Principal Investigator: David R Nelson, MD, University of Florida

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): June 13, 2019
• Study Completion (Actual): September 2, 2020

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): June 1, 2016

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Hepatitis C
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Sofosbuvir; Ribavirin; Ritonavir; Ledipasvir; Grazoprevir; Elbasvir-grazoprevir drug combination
• Other Study ID Numbers: 16-1234; PCORI-1503-27891 (Other Identifier: PCORI); IRB201501162 (Other Identifier: New UF IRB-01)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No