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Study of Oral Treatments for Hepatitis C (PRIORITIZE)

Primary Purpose

Chronic Hepatitis C

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

SOF/LDV (sofosbuvir/ledipasvir)

PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

EBR/GZR (elbasvir/grazoprevir)

Ribavirin

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Liver Wellness Center
Stanford University
UCSD Medical Center
UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
Univ of California, San Francisco
Yale University Digestive Diseases
Georgetown University
Howard University
University of Florida
University of Florida, Jacksonville
University of Miami/Schiff Center for Liver Diseases
Orlando Immunology Center
Internal Medicine Associates of Wellstar Atlanta Medical Center
Northwestern University
Northwestern University
Indiana University Medical Center
John Hopkins University
Massachusetts General Hospital
University of Michigan
University of Minnesota
GI Associates & Endoscopy Center
Saint Louis University
University of Nebraska Medical Ctr
Southwest CARE Center
Mt. Sinai Beth Israel
New York Langone Medical Center
Weill Cornell Medical College
Columbia University Medical Center
Mountain View Medical Center
University of North Carolina at Chapel Hill
Duke University Medical Center
University of Cincinnati
University of Pennsylvania
Research Specialist of Texas
Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)
Virginia Commonwealth University
Virginia Mason Medical Center
University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Arm Label

EBR/GZR (elbasvir/grazoprevir) with RBV

EBR/GZR (elbasvir/grazoprevir)

SOF/LDV (sofosbuvir/ledipasvir) with RBV

SOF/LDV (sofosbuvir/ledipasvir)

PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only)

PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir)

Arm Description

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).

Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)

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.

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)

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.

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)

Outcomes

Primary Outcome Measures

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.

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.

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.

Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)

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.

Mean Change in Headache-EBR/GZR and SOF/LDV

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

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

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.

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.

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.

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.

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.

Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV

Median Change in Fatigue -Phase 1

Median Change in Fatigue-Phase 2

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.

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.

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.

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.

Secondary Outcome Measures

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

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.

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.

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.

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)

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.

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.

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

Full Information

NCT ID

NCT02786537

First Posted

May 17, 2016

Last Updated

December 1, 2021

Sponsor

University of Florida

Collaborators

Patient-Centered Outcomes Research Institute, Merck Sharp & Dohme LLC, AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02786537

Brief Title

Study of Oral Treatments for Hepatitis C

Acronym

PRIORITIZE

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

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

June 2016 (undefined)

Primary Completion Date

June 13, 2019 (Actual)

Study Completion Date

September 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

Collaborators

Patient-Centered Outcomes Research Institute, Merck Sharp & Dohme LLC, AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

Keywords

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1275 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EBR/GZR (elbasvir/grazoprevir) with RBV

Arm Type

Active Comparator

Arm Description

Arm Title

EBR/GZR (elbasvir/grazoprevir)

Arm Type

Active Comparator

Arm Description

Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)

Arm Title

SOF/LDV (sofosbuvir/ledipasvir) with RBV

Arm Type

Active Comparator

Arm Description

Arm Title

SOF/LDV (sofosbuvir/ledipasvir)

Arm Type

Active Comparator

Arm Description

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)

Arm Title

PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only)

Arm Type

Active Comparator

Arm Description

Arm Title

PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

SOF/LDV (sofosbuvir/ledipasvir)

Other Intervention Name(s)

Harvoni® (sofosbuvir/ledipasvir)

Intervention Description

Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

Intervention Type

Drug

Intervention Name(s)

PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

Other Intervention Name(s)

Viekira Pak/Viekira

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

EBR/GZR (elbasvir/grazoprevir)

Other Intervention Name(s)

Zepatier

Intervention Description

Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks

Intervention Type

Drug

Intervention Name(s)

Ribavirin

Other Intervention Name(s)

RBV

Intervention Description

200 mg pills (1-3 pills, 1-2 times per day)

Primary Outcome Measure Information:

Title

Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV

Description

Time Frame

12 weeks post-treatment

Title

Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)

Description

Time Frame

12-24 weeks post HCV treatment

Title

Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation

Description

Time Frame

12 weeks post-treatment

Title

Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)

Description

Time Frame

12 -24 weeks post-treatment

Title

Mean Change in Headache-PRO Scores -Phase 1

Description

Time Frame

Baseline to On-Treatment

Title

Mean Change in Headache-EBR/GZR and SOF/LDV

Description

Time Frame

Baseline to On-Treatment

Title

Median Change in Headache -Phase 1

Description

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

Time Frame

12 weeks (Baseline and Average On-treatment Score)

Title

Median Change in Headache-Phase 2

Description

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

Time Frame

Baseline -on Treatment (12-16 weeks)

Title

Mean Change in Nausea/Vomiting PRO Score -Phase 1

Description

Time Frame

Baseline to On-Treatment

Title

Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF

Description

Time Frame

Baseline and Average On-Treatment Score

Title

Median Change in Nausea PRO Score -Phase 1

Description

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.

Time Frame

Baseline to end of treatment

Title

Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV

Description

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.

Time Frame

Baseline- On Treatment (up to 16 weeks)

Title

Mean Change in Fatigue PRO Score -Phase 1

Description

Time Frame

Baseline to On-treatment

Title

Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV

Description

Time Frame

Baseline and Average On-Treatment Score

Title

Median Change in Fatigue -Phase 1

Description

Time Frame

Baseline to End of Treatment

Title

Median Change in Fatigue-Phase 2

Description

Time Frame

Baseline-On Treatment (up to 16 weeks)

Title

Mean Change in HCV- PRO- Phase 1

Description

Time Frame

Baseline to End of Treatment

Title

Median Change in HCV-PRO (Overall Well Being) -Phase 1

Description

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.

Time Frame

Baseline to End of Treatment

Title

Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2

Description

Time Frame

End of Treatment - Baseline

Title

16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs

Description

Time Frame

12 weeks post treatment

Secondary Outcome Measure Information:

Title

Treatment Non-Adherence Probability Estimates

Description

Time Frame

12-16 weeks of HCV treatment

Title

Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation

Description

Time Frame

1 year post treatment discontinuation (Early post-tx)

Title

Post-treatment Progression/Regression of Liver Disease-Fib-4

Description

Time Frame

Baseline to up to 3 years post treatment discontinuation

Title

Change in Functional Status (HCV-PRO) Within Treatment

Description

Time Frame

Treatment start date up to 2 years post-treatment

Title

Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF

Description

The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)

Time Frame

Treatment start date through treatment completion (up to 24 weeks)

Title

HCV SVR Durability -No Cirrhosis

Description

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.

Time Frame

24 weeks post-end of treatment up to 153 weeks

Title

HCV SVR Durability-Patients With Cirrhosis

Description

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.

Time Frame

Up to 132 weeks post HCV treatment

Title

Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2

Description

Time Frame

12 weeks post HCV treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David R Nelson, MD

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

Liver Wellness Center

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

Stanford University

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

UCSD Medical Center

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

UCSF/Zuckerberg San Francisco General Hospital and Trauma Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94110

Country

United States

Facility Name

Univ of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Yale University Digestive Diseases

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Georgetown University

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Howard University

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20060

Country

United States

Facility Name

University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610-0272

Country

United States

Facility Name

University of Florida, Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Facility Name

University of Miami/Schiff Center for Liver Diseases

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Orlando Immunology Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

Internal Medicine Associates of Wellstar Atlanta Medical Center

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30312

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60647

Country

United States

Facility Name

Indiana University Medical Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

John Hopkins University

City

Lutherville

State/Province

Maryland

ZIP/Postal Code

21093

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

GI Associates & Endoscopy Center

City

Flowood

State/Province

Mississippi

ZIP/Postal Code

39232

Country

United States

Facility Name

Saint Louis University

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63104

Country

United States

Facility Name

University of Nebraska Medical Ctr

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

Facility Name

Southwest CARE Center

City

Santa Fe

State/Province

New Mexico

ZIP/Postal Code

87505

Country

United States

Facility Name

Mt. Sinai Beth Israel

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

Facility Name

New York Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Mountain View Medical Center

City

Valatie

State/Province

New York

ZIP/Postal Code

12184

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

University of Cincinnati

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45267

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Research Specialist of Texas

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23226

Country

United States

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23284

Country

United States

Facility Name

Virginia Mason Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98101

Country

United States

Facility Name

University of Washington

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35657133

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.

Results Reference

derived

PubMed Identifier

34255381

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.

Results Reference

derived

Learn more about this trial

Study of Oral Treatments for Hepatitis C

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