<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03791814</url>
  </required_header>
  <id_info>
    <org_study_id>MATCH-D study</org_study_id>
    <nct_id>NCT03791814</nct_id>
  </id_info>
  <brief_title>A Prospective Cohort Study to Improve HCV Care in Dialysis Patients</brief_title>
  <acronym>MATCH-D</acronym>
  <official_title>A Prospective Cohort Study to Improve HCV Care Using Multidisciplinary Approach to the Treatment of Chronic Hepatitis C in Dialysis Patients: The MATCH-D Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Albert Einstein Healthcare Network</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Davita Clinical Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Albert Einstein Healthcare Network</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hepatitis C virus (HCV) infects an estimated 185 million individuals worldwide and 3.4&#xD;
      million to 4.4 million people in the United States. Approximately 80% of acutely infected HCV&#xD;
      patients progress to chronic infection, 20% of whom develop cirrhosis within 25 years, with&#xD;
      25% of patients with cirrhosis developing hepatocellular carcinoma and/or decompensated liver&#xD;
      disease. Hepatitis C virus is the primary cause of liver transplantation in the United&#xD;
      States.&#xD;
&#xD;
      There are 6 known genotypes of HCV. The most common genotypes in the United States are&#xD;
      genotype 1 (subtypes 1a and 1b), 2, and 3, which together comprise 97% of all infections.&#xD;
&#xD;
      In chronic kidney disease (CKD) patients, the prevalence of HCV infection is higher than in&#xD;
      the general population. Patients with impaired kidney function have limited therapeutic&#xD;
      options. The US Food and Drug Administration (FDA) recently approved Elbasvir/Grazopevir for&#xD;
      treatment of genotype 1 and 4 infection in CKD patients including those on hemodialysis.&#xD;
&#xD;
      At our institution, the Multidisciplinary Approach to the Treatment of Chronic Hepatitis C&#xD;
      (MATCH) Initiative is a program which was first implemented to increase screening, diagnosis&#xD;
      and treatment of HCV by actively incorporating primary care providers (PCP) at every step of&#xD;
      the HCV care process. Following implementation of MATCH, early data indicates, marked&#xD;
      increase in screening high risk and baby-boomer cohorts, as well as safe and effective&#xD;
      treatment of HCV cases at the primary provider setting. The initiative proved that active&#xD;
      participation of PCPs in the care of HCV reduced the treatment lag by 71% compared to&#xD;
      traditional care of referring HCV cases to specialized care (Gastroenterology or Hepatology)&#xD;
      while keeping similar SVR. We intend to expand the program to improve quality of care for HCV&#xD;
      patients in dialysis center. We propose active involvement of dialysis clinical staff&#xD;
      including nephrologist, to increase HCV screening rate, promote timely diagnosis and&#xD;
      treatment of CHC in patient with end-stage renal disease.&#xD;
&#xD;
      This study is being conducted to evaluate real-world effectiveness of HCV DAA therapy in CHC&#xD;
      hemodialysis patients when the DAA-treatment is managed and monitored by the clinical staff&#xD;
      of hemodialysis center.&#xD;
&#xD;
      Primary objective: To determine sustained virologic response (SVR) rates attained with&#xD;
      open-label Zepatier administered through hemodialysis center under the supervision of a&#xD;
      nephrologist in chronic hepatitis C infected (CHC) patient currently on hemodialysis.&#xD;
&#xD;
      Secondary objective:&#xD;
&#xD;
        1. To estimate prevalence of HCV infection, severity of fibrosis (using non-invasive&#xD;
           measures), and HCV detection rate in patients with End stage renal disease on&#xD;
           hemodialysis.&#xD;
&#xD;
        2. To calculate the average treatment-lag time (time from HCV diagnosis to submission of&#xD;
           treatment approval).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is being conducted to evaluate real-world effectiveness of HCV DAA therapy in CHC&#xD;
      hemodialysis patients when the DAA-treatment is managed and monitored by the nephrologist of&#xD;
      hemodialysis center.&#xD;
&#xD;
      Hepatitis C virus (HCV) infects an estimated 185 million individuals worldwide (1) and 3.4&#xD;
      million to 4.4 million people in the United States.(2) Approximately 80% of acutely infected&#xD;
      HCV patients progress to chronic infection, 20% of whom develop cirrhosis within 25 years,&#xD;
      with 25% of patients with cirrhosis developing hepatocellular carcinoma and/or decompensated&#xD;
      liver disease.(3) Hepatitis C virus is the primary cause of liver transplantation in the&#xD;
      United States.(4) There are 6 known genotypes of HCV. The most common genotypes in the United&#xD;
      States are genotype 1 (subtypes 1a and 1b), 2, and 3, which together comprise 97% of all&#xD;
      infections.(5) Since the discovery of HCV in 1989 (6) strategies to cure the infection have&#xD;
      evolved dramatically. A cure is defined as a sustained virologic response (SVR) and consists&#xD;
      of undetectable levels of plasma HCV RNA 12 or 24 weeks after therapy completion.(7)&#xD;
      Treatment of HCV has evolved rapidly and has led to improved rates of SVR.&#xD;
&#xD;
      Although these highly effective therapies for hepatitis C virus (HCV) infection have&#xD;
      revolutionized treatment, only a few patients are able to receive treatment.(8) Barriers&#xD;
      arising at multiple levels, from diagnosis to specialist referral, that still need to be&#xD;
      overcome to move toward disease eradication.(9) In chronic kidney disease (CKD) patients, the&#xD;
      prevalence of HCV infection is higher than in the general population. Testing for HCV in&#xD;
      hemodialysis patients should be repeated every 6 months.(10) The national study on&#xD;
      dialysis-associated diseases was published in 2002 and represents the infection statistics&#xD;
      from dialysis center nationwide.(11) The overall estimated prevalence of HCV antibody in this&#xD;
      study was 7.8%.&#xD;
&#xD;
      In addition, patients with impaired kidney function have limited therapeutic options. The US&#xD;
      Food and Drug Administration (FDA) recently approved Elbasvir/Grazopevir for treatment of&#xD;
      genotype 1 and 4 infection in CKD patients including those on hemodialysis.&#xD;
&#xD;
      At our institution, the Multidisciplinary Approach to the Treatment of Chronic Hepatitis C&#xD;
      (MATCH) Initiative is a program which was first implemented to increase screening, diagnosis&#xD;
      and treatment of HCV by actively incorporating primary care providers (PCP) at every step of&#xD;
      the HCV care process. Following implementation of MATCH, early data indicates, marked&#xD;
      increase in screening high risk and baby-boomer cohorts, as well as safe and effective&#xD;
      treatment of HCV cases at the primary provider setting. The initiative proved that active&#xD;
      participation of PCPs in the care of HCV reduced the treatment lag by 71% compared to&#xD;
      traditional care of referring HCV cases to specialized care (Gastroenterology or Hepatology)&#xD;
      while keeping similar SVR. (13) We intend to expand the program to improve quality of care&#xD;
      for HCV patients in dialysis center. We propose active involvement of dialysis clinical staff&#xD;
      including nephrologist, to increase HCV screening rate, promote timely diagnosis and&#xD;
      treatment of CHC in patient with end-stage renal disease.&#xD;
&#xD;
      Rationale of the study- We will perform a phase IV study to prove real world effectiveness of&#xD;
      Zepatier in successful treatment of CHC in patients on chronic hemodialysis at hemodialysis&#xD;
      centers, when administered under the supervision of a nephrologist. The study will be&#xD;
      conducted in the selected collaborative hemodialysis centers.&#xD;
&#xD;
      Zepatier Open-label Zepatier (grazoprevir 100 mg and elbasvir 50 mg) will be administered in&#xD;
      this study.(14, 15) Zepatier is a fixed-dose combination tablet without ribavirin. GZR is an&#xD;
      HCV NS3/4a inhibitor while EBR is an HCV NS5A inhibitor. Both grazoprevir and elbasvir are&#xD;
      direct-acting antivirals, which together form an effective therapy for HCV and reduce the&#xD;
      likelihood and effects of long-term liver-related HCV complications.&#xD;
&#xD;
      Zepatier has been evaluated globally in multiple phase I, II, and III trials to treat HCV.&#xD;
      (14, 15) Randomized, placebo-controlled trials have been carried out, which led to FDA&#xD;
      approval for Zepatier as a treatment for genotype 1 and 4 HCV.&#xD;
&#xD;
      As of July 1, 2015, a diverse population of over 1000 HCV patients has been exposed to&#xD;
      Zepatier either as a single agent or in combination with ribavirin or sofosbuvir in phase&#xD;
      I/II/III studies. Zepatier has been generally well tolerated at doses of 50-100 mg GZR and 50&#xD;
      mg EBR orally once daily. It has been comparably effective across all subgroups it has been&#xD;
      tested in, including non-cirrhotic and/or treatment-naïve subjects. (14, 15) Headaches,&#xD;
      fatigue, and nausea represent the most common adverse drug reactions with Zepatier.3,4 Other&#xD;
      drug-related adverse events have included arthralgia, insomnia, diarrhea, dizziness, pyrexia,&#xD;
      and asthenia. (14, 15) Drug-related serious adverse events are uncommon, but include allergic&#xD;
      reactions, possible adverse interactions with other medications, or elevated liver enzymes.&#xD;
      In past Zepatier trials, the majority of the adverse events were reversible. These adverse&#xD;
      events are usually mild or moderate events.&#xD;
&#xD;
      The dosage in our study (100/50 mg daily) is a commonly attainable dose in clinical practice.&#xD;
      Zepatier has shown to be safe for subjects with chronic kidney disease or who are on&#xD;
      hemodialysis. Less than 1% of Zepatier is excreted renally. In Merck's C-SURFER, a phase 1&#xD;
      randomized, controlled Zepatier trial, subjects with advanced kidney disease tolerated the&#xD;
      drug well for the required 12 weeks without dose adjustments. (16) Zepatier trials have&#xD;
      demonstrated a 94-100% success rate achieving HCV RNA levels of &lt;15 IU/ml after 12 weeks of&#xD;
      treatment (SVR-12) among genotype 1 HCV patients. (14, 15) This is a prospective cohort phase&#xD;
      IV study using multidisciplinary approach for the treatment of hepatitis C in hemodialysis&#xD;
      patients. Hemodialysis centers will be used to deliver all HCV related care.&#xD;
&#xD;
      The study will be conducted in the selected collaborative hemodialysis centers in&#xD;
      Philadelphia. In addition to the standard of care (SOC), all subjects with CHC will be&#xD;
      evaluated for HCV DAA therapy: review of clinical records, assessment of the degree of liver&#xD;
      fibrosis using FibroScan, baseline HCV virological tests, HIV and HBV screening, etc.&#xD;
      Baseline and follow-up laboratory tests and FibroScan imaging will be performed at the&#xD;
      Einstein lab or an alternative laboratory if requested by the patient. Baseline clinical&#xD;
      evaluation and follow up focused H/P will be done by the nephrologist at the dialysis unit..&#xD;
      The study coordinator is a MATCH-D navigator and is responsible for compiling supporting&#xD;
      documents for HCV DAA treatment request and fax it to a designated fax number (to mimic&#xD;
      faxing to the payers in real world scenario). Local specialty pharmacy pharmacist (also a&#xD;
      part of the MATCH-D group) will be responsible for providing hepatitis C treatment education&#xD;
      to approved patients, ensure delivery of DAA therapy and monitoring for any drug related&#xD;
      adverse events.&#xD;
&#xD;
      MATCH-D group will comprise of a study coordinator, study investigators, nephrologist,&#xD;
      specialty pharmacy pharmacist, and dialysis unit . The group will meet weekly to review cases&#xD;
      and provide recommendations on diagnosis, DAA selection and assist with HCV treatment This&#xD;
      study will be divided to 3 phases.&#xD;
&#xD;
        1. Training study team, dialysis center clinical staff (Quarterly refresher)&#xD;
&#xD;
        2. Identifying hepatitis C patient and evaluation for treatment&#xD;
&#xD;
        3. Treatment and follow up Phase 1: Training study team and dialysis center clinical staff&#xD;
           education All collaborative hemodialysis centers coordinator and the study team will be&#xD;
           educated for HCV screening, work-up, treatment and study protocol in the first month of&#xD;
           study. There will be refresher course every 3 months.&#xD;
&#xD;
      Phase 2: Identifying hepatitis C patient and evaluation for treatment&#xD;
&#xD;
        1. Patient Screening a. Every dialysis patient will be offered HCV screening every 6 months&#xD;
           as standard of care.&#xD;
&#xD;
           b. HCV Ab with reflex HCV viral load will be ordered.&#xD;
&#xD;
        2. Patient Identification&#xD;
&#xD;
             1. Patients will be assessed for positive HCV Ab and detectable viral load.&#xD;
&#xD;
             2. Nephrologist will notifythe patient with the results.&#xD;
&#xD;
             3. Nephrologist will have the patient complete and sign HIPAA form.&#xD;
&#xD;
             4. Nephrologist will email patient information to the study coordinator.&#xD;
&#xD;
             5. Study coordinator is expected to keep composite record (including the above&#xD;
                results) of all identified patients until enrollment. This record will be utilized&#xD;
                at the Multidisciplinary Meeting.&#xD;
&#xD;
             6. Informed consent will be obtained by the study coordinator.&#xD;
&#xD;
             7. Basic demographic information will be collected.&#xD;
&#xD;
        3. Patient evaluation for treatment&#xD;
&#xD;
             1. Complete blood work and FibroScan imaging will be conducted at Einstein lab or an&#xD;
                alternative laboratory if requested by the patient.&#xD;
&#xD;
             2. Study coordinator is expected to ensure patients have all testing completed.&#xD;
&#xD;
             3. Study coordinator will ensure all patients are tested for FibroScan imaging using&#xD;
                the portable FibroScan® 530 Compact system. .&#xD;
&#xD;
      This trial will enroll approximately 71 compensated cirrhotic and non-cirrhotic, Genotype 1&#xD;
      and 4, HCV patients who are currently on hemodialysis. Non-invasive test will be used to&#xD;
      determine the presence or absence of cirrhosis. All excluded CHC patients will receive&#xD;
      standard of care. Patients who have decompensated cirrhosis or hepatoma will be referred to&#xD;
      the hepatology clinic and receive care by the hepatologist.&#xD;
&#xD;
      Study visits There will be 4 study visits in our study. Subjects may be asked to come early&#xD;
      before dialysis session to have physical examination or Fibroscan.&#xD;
&#xD;
      Screening and Informed consent&#xD;
&#xD;
      During screening period, the following procedures and activities will be performed at&#xD;
      hemodialysis center after the informed consent is signed:&#xD;
&#xD;
        -  Review medical history and physical examination&#xD;
&#xD;
        -  Review medication list&#xD;
&#xD;
        -  Review laboratory data Baseline study • First laboratory tests will be performed at the&#xD;
           Einstein lab or an alternative laboratory if requested by the patientand include: • CBC,&#xD;
           CMP, PT/INR • HCV PCR Viral load&#xD;
&#xD;
             -  HCV PCR genotype&#xD;
&#xD;
             -  HCV NS5A RAV testing&#xD;
&#xD;
             -  HBV screening: HBsAg, HBcAb&#xD;
&#xD;
             -  HIV 1 / 2 Ab screening&#xD;
&#xD;
             -  FibroScan&#xD;
&#xD;
             -  Women of childbearing potential will have a pregnancy test at screening visit.&#xD;
                Phase 3: Treatment and follow up 1. Treatment a. MATCH-D group will review and&#xD;
                discuss identified CHC patients and determine those appropriate for DAA therapy&#xD;
                through the dialysis center, and those who require referral to Liver Center based&#xD;
                on work-up (e.g. decompensated cirrhosis).&#xD;
&#xD;
                i. Patients appropriate for dialysis center treatment and agreeable to treatment&#xD;
                will be enrolled in study.&#xD;
&#xD;
                b. Meeting to occur weekly c. Study coordinator will notify the nephrologist, who&#xD;
                saw patient, by email of the meeting decision. Subsequently, the nephrologist&#xD;
                should notify patient of the decision and a) refer to hepatology if needed or b)&#xD;
                explain need for treatment.&#xD;
&#xD;
                d. Prescription along with pertinent information (e.g. lab results, fibrosis stage,&#xD;
                etc.) will be compiled and sent to local specialty pharmacy by the study&#xD;
                coordinator for all enrolled patients.&#xD;
&#xD;
                e. Specialty pharmacy will:&#xD;
&#xD;
                  1. Provide education to patients about prescribed treatment.&#xD;
&#xD;
                  2. Identify potential drug interactions and notify team.&#xD;
&#xD;
                  3. Oversee delivery of medications. Provide refill reminders to patients or&#xD;
                     dialysis center staff.&#xD;
&#xD;
                  4. Monitor medication adherence.&#xD;
&#xD;
                  5. Keep &quot;database&quot; that is accessible to study coordinator and MATCH-D study&#xD;
                     group Specialty pharmacy will be the investigational pharmacy who is&#xD;
                     expertised in HCV care.&#xD;
&#xD;
      Initiation treatment with Zepatier All subjects will be provided with a 28-day supply of the&#xD;
      study drug and instructed to begin treatment once all tests are done. The study coordinator&#xD;
      will call the patient to ensure treatment has begun for HCV with Zepatier.&#xD;
&#xD;
      As with any scientific protocol, safety will be considered before treating the patients. The&#xD;
      MATCH-D team will evaluate the patient's overall condition and make a judgment on whether&#xD;
      initiating treatment is safe.&#xD;
&#xD;
      Zepatier for 12 weeks or 16 weeks ± Ribavirin will be used to treat HCV genotype 1, 4 in our&#xD;
      patients and will be supplied by Merck &amp; Co.Inc.&#xD;
&#xD;
      Statistical Methods The data will be collected using an Excel spreadsheet and analyzed with&#xD;
      Stata 14.0 (Statacorp., College Town, TX). Descriptive statistics will be used to summarize&#xD;
      the demographic characteristics. Screening rates, treatment rates, and treatment lag (time&#xD;
      from detection to treatment submission) will be calculated. Categorical variables will be&#xD;
      compared using chi square or fischer's exact test whereas continuous variables will be&#xD;
      compared using student's t-test. SVR rates will also be compared with historical controls. P&#xD;
      value of less than 0.05 will be considered statistically significant.&#xD;
&#xD;
      Power/Sample Size:&#xD;
&#xD;
      Power of 0.8 with a p-value of 0.05 were used a priori for sample size calculation. As was&#xD;
      shown in C-SURFER trial recently, SVR of 99% was attained in chronic kidney disease patients&#xD;
      including those on dialysis. Accepting a non-inferiority margin of 5% and similar expected&#xD;
      SVR in our cohort, the sample size was calculated to be 71 patients.&#xD;
&#xD;
      Potential Benefits The subjects will get clinical benefits as the HCV treatment can prevent&#xD;
      cirrhosis and hepatocellular carcinoma in the future. This study also has a potential to&#xD;
      speed up treatment evaluation and the subjects may get the treatment faster.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study was stopped due to difficulty in identifying potential patients.&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">June 30, 2019</completion_date>
  <primary_completion_date type="Actual">June 30, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HCV treatment-lag time</measure>
    <time_frame>12 weeks</time_frame>
    <description>To determine the average treatment-lag time (time from HCV diagnosis to submission of treatment approval) of HCV treatment delivered through hemodialysis centers by nephrologists compared to standard of care via traditional gastroenterology or hepatology centers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence rates</measure>
    <time_frame>12 weeks</time_frame>
    <description>To estimate prevalence of HCV infection, severity of fibrosis (using non-invasive measures), and HCV detection rate in patients with End stage renal disease on hemodialysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sustained virologic response (SVR) rates</measure>
    <time_frame>6 months</time_frame>
    <description>2. To determine sustained virologic response (SVR) rates of open-label Zepatier in chronic hepatitis C infected (CHC) patient who are currently on hemodialysis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Zepatier treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open-label Zepatier (grazoprevir 100 mg and elbasvir 50 mg) will be administered in this study. Daily treatment of Zepatier for a 12-week duration will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zepatier</intervention_name>
    <description>Patients screened as HCV positive will receive Zepatier for 12 weeks.</description>
    <arm_group_label>Zepatier treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be 18 years of age or older on day of signing the informed consent form.&#xD;
&#xD;
          -  Be on long term hemodialysis at any of the selected 4 collaborative hemodialysis&#xD;
             centers&#xD;
&#xD;
          -  Have positive anti-HCV antibody titers and detectable HCV RNA level before or after&#xD;
             the initiation of MATCH-D.&#xD;
&#xD;
          -  HCV genotype 1 and 4&#xD;
&#xD;
          -  Have an HCV treatment status that is one of the following:&#xD;
&#xD;
               1. Treatment naïve: Naive to all anti-HCV treatment&#xD;
&#xD;
               2. Prior IFN or PEG-IFN + Ribavirin Treatment failures: Null responders, Partial&#xD;
                  responders, Relapsers&#xD;
&#xD;
               3. P/R Intolerant: Subjects were intolerant to a prior IFN or PEG-IFN&#xD;
&#xD;
                    -  Ribavirin regimen, Subjects discontinued treatment prematurely and were&#xD;
                       therefore unable to complete a full course of therapy because of&#xD;
                       drug-related toxicity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has evidence of decompensated chronic liver disease such as presence of or history of&#xD;
             - ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or&#xD;
             symptoms of advanced liver disease&#xD;
&#xD;
          -  Have Child-Pugh B or C cirrhosis (these patients will need to be referred to a&#xD;
             hepatologist for HCV therapy)&#xD;
&#xD;
          -  Have a likelihood of receiving a renal transplant or liver transplant during the study&#xD;
             treatment period.&#xD;
&#xD;
          -  Have hepatocellular carcinoma&#xD;
&#xD;
          -  Have other liver disease (which require HCV therapy to be delivered under the&#xD;
             supervision of a hepatologist)&#xD;
&#xD;
          -  A patient with a life expectancy less than 12 months&#xD;
&#xD;
          -  Current untreated chronic hepatitis B infection HBsAg+ patients are excluded. Note:&#xD;
             Patients with HBcAb+ will not be excluded, but will have HBV DNA levels checked and&#xD;
             will be monitored while on DAA therapy and medically managed as considered appropriate&#xD;
             by the PI.&#xD;
&#xD;
          -  Have HIV and currently not under Antiretroviral Therapy (ART)&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Albumin below 3g/dL&#xD;
&#xD;
          -  Platelet count below 75,000&#xD;
&#xD;
          -  Unable to comply with research study visits&#xD;
&#xD;
          -  Poor venous access not allowing screening laboratory collection&#xD;
&#xD;
          -  Have any condition that the investigator considers a contraindication to study&#xD;
             participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eyob Feyssa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Albert Einstein Healthcare Network</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eyob Feyssa, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Albert Einstein Healthcare Network</affiliation>
  </overall_official>
  <reference>
    <citation>Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005 Sep;5(9):558-67. doi: 10.1016/S1473-3099(05)70216-4.</citation>
    <PMID>16122679</PMID>
  </reference>
  <reference>
    <citation>Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int. 2011 Sep;31(8):1090-101. doi: 10.1111/j.1478-3231.2011.02494.x. Epub 2011 Mar 16.</citation>
    <PMID>21745274</PMID>
  </reference>
  <reference>
    <citation>Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, Marinos G, Kaldor JM. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001 Oct;34(4 Pt 1):809-16. doi: 10.1053/jhep.2001.27831.</citation>
    <PMID>11584380</PMID>
  </reference>
  <reference>
    <citation>Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010 Feb;138(2):513-21, 521.e1-6. doi: 10.1053/j.gastro.2009.09.067. Epub 2009 Oct 25.</citation>
    <PMID>19861128</PMID>
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  <reference>
    <citation>Delwart E, Slikas E, Stramer SL, Kamel H, Kessler D, Krysztof D, Tobler LH, Carrick DM, Steele W, Todd D, Wright DJ, Kleinman SH, Busch MP; NHLBI-REDS-II Study Group. Genetic diversity of recently acquired and prevalent HIV, hepatitis B virus, and hepatitis C virus infections in US blood donors. J Infect Dis. 2012 Mar 15;205(6):875-85. doi: 10.1093/infdis/jir862. Epub 2012 Jan 31.</citation>
    <PMID>22293432</PMID>
  </reference>
  <reference>
    <citation>Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359-62. doi: 10.1126/science.2523562.</citation>
    <PMID>2523562</PMID>
  </reference>
  <reference>
    <citation>Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, Abergel A, Pessoa MG, Lin A, Tietz A, Connell EV, Diago M. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology. 2010 Nov;139(5):1593-601. doi: 10.1053/j.gastro.2010.07.009. Epub 2010 Jul 14.</citation>
    <PMID>20637202</PMID>
  </reference>
  <reference>
    <citation>McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2012 Feb;32 Suppl 1(0 1):151-6. doi: 10.1111/j.1478-3231.2011.02706.x.</citation>
    <PMID>22212587</PMID>
  </reference>
  <reference>
    <citation>Konerman MA, Lok AS. Hepatitis C Treatment and Barriers to Eradication. Clin Transl Gastroenterol. 2016 Sep 22;7(9):e193. doi: 10.1038/ctg.2016.50.</citation>
    <PMID>27657495</PMID>
  </reference>
  <reference>
    <citation>Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl. 2008 Apr;(109):S1-99. doi: 10.1038/ki.2008.81. No abstract available.</citation>
    <PMID>18382440</PMID>
  </reference>
  <reference>
    <citation>Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005 Jan-Feb;18(1):52-61. doi: 10.1111/j.1525-139X.2005.18108.x.</citation>
    <PMID>15663766</PMID>
  </reference>
  <reference>
    <citation>AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015 Sep;62(3):932-54. doi: 10.1002/hep.27950. Epub 2015 Aug 4. No abstract available.</citation>
    <PMID>26111063</PMID>
  </reference>
  <reference>
    <citation>Sandhu N, Mulki R, Tosounian S, Wheeler D, Feyssa E, Baumann A. Multidisciplinary Approach to the Treatment of Chronic Hepatitis C: The MATCH Initiative AASLD Abstract presentation. 2017.</citation>
  </reference>
  <reference>
    <citation>Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.</citation>
    <PMID>25895428</PMID>
  </reference>
  <reference>
    <citation>Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.</citation>
    <PMID>25909356</PMID>
  </reference>
  <reference>
    <citation>Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5. Erratum In: Lancet. 2015 Nov 7;386(10006):1824.</citation>
    <PMID>26456905</PMID>
  </reference>
  <reference>
    <citation>Merck Sharp &amp; Dohme Corporation (January 2016). ZEPATIER™ tablets. Highlights of Prescribing Information. 2016.</citation>
  </reference>
  <reference>
    <citation>Merck Sharp &amp; Dohme Corporation (July 2015). Elbasvir (MK-8742). Investigator's Brochure (8th Ed.).2015.</citation>
  </reference>
  <reference>
    <citation>Merck Sharp &amp; Dohme Corporation (July 2015). Grazoprevir (MK-5172). Investigator's Brochure (10th Ed.). 2015.</citation>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>February 25, 2020</last_update_submitted>
  <last_update_submitted_qc>February 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Albert Einstein Healthcare Network</investigator_affiliation>
    <investigator_full_name>Eyob Feyssa</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>HCV treatment</keyword>
  <keyword>Zepatier</keyword>
  <keyword>Dialysis patients</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Elbasvir-grazoprevir drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03791814
org study id: MATCH-D study
nct id: NCT03791814
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Hepatitis C virus (HCV) infects an estimated 185 million individuals worldwide and 3.4
      million to 4.4 million people in the United States. Approximately 80% of acutely infected HCV
      patients progress to chronic infection, 20% of whom develop cirrhosis within 25 years, with
      25% of patients with cirrhosis developing hepatocellular carcinoma and/or decompensated liver
      disease. Hepatitis C virus is the primary cause of liver transplantation in the United
      States.

      There are 6 known genotypes of HCV. The most common genotypes in the United States are
      genotype 1 (subtypes 1a and 1b), 2, and 3, which together comprise 97% of all infections.

      In chronic kidney disease (CKD) patients, the prevalence of HCV infection is higher than in
      the general population. Patients with impaired kidney function have limited therapeutic
      options. The US Food and Drug Administration (FDA) recently approved Elbasvir/Grazopevir for
      treatment of genotype 1 and 4 infection in CKD patients including those on hemodialysis.

      At our institution, the Multidisciplinary Approach to the Treatment of Chronic Hepatitis C
      (MATCH) Initiative is a program which was first implemented to increase screening, diagnosis
      and treatment of HCV by actively incorporating primary care providers (PCP) at every step of
      the HCV care process. Following implementation of MATCH, early data indicates, marked
      increase in screening high risk and baby-boomer cohorts, as well as safe and effective
      treatment of HCV cases at the primary provider setting. The initiative proved that active
      participation of PCPs in the care of HCV reduced the treatment lag by 71% compared to
      traditional care of referring HCV cases to specialized care (Gastroenterology or Hepatology)
      while keeping similar SVR. We intend to expand the program to improve quality of care for HCV
      patients in dialysis center. We propose active involvement of dialysis clinical staff
      including nephrologist, to increase HCV screening rate, promote timely diagnosis and
      treatment of CHC in patient with end-stage renal disease.

      This study is being conducted to evaluate real-world effectiveness of HCV DAA therapy in CHC
      hemodialysis patients when the DAA-treatment is managed and monitored by the clinical staff
      of hemodialysis center.

      Primary objective: To determine sustained virologic response (SVR) rates attained with
      open-label Zepatier administered through hemodialysis center under the supervision of a
      nephrologist in chronic hepatitis C infected (CHC) patient currently on hemodialysis.

      Secondary objective:

        1. To estimate prevalence of HCV infection, severity of fibrosis (using non-invasive
           measures), and HCV detection rate in patients with End stage renal disease on
           hemodialysis.

        2. To calculate the average treatment-lag time (time from HCV diagnosis to submission of
           treatment approval).
This study is being conducted to evaluate real-world effectiveness of HCV DAA therapy in CHC
      hemodialysis patients when the DAA-treatment is managed and monitored by the nephrologist of
      hemodialysis center.

      Hepatitis C virus (HCV) infects an estimated 185 million individuals worldwide (1) and 3.4
      million to 4.4 million people in the United States.(2) Approximately 80% of acutely infected
      HCV patients progress to chronic infection, 20% of whom develop cirrhosis within 25 years,
      with 25% of patients with cirrhosis developing hepatocellular carcinoma and/or decompensated
      liver disease.(3) Hepatitis C virus is the primary cause of liver transplantation in the
      United States.(4) There are 6 known genotypes of HCV. The most common genotypes in the United
      States are genotype 1 (subtypes 1a and 1b), 2, and 3, which together comprise 97% of all
      infections.(5) Since the discovery of HCV in 1989 (6) strategies to cure the infection have
      evolved dramatically. A cure is defined as a sustained virologic response (SVR) and consists
      of undetectable levels of plasma HCV RNA 12 or 24 weeks after therapy completion.(7)
      Treatment of HCV has evolved rapidly and has led to improved rates of SVR.

      Although these highly effective therapies for hepatitis C virus (HCV) infection have
      revolutionized treatment, only a few patients are able to receive treatment.(8) Barriers
      arising at multiple levels, from diagnosis to specialist referral, that still need to be
      overcome to move toward disease eradication.(9) In chronic kidney disease (CKD) patients, the
      prevalence of HCV infection is higher than in the general population. Testing for HCV in
      hemodialysis patients should be repeated every 6 months.(10) The national study on
      dialysis-associated diseases was published in 2002 and represents the infection statistics
      from dialysis center nationwide.(11) The overall estimated prevalence of HCV antibody in this
      study was 7.8%.

      In addition, patients with impaired kidney function have limited therapeutic options. The US
      Food and Drug Administration (FDA) recently approved Elbasvir/Grazopevir for treatment of
      genotype 1 and 4 infection in CKD patients including those on hemodialysis.

      At our institution, the Multidisciplinary Approach to the Treatment of Chronic Hepatitis C
      (MATCH) Initiative is a program which was first implemented to increase screening, diagnosis
      and treatment of HCV by actively incorporating primary care providers (PCP) at every step of
      the HCV care process. Following implementation of MATCH, early data indicates, marked
      increase in screening high risk and baby-boomer cohorts, as well as safe and effective
      treatment of HCV cases at the primary provider setting. The initiative proved that active
      participation of PCPs in the care of HCV reduced the treatment lag by 71% compared to
      traditional care of referring HCV cases to specialized care (Gastroenterology or Hepatology)
      while keeping similar SVR. (13) We intend to expand the program to improve quality of care
      for HCV patients in dialysis center. We propose active involvement of dialysis clinical staff
      including nephrologist, to increase HCV screening rate, promote timely diagnosis and
      treatment of CHC in patient with end-stage renal disease.

      Rationale of the study- We will perform a phase IV study to prove real world effectiveness of
      Zepatier in successful treatment of CHC in patients on chronic hemodialysis at hemodialysis
      centers, when administered under the supervision of a nephrologist. The study will be
      conducted in the selected collaborative hemodialysis centers.

      Zepatier Open-label Zepatier (grazoprevir 100 mg and elbasvir 50 mg) will be administered in
      this study.(14, 15) Zepatier is a fixed-dose combination tablet without ribavirin. GZR is an
      HCV NS3/4a inhibitor while EBR is an HCV NS5A inhibitor. Both grazoprevir and elbasvir are
      direct-acting antivirals, which together form an effective therapy for HCV and reduce the
      likelihood and effects of long-term liver-related HCV complications.

      Zepatier has been evaluated globally in multiple phase I, II, and III trials to treat HCV.
      (14, 15) Randomized, placebo-controlled trials have been carried out, which led to FDA
      approval for Zepatier as a treatment for genotype 1 and 4 HCV.

      As of July 1, 2015, a diverse population of over 1000 HCV patients has been exposed to
      Zepatier either as a single agent or in combination with ribavirin or sofosbuvir in phase
      I/II/III studies. Zepatier has been generally well tolerated at doses of 50-100 mg GZR and 50
      mg EBR orally once daily. It has been comparably effective across all subgroups it has been
      tested in, including non-cirrhotic and/or treatment-naïve subjects. (14, 15) Headaches,
      fatigue, and nausea represent the most common adverse drug reactions with Zepatier.3,4 Other
      drug-related adverse events have included arthralgia, insomnia, diarrhea, dizziness, pyrexia,
      and asthenia. (14, 15) Drug-related serious adverse events are uncommon, but include allergic
      reactions, possible adverse interactions with other medications, or elevated liver enzymes.
      In past Zepatier trials, the majority of the adverse events were reversible. These adverse
      events are usually mild or moderate events.

      The dosage in our study (100/50 mg daily) is a commonly attainable dose in clinical practice.
      Zepatier has shown to be safe for subjects with chronic kidney disease or who are on
      hemodialysis. Less than 1% of Zepatier is excreted renally. In Merck's C-SURFER, a phase 1
      randomized, controlled Zepatier trial, subjects with advanced kidney disease tolerated the
      drug well for the required 12 weeks without dose adjustments. (16) Zepatier trials have
      demonstrated a 94-100% success rate achieving HCV RNA levels of <15 IU/ml after 12 weeks of
      treatment (SVR-12) among genotype 1 HCV patients. (14, 15) This is a prospective cohort phase
      IV study using multidisciplinary approach for the treatment of hepatitis C in hemodialysis
      patients. Hemodialysis centers will be used to deliver all HCV related care.

      The study will be conducted in the selected collaborative hemodialysis centers in
      Philadelphia. In addition to the standard of care (SOC), all subjects with CHC will be
      evaluated for HCV DAA therapy: review of clinical records, assessment of the degree of liver
      fibrosis using FibroScan, baseline HCV virological tests, HIV and HBV screening, etc.
      Baseline and follow-up laboratory tests and FibroScan imaging will be performed at the
      Einstein lab or an alternative laboratory if requested by the patient. Baseline clinical
      evaluation and follow up focused H/P will be done by the nephrologist at the dialysis unit..
      The study coordinator is a MATCH-D navigator and is responsible for compiling supporting
      documents for HCV DAA treatment request and fax it to a designated fax number (to mimic
      faxing to the payers in real world scenario). Local specialty pharmacy pharmacist (also a
      part of the MATCH-D group) will be responsible for providing hepatitis C treatment education
      to approved patients, ensure delivery of DAA therapy and monitoring for any drug related
      adverse events.

      MATCH-D group will comprise of a study coordinator, study investigators, nephrologist,
      specialty pharmacy pharmacist, and dialysis unit . The group will meet weekly to review cases
      and provide recommendations on diagnosis, DAA selection and assist with HCV treatment This
      study will be divided to 3 phases.

        1. Training study team, dialysis center clinical staff (Quarterly refresher)

        2. Identifying hepatitis C patient and evaluation for treatment

        3. Treatment and follow up Phase 1: Training study team and dialysis center clinical staff
           education All collaborative hemodialysis centers coordinator and the study team will be
           educated for HCV screening, work-up, treatment and study protocol in the first month of
           study. There will be refresher course every 3 months.

      Phase 2: Identifying hepatitis C patient and evaluation for treatment

        1. Patient Screening a. Every dialysis patient will be offered HCV screening every 6 months
           as standard of care.

           b. HCV Ab with reflex HCV viral load will be ordered.

        2. Patient Identification

             1. Patients will be assessed for positive HCV Ab and detectable viral load.

             2. Nephrologist will notifythe patient with the results.

             3. Nephrologist will have the patient complete and sign HIPAA form.

             4. Nephrologist will email patient information to the study coordinator.

             5. Study coordinator is expected to keep composite record (including the above
                results) of all identified patients until enrollment. This record will be utilized
                at the Multidisciplinary Meeting.

             6. Informed consent will be obtained by the study coordinator.

             7. Basic demographic information will be collected.

        3. Patient evaluation for treatment

             1. Complete blood work and FibroScan imaging will be conducted at Einstein lab or an
                alternative laboratory if requested by the patient.

             2. Study coordinator is expected to ensure patients have all testing completed.

             3. Study coordinator will ensure all patients are tested for FibroScan imaging using
                the portable FibroScan® 530 Compact system. .

      This trial will enroll approximately 71 compensated cirrhotic and non-cirrhotic, Genotype 1
      and 4, HCV patients who are currently on hemodialysis. Non-invasive test will be used to
      determine the presence or absence of cirrhosis. All excluded CHC patients will receive
      standard of care. Patients who have decompensated cirrhosis or hepatoma will be referred to
      the hepatology clinic and receive care by the hepatologist.

      Study visits There will be 4 study visits in our study. Subjects may be asked to come early
      before dialysis session to have physical examination or Fibroscan.

      Screening and Informed consent

      During screening period, the following procedures and activities will be performed at
      hemodialysis center after the informed consent is signed:

        -  Review medical history and physical examination

        -  Review medication list

        -  Review laboratory data Baseline study • First laboratory tests will be performed at the
           Einstein lab or an alternative laboratory if requested by the patientand include: • CBC,
           CMP, PT/INR • HCV PCR Viral load

             -  HCV PCR genotype

             -  HCV NS5A RAV testing

             -  HBV screening: HBsAg, HBcAb

             -  HIV 1 / 2 Ab screening

             -  FibroScan

             -  Women of childbearing potential will have a pregnancy test at screening visit.
                Phase 3: Treatment and follow up 1. Treatment a. MATCH-D group will review and
                discuss identified CHC patients and determine those appropriate for DAA therapy
                through the dialysis center, and those who require referral to Liver Center based
                on work-up (e.g. decompensated cirrhosis).

                i. Patients appropriate for dialysis center treatment and agreeable to treatment
                will be enrolled in study.

                b. Meeting to occur weekly c. Study coordinator will notify the nephrologist, who
                saw patient, by email of the meeting decision. Subsequently, the nephrologist
                should notify patient of the decision and a) refer to hepatology if needed or b)
                explain need for treatment.

                d. Prescription along with pertinent information (e.g. lab results, fibrosis stage,
                etc.) will be compiled and sent to local specialty pharmacy by the study
                coordinator for all enrolled patients.

                e. Specialty pharmacy will:

                  1. Provide education to patients about prescribed treatment.

                  2. Identify potential drug interactions and notify team.

                  3. Oversee delivery of medications. Provide refill reminders to patients or
                     dialysis center staff.

                  4. Monitor medication adherence.

                  5. Keep "database" that is accessible to study coordinator and MATCH-D study
                     group Specialty pharmacy will be the investigational pharmacy who is
                     expertised in HCV care.

      Initiation treatment with Zepatier All subjects will be provided with a 28-day supply of the
      study drug and instructed to begin treatment once all tests are done. The study coordinator
      will call the patient to ensure treatment has begun for HCV with Zepatier.

      As with any scientific protocol, safety will be considered before treating the patients. The
      MATCH-D team will evaluate the patient's overall condition and make a judgment on whether
      initiating treatment is safe.

      Zepatier for 12 weeks or 16 weeks ± Ribavirin will be used to treat HCV genotype 1, 4 in our
      patients and will be supplied by Merck & Co.Inc.

      Statistical Methods The data will be collected using an Excel spreadsheet and analyzed with
      Stata 14.0 (Statacorp., College Town, TX). Descriptive statistics will be used to summarize
      the demographic characteristics. Screening rates, treatment rates, and treatment lag (time
      from detection to treatment submission) will be calculated. Categorical variables will be
      compared using chi square or fischer's exact test whereas continuous variables will be
      compared using student's t-test. SVR rates will also be compared with historical controls. P
      value of less than 0.05 will be considered statistically significant.

      Power/Sample Size:

      Power of 0.8 with a p-value of 0.05 were used a priori for sample size calculation. As was
      shown in C-SURFER trial recently, SVR of 99% was attained in chronic kidney disease patients
      including those on dialysis. Accepting a non-inferiority margin of 5% and similar expected
      SVR in our cohort, the sample size was calculated to be 71 patients.

      Potential Benefits The subjects will get clinical benefits as the HCV treatment can prevent
      cirrhosis and hepatocellular carcinoma in the future. This study also has a potential to
      speed up treatment evaluation and the subjects may get the treatment faster.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: HCV treatment-lag time
time frame: 12 weeks
description: To determine the average treatment-lag time (time from HCV diagnosis to submission of treatment approval) of HCV treatment delivered through hemodialysis centers by nephrologists compared to standard of care via traditional gastroenterology or hepatology centers.
measure: Prevalence rates
time frame: 12 weeks
description: To estimate prevalence of HCV infection, severity of fibrosis (using non-invasive measures), and HCV detection rate in patients with End stage renal disease on hemodialysis.
measure: Sustained virologic response (SVR) rates
time frame: 6 months
description: 2. To determine sustained virologic response (SVR) rates of open-label Zepatier in chronic hepatitis C infected (CHC) patient who are currently on hemodialysis.
arm group label: Zepatier treatment
arm group type: Experimental
description: Open-label Zepatier (grazoprevir 100 mg and elbasvir 50 mg) will be administered in this study. Daily treatment of Zepatier for a 12-week duration will be administered.
intervention type: Drug
intervention name: Zepatier
description: Patients screened as HCV positive will receive Zepatier for 12 weeks.
arm group label: Zepatier treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Eyob Feyssa, MD
role: Principal Investigator
affiliation: Albert Einstein Healthcare Network
last name: Eyob Feyssa, MD
role: Study Chair
affiliation: Albert Einstein Healthcare Network
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PMID: 21745274
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PMID: 11584380
citation: Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010 Feb;138(2):513-21, 521.e1-6. doi: 10.1053/j.gastro.2009.09.067. Epub 2009 Oct 25.
PMID: 19861128
citation: Delwart E, Slikas E, Stramer SL, Kamel H, Kessler D, Krysztof D, Tobler LH, Carrick DM, Steele W, Todd D, Wright DJ, Kleinman SH, Busch MP; NHLBI-REDS-II Study Group. Genetic diversity of recently acquired and prevalent HIV, hepatitis B virus, and hepatitis C virus infections in US blood donors. J Infect Dis. 2012 Mar 15;205(6):875-85. doi: 10.1093/infdis/jir862. Epub 2012 Jan 31.
PMID: 22293432
citation: Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359-62. doi: 10.1126/science.2523562.
PMID: 2523562
citation: Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, Abergel A, Pessoa MG, Lin A, Tietz A, Connell EV, Diago M. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology. 2010 Nov;139(5):1593-601. doi: 10.1053/j.gastro.2010.07.009. Epub 2010 Jul 14.
PMID: 20637202
citation: McGowan CE, Fried MW. Barriers to hepatitis C treatment. Liver Int. 2012 Feb;32 Suppl 1(0 1):151-6. doi: 10.1111/j.1478-3231.2011.02706.x.
PMID: 22212587
citation: Konerman MA, Lok AS. Hepatitis C Treatment and Barriers to Eradication. Clin Transl Gastroenterol. 2016 Sep 22;7(9):e193. doi: 10.1038/ctg.2016.50.
PMID: 27657495
citation: Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl. 2008 Apr;(109):S1-99. doi: 10.1038/ki.2008.81. No abstract available.
PMID: 18382440
citation: Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005 Jan-Feb;18(1):52-61. doi: 10.1111/j.1525-139X.2005.18108.x.
PMID: 15663766
citation: AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015 Sep;62(3):932-54. doi: 10.1002/hep.27950. Epub 2015 Aug 4. No abstract available.
PMID: 26111063
citation: Sandhu N, Mulki R, Tosounian S, Wheeler D, Feyssa E, Baumann A. Multidisciplinary Approach to the Treatment of Chronic Hepatitis C: The MATCH Initiative AASLD Abstract presentation. 2017.
citation: Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
PMID: 25895428
citation: Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.
PMID: 25909356
citation: Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5. Erratum In: Lancet. 2015 Nov 7;386(10006):1824.
PMID: 26456905
citation: Merck Sharp & Dohme Corporation (January 2016). ZEPATIER™ tablets. Highlights of Prescribing Information. 2016.
citation: Merck Sharp & Dohme Corporation (July 2015). Elbasvir (MK-8742). Investigator's Brochure (8th Ed.).2015.
citation: Merck Sharp & Dohme Corporation (July 2015). Grazoprevir (MK-5172). Investigator's Brochure (10th Ed.). 2015.
responsible party type: Principal Investigator
investigator affiliation: Albert Einstein Healthcare Network
investigator full name: Eyob Feyssa
investigator title: MD
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Elbasvir-grazoprevir drug combination
sharing ipd: No