Administration of Zepatier (Grazoprevir Plus Elbasvir) in Chronic Hemodialysis (HD) Patients With Hepatitis C
NCT ID: NCT03365635
Last Updated: 2021-12-15
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
6 participants
INTERVENTIONAL
2019-09-22
2020-09-01
Brief Summary
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Detailed Description
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Goals of Protocol - 1. Provide guidelines for implementation and monitoring of DAA therapy in HD patients with HCV 2. Provide Nephrologists strategies for identification of candidate HD patients, obtainment of third party approval for DAA payment, specific drug dosing protocols based on genome type of HCV, and laboratory and clinical monitoring during DDA therapy. 3, By reducing the pool of HCV patients in a HD Unit, the risk of nosocomial transmission of HCV t o other patients and staff will be reduced
Study Design - an interventional, prospective, non-randomized, non-blinded trial to evaluate real world strategies to identify and treat HCV infected patients with Zepatier
Study Procedures 1. Patients who meet inclusion criteria without exclusion criteria be assigned treatment with Zepatier with or without Ribavirin according to following schedule: (a) Genotype 1a - treatment naive without NS5A polymorphism - Zepatier one tablet (100 mg grazoprevir and 50 mg elbasvir) per day for 12 weeks (b) Genotype 1a - treatment naiive with NS5A polymorphism - Zepatier one tablet daily and ribavirin (200 mg) daily for 16 weeks (c) Genotype 1b-treatment naive - Zepatier one daily for 12 weeks (d) Genotype 1a or 1b - prior treatment with INF or HCV NS3/4A protease inhibitor - Zepatier and ribavirin each once daily for 12 weeks (e) Genotype 4 - treatment naive - Zepatier one daily for 12 weeks (f)Genotype 4 -prior treatment - Zepatier and ribavirin each once per day for 16 weeks
Baseline/Screening Testing: 1. HCV genotype testing 2. HCV viral RNA load 3. Liver function tests 4, Protime, Partial Thromboplastin time 5. HIV - if positive, then determine viral RNA and CD4 and T cell count 6. Liver biopsy (within 24 mo of treatment) or Fibroscan within 12 mo of treatment 7. Hepatitis BsAg 8. For patients with HCV genotype 1a, test fro NS5A mutation
Treatment of HIV/HCV co-infected patients will be done in collaboration with the HIV treating physician to determine if any adjustments in the HIV drug regimen will be required
Testing/Evaluations during Active DAA Treatment - 1. LFT and RNA HCV viral load at week 4, 8, and 12. For patients on 16 weeks of treatment, LFT at week 16 as well 2. For patients on combination Zepatier and ribavirin, hemoglobin monitoring every week during treatment 3. Clinical pharmacology evaluation for compliance and adverse events at week 4,8,and 12 (and week 16 for patients on 16 week treatment)
Testing/Evaluation Post DAA Treament - 1, RNA viral load at 12 weeks post treatment 2. Clinical Pharmacologoy evaluation 12 weeks post treatment for adverse events 3. patients who achieve sustained viral remission at 12 weeks will be identified in HD records as HCV ab positive but HCV viral load RNA negative
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Genotype 1a -Rx naive -no NS5A polymorph
Genotype 1a - treatment naive without NS5A polymorphism - Drug Intervention : Oral administration Elbasvir (50mg)/Grazoprevir (100mg) one tablet per day for 12 weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Genotype 1a, Rx naive + NS5A polymorph
Genotype 1a - treatment naiive with NS5A polymorphism - Oral administration of Elbasvir/Grazoprevir one tablet daily and ribavirin (200 mg) daily for 16 weeks weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Genotype 1b - Rx naive
Genotype 1b-treatment naive - Oral administration of Elbasvir/Grazoprevir one daily for 12 weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Genotype 1a/1b -prior INF or NS3/4A
Genotype 1a or 1b - prior treatment with INF or HCV NS3/4A protease inhibitor - oral administration of Elbasvir/Grazoprevir and ribavirin each once daily for 12 weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Genotype4 - treatment naive
(e) Genotype 4 - treatment naive - oral administration of Elbasvir/Grazoprevir one daily for 12 weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Genotype 4- prior treatment
Genotype 4 -prior treatment - oral administration of Elbasvir/Grazoprevir and ribavirin each once per day for 16 weeks
Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Interventions
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Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Same as described in arm description
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* \> age 18 years old
* Hepatitis C antibody positive and Hepatitis C RNA Quantification positive
* Hepatitis C genomes 1a, 1b, or 4
* Prior Interferon , ribavirin treatment failures , partial responders, or intolerance to these treatment allowed to enroll
* Not of reproductive potential - hemodialysis patients must have no menses for 12 months
* Males with partners of reproductive potential as along a 2 reliable forms of contraception are used simultaneously during treatment and for 6 months after completion of treatment
* Ability to understand the study procedures, alternative treatments available, risks of participating in the study, and voluntarily agree to participate
Exclusion Criteria
* Have moderate or severe hepatic disease - Child-Pugh B or C
* Have evidence of decompensated liver disease manifested by ascites, gastric or variceal bleeding, hepatic encephalopathy, or other signs/symptoms of advanced liver disease
* Co-administration of known heaptotoxic drugs including but not limited to : etofoxine, isoniazid, nitrofurantoin, phenytoin
* Use of strong CYP3A/P-gp inhibitors, organic acid transporting polypeptide 1B1/3 inhibitors, strong inducers of cytochrome 450 3A (CYP3A), efavirenz, or other drugs which may interact with elbasvir/grazoprevir as per package insert
* history of substance abuse with alcohol, intravenous drugs, psychotropics, narcotics, cocaine use within 1 year of screening for study
* history of any condition, pre-study lab abnormality, or ECG abnormality or history of any illness which in the opinion of the investigators might confound the results of the study or pose additional risks from the administration of elbasvir/grazoprevir
* Have evidence of history of chronic hepatitis not caused by HCV including but not limited to nonalcoholic steatohepatitis (NASH), drug induced hepatitis, and autoimmune hepatitis
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
University of Pennsylvania
OTHER
Responsible Party
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Michael Rudnick
Principle Investigator
Principal Investigators
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Michael R Rudnick, MD
Role: PRINCIPAL_INVESTIGATOR
University of Pennsylvania Health System
Locations
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Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
Countries
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References
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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.
Goodkin DA, Bieber B, Jadoul M, Martin P, Kanda E, Pisoni RL. Mortality, Hospitalization, and Quality of Life among Patients with Hepatitis C Infection on Hemodialysis. Clin J Am Soc Nephrol. 2017 Feb 7;12(2):287-297. doi: 10.2215/CJN.07940716. Epub 2016 Dec 1.
Zaki MSE. The effect of Hepatitis C Virus infection on cardiovascular complications in end stage kidney disease patients on regular hemodialysis. Electron Physician. 2017 Feb 25;9(2):3857-3861. doi: 10.19082/3857. eCollection 2017 Feb.
Jadoul M, Horsmans Y. Towards eradication of hepatitis C virus from dialysis units. Lancet. 2015 Oct 17;386(10003):1514-5. doi: 10.1016/S0140-6736(15)00381-5. Epub 2015 Oct 5. No abstract available.
Lo Re V. Extrahepatic Complications of Hepatitis C Virus Infection in HIV and the Impact of Successful Antiviral Treatment. Clin Infect Dis. 2017 Feb 15;64(4):498-500. doi: 10.1093/cid/ciw814. No abstract available.
Cacoub P, Desbois AC, Isnard-Bagnis C, Rocatello D, Ferri C. Hepatitis C virus infection and chronic kidney disease: Time for reappraisal. J Hepatol. 2016 Oct;65(1 Suppl):S82-S94. doi: 10.1016/j.jhep.2016.06.011.
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.
Rao AK, Luckman E, Wise ME, MacCannell T, Blythe D, Lin Y, Xia G, Drobeniuc J, Noble-Wang J, Arduino MJ, Thompson ND, Patel PR, Wilson LE. Outbreak of hepatitis C virus infections at an outpatient hemodialysis facility: the importance of infection control competencies. Nephrol Nurs J. 2013 Mar-Apr;40(2):101-10, 164; quiz 111.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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828322
Identifier Type: -
Identifier Source: org_study_id