Clinical trial NCT03365635
Conditions: Hepatitis C Hemodialysis Nosocomial Infection
Sponsor: University of Pennsylvania
Start date: 2019-09-22; Completion date: 2020-09-01
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a study to define strategies for Nephrologists to directly supervise and apply direct acting antivirals to cure hepatitis C in hemodialysis patients. Strategies will include identification of candidate patients, application for insurance approval, specifics of direct acting antiviral therapy (Zepatier with or without ribavirin) and laboratory monitoring during and after therapy.

Detailed description:
Background - Hepatitis C (HCV) is common in hemodialysis (HD) patients with reported prevalences of 25%, By 2020, predicted 775,000 hemodialysis patients in the US, of whom 109,000 will have HCV. Hepatitis C is associated with increased mortality in HD patients, decreased kidney allograft survival, and a source of nosocomial infection in hemodialysis units. Currently drugs to cure HCV - direct acting antivirals (DAA) which can be safely given to HD patients are now available. A significant portion of the medical care provided to HD patients is by Nephrologists and HD staff.

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

Arms: arm 1: Genotype 1a - treatment naive without NS5A polymorphism - Drug Intervention : Oral administration Elbasvir (50mg)/Grazoprevir (100mg) one tablet per day for 12 weeks arm 2: Genotype 1a - treatment naiive with NS5A polymorphism - Oral administration of Elbasvir/Grazoprevir one tablet daily and ribavirin (200 mg) daily for 16 weeks weeks arm 3: Genotype 1b-treatment naive - Oral administration of Elbasvir/Grazoprevir one daily for 12 weeks arm 4: 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 arm 5: (e) Genotype 4 - treatment naive - oral administration of Elbasvir/Grazoprevir one daily for 12 weeks arm 6: Genotype 4 -prior treatment - oral administration of Elbasvir/Grazoprevir and ribavirin each once per day for 16 weeks
Interventions: intervention 1: Elbasvir 50 MG / Grazoprevir 100 MG [Zepatier]
Intervention descriptions: intervention 1: Same as described in arm description

Protocol documents:
ICF_002.pdf: 
Protocol Title: Real World Administration of Zepatier (Grazoprevir plus Elbasvir) in 
Chronic Hemodialysis Patients with Hepatitis C Infection. Strategies 
for Identification of Candidate Hemodialysis Patients, Obtainment 
of Insurance Approval, Treatment Guidelines, and Laboratory and 
Clinical Monitoring During Therapy Directed to Nephrologists 
NCT Number: 03365635 
IRB Approval Date: August 13, 2018 
Document: Informed Consent Form
August 18, 2021 























Prot_000.pdf: 
Protocol Title: Real World Administration of Zepatier (Grazoprevir plus Elbasvir) in 
Chronic Hemodialysis Patients with Hepatitis C Infection. Strategies 
for Identification of Candidate Hemodialysis Patients, Obtainment 
of Insurance Approval, Treatment Guidelines, and Laboratory and 
Clinical Monitoring During Therapy Directed to Nephrologists 
NCT Number: 03365635 
IRB Approval Date: August 13, 2018 
Document: Protocol August 18, 2021 

































































































SAP_001.pdf: 
Protocol Title: Real World Administration of Zepatier (Grazoprevir plus Elbasvir) in 
Chronic Hemodialysis Patients with Hepatitis C Infection. Strategies 
for Identification of Candidate Hemodialysis Patients, Obtainment 
of Insurance Approval, Treatment Guidelines, and Laboratory and 
Clinical Monitoring During Therapy Directed to Nephrologists 
NCT Number: 03365635 
IRB Approval Date: August 13, 2018 
Document: Statistical Analysis Plan  August 18, 2021