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Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients

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ClinicalTrials.gov Identifier: NCT03249194
Recruitment Status : Active, not recruiting
First Posted : August 15, 2017
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus (HCV) has changed the landscape of HCV therapy dramatically in the last several years with reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV positive patients including those who have received liver or kidney transplants. Since these new regimens do not include interferon and have already been studied in the post-liver and kidney transplant setting, they now offer a unique opportunity to expand the donor pool and improve the lives of those awaiting renal transplant. The address this gap in knowledge, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable risks and improved survivals compared with historical cohorts.

Condition or disease Intervention/treatment Phase
Kidney Transplant Hepatitis C Drug: Direct acting Anti-Viral Therapy using Epclusa or Zepatier Early Phase 1

Detailed Description:

Traditionally, HCV+ kidneys are not offered to HCV- patients on the waiting list. The primary concern with offering HCV+ kidneys to HCV- recipients is a risk of viral transmission. Although data about the long-term impact of HCV+ kidney transplantation in to HCV- recipients is unclear, there was a clear suggestion of an increased risk of liver disease in these patients based upon studies performed in the 1990s. Traditional therapy with Interferon could not be offered to these patients as it can lead of rejection if kidney transplant. It was recently reported that nearly 65% (out of a total 6546) of all HCV+ kidneys were discarded between the years 2005-2014. These kidneys were otherwise of excellent quality and could have benefitted more than 4000 patients with 12,000 plus years of graft life.

Since the recent FDA approval of Direct Acting Anti-virals (DAA), these drugs have now been shown to be safe and efficacious even in the setting of kidney transplant. They could offer a unique opportunity to expand the kidney donor pool. For this study, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV+ kidneys in disadvantaged and needy HCV- kidney recipients with acceptable risks and improved survivals compared with historical cohorts. This novel study will develop pilot data on the safety and efficacy of utilizing HCV+ kidneys in high-risk HCV- recipients in order to expand the donor pool and reduce the morbidity and mortality of hemodialysis.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients: A Novel Application of Direct-Acting Antiviral Drugs
Actual Study Start Date : August 17, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HCV+ Donor Kidney Recipient

All HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant.

Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks.

Drug: Direct acting Anti-Viral Therapy using Epclusa or Zepatier
All patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results
Other Name: Epclusa, Zepatier




Primary Outcome Measures :
  1. Sustained Virologic Response (SVR) [ Time Frame: 12 weeks ]
    Among the patients who develop HCV viremia SVR rates with DAA will be measured

  2. Graft and Patient Survival [ Time Frame: 1 year ]
    Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice


Secondary Outcome Measures :
  1. Sustained Virologic Response (SVR) Follow Up 1 [ Time Frame: 24 weeks ]
    Among the patients who develop HCV viremia SVR rates with DAA will be measured

  2. Sustained Virologic Response (SVR) Follow Up 2 [ Time Frame: 48 weeks ]
    Among the patients who develop HCV viremia SVR rates with DAA will be measured

  3. Liver Disease [ Time Frame: 1 year ]
    Among patients who develop HCV viremia liver disease progression will be measured using non-invasive panels like fibroscan



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • No evidence of HCV infection by HCV PCR (done at the time of the initial consent)
  • Age>60 yrs with an expected waiting time>2 years; or
  • Age<60 yrs with any one of the following risk factors: Diabetes, coronary artery disease, peripheral artery disease and/or cerebrovascular disease
  • Willingness to provide informed consent
  • Absence of a living donor.

Exclusion Criteria:

  • Estimated life expectancy of less than one year based on clinical judgment of the investigator
  • Prior liver or renal transplantation
  • Pregnant women
  • Incarcerated patients
  • Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
  • Unable or unwilling to return for follow-up visits

Donor Exclusion Criteria:

  • HBV sAg positive
  • HIV PCR or antibody positive
  • HCV RNA negative

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03249194


Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Gaurav Gupta, MD Virginia Commonwealth University

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT03249194     History of Changes
Other Study ID Numbers: HM20010320
First Posted: August 15, 2017    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Antiviral Agents
Elbasvir-grazoprevir drug combination
Sofosbuvir-velpatasvir drug combination
Anti-Infective Agents