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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03249194
Recruitment Status : Active, not recruiting
First Posted : August 15, 2017
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Tracking Information
First Submitted Date  ICMJE August 9, 2017
First Posted Date  ICMJE August 15, 2017
Last Update Posted Date March 8, 2019
Actual Study Start Date  ICMJE August 17, 2017
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2017)
  • Sustained Virologic Response (SVR) [ Time Frame: 12 weeks ]
    Among the patients who develop HCV viremia SVR rates with DAA will be measured
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03249194 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2017)
  • 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
  • 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
  • Liver Disease [ Time Frame: 1 year ]
    Among patients who develop HCV viremia liver disease progression will be measured using non-invasive panels like fibroscan
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients
Official Title  ICMJE Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients: A Trial of Ultra-short Duration Direct Acting Anti-viral Prophylaxis To Prevent Virus Transmission From Hepatitis C Viremic Donors To Hepatitis C Negative Kidney Transplant Recipients (DAPPER)
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.
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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Kidney Transplant
  • Hepatitis C
Intervention  ICMJE 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
Study Arms  ICMJE 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.

Intervention: Drug: Direct acting Anti-Viral Therapy using Epclusa or Zepatier
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 4, 2018)
25
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2017)
6
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03249194
Other Study ID Numbers  ICMJE HM20010320
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gaurav Gupta, MD Virginia Commonwealth University
PRS Account Virginia Commonwealth University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP