Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients
Condition: Kidney Transplant; Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Direct acting Anti-Viral Therapy using Epclusa or Zepatier
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Epclusa, Zepatier
Intervention MeSH terms: Sofosbuvir-velpatasvir drug combination; Elbasvir-grazoprevir drug combination; Antiviral Agents
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment