An Open-label Pilot Study to Determine the Safety and Efficacy of Hepatitis C Uninfected Recipients of Renal and Liver Transplants From a Currently Infected or Previously Infected Hepatitis C Donor
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- SVR after receiving an organ from a donor previously exposed to Hepatitis C after treatment direct-acting antiviral drugs.
研究概览
简要总结
Despite many efforts to increase the size of the donor pool, there is a large and growing disparity between the number of donor kidneys and livers available for transplantation and the number of patients on the transplant waiting list. New donor pools are needed to satisfy the lack of available donor organs, along with expanded criteria for the existing donor pools.
A new standard of care now exists at most local and regional transplant centers. This new standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure rates and minimal side effect profiles. The efficacy and tolerability of these medications has allowed the expansion of the available donor pool by making HCV antibody positive non viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool may decrease time on the waiting list and improve quality of life and survival while waiting for organ transplantation.
Study Aim:
We propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ donors for transplantation into HCV negative recipients.
The primary purpose of the clinical protocol is to:
Collect prospective standard of care laboratory data on the results of these interventions
详细描述
Once the donor is accepted for transplantation and the recipient enrolled in the innovative clinical practice, donor HCV Ab status will be requested to initiate HCV RNA viral load testing.
Donor data will be recorded as per our standard practice and as mandated by UNOS. Our University of Maryland Medical Center team will be responsible for the donor operation as per standard of care.
Hep C Ab + NAT - Donor to Naïve Recipient This group will be monitored as illustrated in figure 1. Hep C Ab+ NAT+ Donor to Naïve Recipient HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.
Due to risk of HBV reactivation with DAA therapy, Hepatitis B surface antigen, surface antibody and core antibody status will be determined prior to HCV therapy. In patients with a prior exposure to HBV (i.e. positive HBV core antibody), Hepatitis B surface antigen levels will be monitored throughout therapy.
All patients will be seen in the Hepatology clinic within 4 weeks of transplant to establish care and follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •RECIPIENT INCLUSION CRITERIA
- •Patients undergoing solid organ transplantation, including liver, kidney, and simultaneous liver-kidney who are not chronically infected with HCV
- •No evident contraindication for organ transplantation
- •HCV RNA negative (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
- •Age 18-75 years at the time of transplantation
- •Signed Informed Consent Form
- •No identified living organ donor
- •Able to travel to the University of Maryland for routine post-transplant and HCV follow-up visits
- •Men and women must agree to use at least one barrier method to prevent any secretion exchange
- •No active illicit drug use
- •DONOR INCLUSION CRITERIA
- •Qualitative HCV nucleic acid test (NAT) positive and/or Hepatitis C antibody positive HCV donors offered to the University of Maryland.
排除标准
- •RECIPIENT EXCLUSION CRITERIA
- •History of prior solid organ transplantation
- •HIV infection
- •HBV surface antigen or DNA positive. Organs from HCV positive donors who are also Hepatitis B core antibody positive (hepatitis B surface antigen negative) can be used. These patients will however need to undergo prophylaxis for HBV according to their respective organ specific criteria and during treatment for hepatitis C due to the increased risk of reactivation of hepatitis B with DAA therapy
- •Waitlisted for a multi-organ transplant (with the exception of simultaneous liver-kidney transplant)
- •HCV RNA positive (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
- •Prior direct-acting antiviral (DAA) treatment for HCV. Patients previously treated with interferon-based regimens may be included.
- •DONOR EXCLUSION CRITERIA
- •Every donor that is considered unsuitable by the transplant surgeon for any reason.
- •Hepatocellular carcinoma
- •HIV infection
- •Use of HCV positive livers to be determined according to current existing criteria
研究组 & 干预措施
Hep C Ab + NAT - Donor to Naïve Recipient
HCV Ab and HCV NAT testing at 3 days, week 1, week 2 and monthly for 3 months, at 6 months and 1 year. In approximately 16% of the patients, active hepatis C infection will ensue. For these patients, treatment is as follows.
Liver Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
- Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
- Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30
Kidney Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
- Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30
干预措施: Direct Acting Antivirals (Drug)
Hep C Ab+ NAT+ Donor to Naïve Recipient
HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.
Liver Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
- Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
- Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30
Kidney Transplant:
• Combinations of choice:
- Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
- Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30
干预措施: Direct Acting Antivirals (Drug)
Hep C Ab- NAT - Donor to Naïve Recipient
Current standard of care for donor recipient infectious disease matching. No treatment necessary
干预措施: Direct Acting Antivirals (Drug)
结局指标
主要结局
SVR after receiving an organ from a donor previously exposed to Hepatitis C after treatment direct-acting antiviral drugs.
时间窗: 12 months
To improve access to transplantation with use of HCV-non viremic and HCV-viremic organs in HCV negative patients
次要结局
未报告次要终点