Ignite Creation Date:
2024-05-06 @ 12:12 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03702218
Status:
WITHDRAWN
Last Update Posted:
2023-05-06
First Post:
2018-10-08
Brief Title:
Hepatitis C Positive Donor Into Hepatitis C Negative Recipients
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
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
Status:
WITHDRAWN
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
never started
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 andor 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
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 andor 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
Detailed Description:
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 1000 IUmL 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 ie 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
HCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint guidelines after giving consideration to the transplanted organ renal function and HCV genotype All regimens exclude administration of ribavirin
Therapy will be initiated as soon as possible pending initiation of oral intake and insurance approval following organ transplantation
DAAs will be prescribed after which medications will then be delivered to the patients home or to the bedside
If therapy is delayed beyond the 4-week appointment with Hepatology post-transplant a protocol to monitor for infection new-onset diabetes mellitus glomerulonephritis and severe cholestatic hepatitis will be implemented This protocol will include weekly blood work to include CBC with differential hepatic function panel basic metabolic panel and coagulation studies
Liver Transplant
Combinations of choice
Mavyret glecaprevirpibrentasvir - Genotype 1-6
Harvoni ledipasvirsofosbuvir Ribavirin - Genotypes 1 4 5 6 GFR30
Epclusa sofosbuvirvelpatasvir Ribavirin - Genotypes 1-6 GFR30
Kidney Transplant
Combinations of choice
Mavyret glecaprevirpibrentasvir - genotype 1-6
Harvoni sofosbuvirledipasvir - genotype 1 4 GFR30 HCV Follow-Up HCV RNA complete blood count CBC and liver biochemistries will be checked 4 weeks 8 weeks and 12 weeks after starting therapy In patients previously exposed to HBV HBV surface antigen will be followed qualitatively at the same intervals
HCV RNA will also be checked 12 weeks after completion of therapy to define cure or sustained virologic response As part of long-term follow-up HCV RNA will be checked annually at routine post-transplant visits
If SVR is not achieved a second and if needed third antiviral regimen will be provided to the participant at no cost
Transplant Post-Operative Immunosuppression Follow Up All will be as per UMMC standard of care Unless otherwise contraindicated tacrolimus immune suppression will be favored due to drug-drug interactions associated with DATs and cyclosporine
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 1000 IUmL 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 ie 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
HCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint guidelines after giving consideration to the transplanted organ renal function and HCV genotype All regimens exclude administration of ribavirin
Therapy will be initiated as soon as possible pending initiation of oral intake and insurance approval following organ transplantation
DAAs will be prescribed after which medications will then be delivered to the patients home or to the bedside
If therapy is delayed beyond the 4-week appointment with Hepatology post-transplant a protocol to monitor for infection new-onset diabetes mellitus glomerulonephritis and severe cholestatic hepatitis will be implemented This protocol will include weekly blood work to include CBC with differential hepatic function panel basic metabolic panel and coagulation studies
Liver Transplant
Combinations of choice
Mavyret glecaprevirpibrentasvir - Genotype 1-6
Harvoni ledipasvirsofosbuvir Ribavirin - Genotypes 1 4 5 6 GFR30
Epclusa sofosbuvirvelpatasvir Ribavirin - Genotypes 1-6 GFR30
Kidney Transplant
Combinations of choice
Mavyret glecaprevirpibrentasvir - genotype 1-6
Harvoni sofosbuvirledipasvir - genotype 1 4 GFR30 HCV Follow-Up HCV RNA complete blood count CBC and liver biochemistries will be checked 4 weeks 8 weeks and 12 weeks after starting therapy In patients previously exposed to HBV HBV surface antigen will be followed qualitatively at the same intervals
HCV RNA will also be checked 12 weeks after completion of therapy to define cure or sustained virologic response As part of long-term follow-up HCV RNA will be checked annually at routine post-transplant visits
If SVR is not achieved a second and if needed third antiviral regimen will be provided to the participant at no cost
Transplant Post-Operative Immunosuppression Follow Up All will be as per UMMC standard of care Unless otherwise contraindicated tacrolimus immune suppression will be favored due to drug-drug interactions associated with DATs and cyclosporine
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None