Hepatitis C, Kidney Diseases, Kidney Failure
Conditions
Keywords
CKD, HCV, Hepatitis C, Transplant
Brief summary
This is a proof of concept, single center study for the donation of HCV-positive kidney to HCV negative recipient patients, with preemptive, interventional treatment with 12 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.
Detailed description
The goal of this study is to determine if preoperative dosing and sustained administration of pan-genotypic DAA therapy after kidney transplantation prevents the transmission of hepatitis C virus (HCV) infection from an HCV positive donor kidney to an HCV naïve recipient.
Interventions
DRUGglecaprevir/pibrentasvir tablets
12 weeks of treatment with Mavyret
Sponsors
Raymond T. Chung, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Met MGH transplant center criteria and already listed for kidney transplant * No available living kidney donor * Has ≤ 730 days (two years) of accrued transplant waiting time if blood type A and ≤ 1095 days of accrued transplant waiting time if blood type B or O. * On chronic hemodialysis or peritoneal dialysis or has a glomerular filtration rate \<15mL/min/1.73m2 at the time of screening * Must agree to birth control. Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy and at least one barrier method * Weigh at least 50kg * Serum ALT within normal limits with no history of liver disease * Able to sign informed consent
Exclusion criteria
* AB blood type * BMI \> 35 * Any liver disease in recipient * Pregnant or nursing (lactating) women * Known allergy or intolerance to tacrolimus that would require administration of cyclosporine rather than tacrolimus given the known drug-drug interaction between cyclosporine and Mavyret * Cardiomyopathy (LV ejection fraction \< 50%) * Albumin \< 3g/dl or platelet count \< 75 x 103/mL * Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist * Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist * HCV RNA positive * Hepatitis B surface antigen positive * Any known liver disease or elevated liver transaminases * Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as assessed by the transplant nephrologist and/or the investigator team * Any contra-indication to kidney transplantation per MGH center protocol * Patients on the following medications who cannot stop therapy: carbamazepine, rifampin, St. John's wort, and ethinyl estradiol-containing oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable HCV RNA in blood | 12 weeks post treatment | Negative HCV viral RNA at 12 weeks after the last dose of treatment as determined by blood test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation) | 12 weeks post treatment | Safety of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient. |
| Tolerability (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation | 12 Weeks post treatment | Tolerability of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient. |
Countries
United States
Outcome results
None listed