Clinical trial NCT03623568: Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant
Official title: Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Kidney Failure
Kidney Diseases
Hepatitis C
Keywords: CKD
HCV
Hepatitis C
Transplant
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2018-08-09
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Undetectable HCV RNA in blood
timeFrame: 12 weeks post treatment
Secondary outcomes:
measure: Safety (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation)
timeFrame: 12 weeks post treatment
measure: Tolerability (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation
timeFrame: 12 Weeks post treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Raymond T Chung, MD
role: PRINCIPAL_INVESTIGATOR
References: