The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

• Status: Active, not recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, pilot trial to test the safety and efficacy of transplantation of kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney transplant waitlist. Treatment and prophylaxis will be administered using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amit D Tevar, MD; Amit Tevar
• Collaborator: University of Pittsburgh Medical Center
• Treatments: Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir

Criteria

Inclusion criteria (recipients):

1. Patients with end-stage renal disease listed for kidney transplantation at UPMC.

2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min

3. Age ≥ 18

4. No available living kidney donor

5. Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time

6. Have panel reactive antibody level of <98%

7. No obvious contraindication to kidney transplant

8. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation

9. Able to provide informed consent

10. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

1. HIV positive

2. HCVAb or HCV RNA positive

3. Presence of behavioral risk factors for contracting HCV other than being on hemodialysis. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.

4. Hepatitis B surface antigen positive

5. History of liver cirrhosis

6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months

7. History of atrial fibrillation requiring the use of amiodarone over the past 12m

8. Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team

9. Receipt of prior organ transplant

10. Waitlisted for a multi-organ transplant

11. Pregnant women

12. Known allergy to sofosbuvir/velpatasvir

13. Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Inclusion criteria (donors):

1. HCV antibody positive

2. HCV NAT negative or positive

3. Kidney donor profile index (KDPI) score <85

Exclusion criteria (donors):

1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)

2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)

3. Known ongoing therapy for HCV