None listed
Conditions
Brief summary
This is a prospective, cohort study aiming to determine the feasibility of transplanting HCV positive kidneys into HCV negative recipients. The study team will identify potentially eligible subjects from the renal transplant waiting list. The study will be explained to them by both renal and gastroenterology study team members. Adequate time will be given for all questions to be answered to the participants complete satisfaction. Once the informed consent form has been signed, the subjects eligibility will be confirmed. When a HCV positive kidney becomes available, the transplant will occur as per normal practice. As deemed clinically appropriate, as soon as possible after transplant the study subject will be commenced on a direct acting antiviral (DAA) treatment regimen of glecaprevir and pibrentasvir (g/p) for 12 weeks. The subjects normal, renal post-transplant inpatient and outpatient protocols will be followed. In addition, the subject will have follow-up with the Gastroenterology study team and additional blood samples will be taken to monitor HCV status and liver function. In particular, HCVRNA will be monitored until expected HCVRNA clearance at week 12.
Interventions
Patients will be eligible for this study if they are being wait-listed for renal transplant as part of standard practice and according to national guidelines for renal transplantation.
Patients identified as eligible (and on a wait list for renal transplant) will be considered for the study. Patients (potential recipients) who consent will be screened for Hepatitis C (HCV) infection by a serum HCV RNA PCR test (standard test) to exclude active hepatitis C infection prior to transplant.
HCV RN
Patients will be eligible for this study if they are being wait-listed for renal transplant as part of standard practice and according to national guidelines for renal transplantation. Patients identified as eligible (and on a wait list for renal transplant) will be considered for the study. Patients (potential recipients) who consent will be screened for Hepatitis C (HCV) infection by a serum HCV RNA PCR test (standard test) to exclude active hepatitis C infection prior to transplant. HCV RNA positive-kidneys will be identified as part of the routine organ donor screening process (NAT testing for HCV RNA). When a HCV RNA positive donor organ becomes available, the enrolled patient will be offered that kidney, If they accept, renal transplant will occur as per standard practice. Following transplant, patients will be tested for serum HCV RNA at day 7 and if patient becomes HCV viremic, they will be commenced on anti-HCV treatment (glecaprevir (300mg daily plus pibrentasvir 120mg daily, taken orally) for 12 weeks. Patients who test negative for HCV RNA at day 7 post-transplant will be re-tested at day 28 and then at week 8 and week 12 to confirm that they remain HCV RNA negative. If they become HCV RNA positive at day 28 / week 8 or week 12 they will progress to antiviral treatment. Adherence will be monitored closely as part of the protocol, and by the renal physicians looking after these patients (clinical review multiple times per week is standard for the first 3-6 months post renal transplant) - these will take the form of regular verbal reminder and reinforcement at each clinical review, as is standard for anti-rejection medication. HCV RNA will be monitored during treatment, as suppression of serum HCV RNA levels is an indicator of adherence and treatment response.
Sponsors
St Vincent's Hospital (Melbourne)
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria – recipient: Age 40-70 years On chronic haemodialysis or peritoneal dialysis Listed for an isolated kidney transplant No available living kidney donor Obtained agreement for participation from the patient's treating transplant nephrologist No evident contraindication to renal transplantation No active illicit substance abuse Weight at least 50kg Able to provide informed consent Inclusion criteria – donor organ: Detectable HCV RNA by NAT testing Age 18 to 65 years
Exclusion criteria
Exclusion criteria - recipient: - Hepatocellular carcinoma - Patients with a history of 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 - HIV positive - Hepatitis B surface antigen positive - HCV RNA positive (can be isolated HCV antibody positive) - Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes) - Persistently elevated liver transaminases (ALT > 5 x ULN) - Significant hepatic fibrosis on screening elastography (> F2 fibrosis – LSM > 9.5 kPa) Pregnant or nursing (lactating) women - Known allergy or intolerance to tacrolimus that would require post- transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and glecaprevir plus pibrentasvir - Waitlisted for a multi-organ transplant (e.g., pancreas-kidney, heart-kidney,etc.) - Cardiomyopathy (e.g., left-ventricular heart failure, pulmonary hypertension) that would preclude liver transplantation Exclusion criteria – donor organ: - Diabetes mellitus I or II - Anatomical issues in the kidney allograft that raise the risk of post-transplant complications (e.g. number or length of renal arteries or veins) - Confirmed HIV positive by NAT testing - Confirmed HBV positive (positive hepatitis B surface antigen and/or NAT testing) - Known previously failed treatment for HCV using a regimen with a direct-acting antiviral (can have received interferon monotherapy and/or interferon + ribavirin combination therapy)
Outcome results
None listed