HCV, Hepatitis C, Kidney Transplant
Conditions
Brief summary
To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV) infected donors into recipients without HCV infection
Detailed description
This will be an open label, prospective, interventional, proof of concept study to evaluate the feasibility and safety of kidney transplant from HCV positive donors into HCV negative recipients using treatment with pan-genotypic direct acting antiviral therapies (DAAS) for treatment of post-transplant HCV transmission
Interventions
fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C
DRUGGlecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]
Three tablets once a day for 12 weeks for treatment of hepatitis C
Sponsors
Ohio State University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion/
Exclusion criteria
Inclusion Criteria: * Adult age \>18 years able to provide consent * Lack of available living donor * Calculated pre-transplant reactive panel (cPRA) of \<80% * Estimated post-transplant survival (EPTS) index \>20% and \<80% * Negative pre-transplant human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) serology and blood HCV polymerase chain reaction (PCR) * No clinically significant pre-transplant liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment | 12 weeks | Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment. |
| Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | 12 weeks | Elevation in liver enzyme \>5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant | 6 and 12 months | Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys. |
| Patient's Survival at 6 and 12 Months | 6 and 12 months | Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys. |
| Graft Survival at 6 and 12 Months | 12 months | Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys. |
Countries
United States
Participant flow
Recruitment details
54 Kidney transplant candidates were enrolled and listed on the Deceased Donor Kidney Wait-list to receive hepatitis C virus (HCV) viremic kidneys
Pre-assignment details
In total 18 patients were removed from the study: 9 participants received hepatitis C virus nucleic antigen test (HCV NAT) negative kidney transplants, 8 participants were removed from the kidney transplant deceased waiting-list, and 1 participant died prior to receiving kidney transplant
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.
Sofosbuvir / Velpatasvir Oral Tablet \[Epclusa\]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet \[MAVYRET\]: Three tablets once a day for 12 weeks for treatment of hepatitis C | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Removed from study due to reaching the study target of 30 transplant from hepatitis C viremic donors | 6 |
Baseline characteristics
| Characteristic | Intervention Group |
|---|---|
| Age, Continuous | 59 years |
| Donor (D) -Recipient (R) Cytomegalovirus (CMV) status CMV D-/R- | 7 Participants |
| Donor (D) -Recipient (R) Cytomegalovirus (CMV) status CMV D-/R+ | 10 Participants |
| Donor (D) -Recipient (R) Cytomegalovirus (CMV) status CMV D+/R+ | 3 Participants |
| Donor (D) -Recipient (R) Cytomegalovirus (CMV) status Cytomegalovirus (CMV) Donor (D)+/ Recipient (R-) | 10 Participants |
| Insurance type Private | 10 Participants |
| Insurance type Public, Medicaid | 2 Participants |
| Insurance type Public, Medicare | 18 Participants |
| Pre-Transplant Calculated Panel Reactive Antibody (cPRA) % | 0 percent |
| Primary cause of end stage kidney diseaes Adult polycystic kidney disease | 7 Participants |
| Primary cause of end stage kidney diseaes Diabetes Mellitus | 11 Participants |
| Primary cause of end stage kidney diseaes Hypertension | 4 Participants |
| Primary cause of end stage kidney diseaes Immunoglobin (IgA) nephropathy | 3 Participants |
| Primary cause of end stage kidney diseaes Others | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 21 Participants |
| Time on dialysis prior to transplant | 12 months |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 2 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies
Elevation in liver enzyme \>5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant.
Time frame: 12 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Group | Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | Liver enzyme elevation > 5 times upper limit | 2 Participants |
| Intervention Group | Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | Acute cholestatic hepatitis | 0 Participants |
| Intervention Group | Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | Medication intolerance to Direct Acting Antiviral | 0 Participants |
| Intervention Group | Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | No significant adverse effect reported | 28 Participants |
Primary
Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment
Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment | 28 Participants |
Secondary
Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant
Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys.
Time frame: 6 and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intervention Group | Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant | eGFR at 6 months | 54 ml/min/1.73m^2 |
| Intervention Group | Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant | eGFR at 12 months | 46 ml/min/1.73m^2 |
Secondary
Graft Survival at 6 and 12 Months
Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys.
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Group | Graft Survival at 6 and 12 Months | 6 months graft survival | 30 Participants |
| Intervention Group | Graft Survival at 6 and 12 Months | 12 months graft survival | 30 Participants |
Secondary
Patient's Survival at 6 and 12 Months
Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys.
Time frame: 6 and 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Group | Patient's Survival at 6 and 12 Months | 6 months patient survival | 30 Participants |
| Intervention Group | Patient's Survival at 6 and 12 Months | 12 months patient survival | 30 Participants |