Renal Transplant Infection
Conditions
Keywords
Envarsus
Brief summary
The purpose of this study is to assess if the use of Envarsus in place of Tacrolimus-immediate release (IR) in rapid metabolizers post kidney transplant will reduce incidence of BK infection. Efficacy evaluations will include measurement of urine and serum BK values at specified time points and review of any biopsy for BK virus nephropathy. Incidence of rejection, graft failure, and graft dysfunction will also be measured at specified time points.
Detailed description
This will be a single center prospective case control study. The investigators expect 40% of patients will develop BK viruria, 20% BK viremia, 5% BK viral nephropathy (BKVN). Patients will be managed using standard of care for the investigator's center (thymoglobulin induction, tacrolimus/mycophenolate/prednisone). Target tacrolimus level is 8-12 ng/mL for the first 6 months post transplant and 6-9 ng/mL thereafter. BK urine/serum is monitored at 1, 3, 6, 9, 2 months post transplant. A population of 100 patients is calculated to show significant difference for p value \< 0.05. Population: Study Group: Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at post-transplant month 1, who have a tacrolimus concentration/dose of \< 1 and a steady state therapeutic level will be eligible. Patients who consent will be converted to Envarsus at 20% reduction in tacrolimus dose. Control Group: Post transplant patients (kidney transplant alone performed between 10-2016 and time of enrollment) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at post-transplant month 1 and tacrolimus concentration/dose of \< 1 at post-transplant month 1, and BK data available for months 2, 3, 6, 9,12 post transplant.
Interventions
DRUGStudy Group
Patients will convert from current tacrolimus dose to an Envarsus dose that is 80% of the total tacrolimus dose. They will take envarsus once daily in the morning and have 24 hour trough levels monitored at the standard of care interval for tacrolimus. Dosing will be titrated to achieve goal levels.
DRUGControl Group
Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of \< 1 at month 1, and BK data available and month 2,3, 6,9,12.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years of age at the time of study entry * Recipient of a deceased or living donor kidney transplantation * Maintenance immunosuppression consisting of tacrolimus/ mycophenolate mofetil (MMF)/mycophenolic acid (MPA) (≥1000 mg/720 mg daily) ± prednisone (≤10 mg/day) * Patient is less than or at 8 weeks post transplant with a negative serum BK Virus screen at 3-4 weeks post transplant * Patient has a tacrolimus drug dose/concentration of \> 1 with therapeutic tacrolimus levels. * Women of childbearing potential defined as all women physiologically capable of becoming pregnant, must have reviewed Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) and have a negative pregnancy test upon study entry. * Female (and male) subjects with reproductive potential must agree to use a highly effective method of birth control for the duration of the study. Please note that according to the US product information for MMF/MPA, two reliable forms of contraception must be used simultaneously unless female sterilization, male sterilization, post-menopausal status or total abstinence is the chosen method.
Exclusion criteria
* Inability or unwillingness of a patient to give written informed consent or comply with study protocol * History of graft loss from acute rejection within 1 year after any previous kidney transplant * History of previous liver, heart, pancreas, or lung transplant * History of cellular rejection of current allograft prior to enrollment. * Serum BK virus ≥500 copies/ml by polymerase chain reaction (PCR) at the time of study entry * Female subjects who are pregnant or breast feeding * Participation in any other studies with investigational drugs or regimens in the preceding year from the time of study entry * Any condition or prior treatment which, in the opinion of the investigator, precludes study participation * Patients requiring the use of azathioprine or a class of drugs that inhibit the mammalian target of rapamycin (mTOR inhibitors) * Patients with active peptic ulcer disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Will Experience Less BK Infection Episodes Based on Viruria Results. | From baseline to 30 days | The evidence of BK virus infection will be measured by viruria \>500 copies. |
| Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | From baseline to 30 days | The evidence of BK virus infection will be measured by viremia \>500 copies. |
| Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results. | From baseline to 30 days | The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta). |
| Number of Participants With Viruria >500 Copies | at 300 days | Participants will experience less BK infection episodes based on viruria reported with \>500 copies. |
| Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | From baseline to 30 days | Safety will be assessed for all Grade 3 or higher infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria. | From baseline to 30 days | This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at month 1, whom have a concentration/dose of \< 1 and a steady state therapeutic level will be eligible. Patients will be converted to envarsus at 20% reduction in dose.
Study Group: Patients will convert from current tacrolimus dose to an Envarsus dose that is 80% of the total tacrolimus dose. They will take envarsus once daily in the morning and have 24 hour trough levels monitored at the standard of care interval for tacrolimus. Dosing will be titrated to achieve goal levels. | 43 |
| Control Group Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of \< 1 at month 1, and BK data available and month 2,3, 6,9,12.
Control Group: Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of \< 1 at month 1, and BK data available and month 2,3, 6,9,12. | 45 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Study Group | Control Group |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants | 40 Participants | 45 Participants |
| Age, Continuous | 50.19 years | 50.19 years | 50.19 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 78 Participants | 40 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 88 participants | 43 participants | 45 participants |
| Sex: Female, Male Female | 27 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Male | 61 Participants | 31 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 43 | 0 / 45 |
| other Total, other adverse events | 0 / 43 | 0 / 45 |
| serious Total, serious adverse events | 0 / 43 | 0 / 45 |
Outcome results
Primary
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.
Safety will be assessed for all Grade 3 or higher infection
Time frame: From baseline to 210 days
Population: data was not collected for this time period.
Primary
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.
Safety will be assessed for all Grade 3 or higher infection
Time frame: at 300 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | 1 Participants |
| Control Group | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | 0 Participants |
Primary
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.
Safety will be assessed for all Grade 3 or higher infection
Time frame: From baseline to 120 days
Population: data was not collected for this time period.
Primary
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.
Safety will be assessed for all Grade 3 or higher infection
Time frame: From baseline to 30 days
Population: data was not collected for this time period.
Primary
Number of Participants With Viruria >500 Copies
Participants will experience less BK infection episodes based on viruria reported with \>500 copies.
Time frame: at 300 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Number of Participants With Viruria >500 Copies | 14 Participants |
| Control Group | Number of Participants With Viruria >500 Copies | 22 Participants |
Primary
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.
The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).
Time frame: at 300 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results. | 1 Participants |
| Control Group | Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results. | 1 Participants |
Primary
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.
The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).
Time frame: From baseline to 120 days
Population: data was not collected for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.
The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).
Time frame: From baseline to 30 days
Population: data was not gathered at this time period
Primary
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.
The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).
Time frame: From baseline to 210 days
Population: data was not collected for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.
The evidence of BK virus infection will be measured by viremia \>500 copies.
Time frame: From baseline to 210 days
Population: data was not collected for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.
The evidence of BK virus infection will be measured by viremia \>500 copies.
Time frame: From baseline to 120 days
Population: data was not collected for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.
The evidence of BK virus infection will be measured by viremia \>500 copies.
Time frame: From baseline to 30 days
Population: data not gathered for this time period
Primary
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.
The evidence of BK virus infection will be measured by viremia \>500 copies.
Time frame: at 300 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | 8 Participants |
| Control Group | Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | 15 Participants |
Primary
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.
The evidence of BK virus infection will be measured by viruria \>500 copies.
Time frame: From baseline to 30 days
Population: data not gathered for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.
The evidence of BK virus infection will be measured by viruria \>500 copies.
Time frame: From baseline to 210 days
Population: data was not collected for this time period.
Primary
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.
The evidence of BK virus infection will be measured by viruria \>500 copies.
Time frame: From baseline to 120 days
Population: no data was collected for this time period.
Secondary
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.
This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria
Time frame: From baseline to 30 days
Population: data was not collected for this time period.
Secondary
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.
This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria
Time frame: From baseline to 120 days
Population: data was not collected for this time period.
Secondary
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.
This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria
Time frame: From baseline to 210 days
Population: data was not collected for this time period.
Secondary
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.
This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria
Time frame: at 300 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria. | 0 Participants |
| Control Group | Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria. | 0 Participants |