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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Group | Experimental | 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. |
|
| Control Group | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Study Group | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Participants Will Experience Less BK Infection Episodes Based on Viruria Results. | The evidence of BK virus infection will be measured by viruria >500 copies. | From baseline to 30 days |
| Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | The evidence of BK virus infection will be measured by viremia >500 copies. | From baseline to 30 days |
| 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). | From baseline to 30 days |
| Participants Will Experience Less BK Infection Episodes Based on Viruria Results. | The evidence of BK virus infection will be measured by viruria >500 copies. | From baseline to 120 days |
| Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | The evidence of BK virus infection will be measured by viremia >500 copies. | From baseline to 120 days |
| 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). | From baseline to 120 days |
| Participants Will Experience Less BK Infection Episodes Based on Viruria Results. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | From baseline to 30 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Graham C Towns, MD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | the patient who died was not included in the statistics |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | data not gathered for this time period. | Posted | From baseline to 30 days |
|
at 300 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Graham Towns, MD | University of Alabama at Birmingham | (205)934-1801 | gtowns@uabmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 5, 2022 | Dec 19, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D035061 | Control Groups |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
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|
|
| Control Group | Drug | 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. |
|
|
The evidence of BK virus infection will be measured by viruria >500 copies. |
| From baseline to 210 days |
| Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | The evidence of BK virus infection will be measured by viremia >500 copies. | From baseline to 210 days |
| 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). | From baseline to 210 days |
| Number of Participants With Viruria >500 Copies | Participants will experience less BK infection episodes based on viruria reported with >500 copies. | at 300 days |
| Participants Will Experience Less BK Infection Episodes Based on Viremia Results. | The evidence of BK virus infection will be measured by viremia >500 copies. | at 300 days |
| 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). | at 300 days |
| Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | From baseline to 30 days |
| Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | From baseline to 120 days |
| Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | From baseline to 210 days |
| Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | at 300 days |
| 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 |
| From baseline to 120 days |
| 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 | From baseline to 210 days |
| 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 | at 300 days |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. |
|
| 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. | data not gathered for this time period | Posted | From baseline to 30 days |
|
|
| 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). | data was not gathered at this time period | Posted | From baseline to 30 days |
|
|
| 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. | no data was collected for this time period. | Posted | From baseline to 120 days |
|
|
| 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. | data was not collected for this time period. | Posted | From baseline to 120 days |
|
|
| 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). | data was not collected for this time period. | Posted | From baseline to 120 days |
|
|
| 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. | data was not collected for this time period. | Posted | From baseline to 210 days |
|
|
| 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. | data was not collected for this time period. | Posted | From baseline to 210 days |
|
|
| 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). | data was not collected for this time period. | Posted | From baseline to 210 days |
|
|
| Primary | Number of Participants With Viruria >500 Copies | Participants will experience less BK infection episodes based on viruria reported with >500 copies. | Posted | Count of Participants | Participants | at 300 days |
|
|
|
| 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. | Posted | Count of Participants | Participants | at 300 days |
|
|
|
| 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). | Posted | Count of Participants | Participants | at 300 days |
|
|
|
| Primary | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | data was not collected for this time period. | Posted | From baseline to 30 days |
|
|
| Primary | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | data was not collected for this time period. | Posted | From baseline to 120 days |
|
|
| Primary | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | data was not collected for this time period. | Posted | From baseline to 210 days |
|
|
| Primary | Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0. | Safety will be assessed for all Grade 3 or higher infection | Posted | Count of Participants | Participants | at 300 days |
|
|
|
| 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 | data was not collected for this time period. | Posted | From baseline to 30 days |
|
|
| 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 | data was not collected for this time period. | Posted | From baseline to 120 days |
|
|
| 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 | data was not collected for this time period. | Posted | From baseline to 210 days |
|
|
| 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 | Posted | Count of Participants | Participants | at 300 days |
|
|
|
| 1 |
| 43 |
| 0 |
| 43 |
| 0 |
| 43 |
| EG001 | 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. | 0 | 45 | 0 | 45 | 0 | 45 |
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| D008722 | Methods |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |