BK nephropathy Urological and Genital Diseases Unspecified nephritic syndrome
Conditions
Interventions
Amended as of 17/08/2010:
De novo transplant patients will have monthly measurements of urine or plasma BK virus at their centre. Once either urine or plasma is positive for BK, plasma will be sent to
Sponsors
University of Calgary (Canada)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 01/02/2013: 1. All adults (aged greater than or equal to 18 years, either sex) de novo renal transplant patients with grafts from both living donors and deceased donors and up to two renal transplants prior to the current transplant 2. Presence of BK viremia based on a positive BK virus deoxyribonucleis acid polymerase chain reaction (DNA PCR) in plasma, of any degree 3. Greater than 1 month post-kidney transplant 4. Provision of informed consent (self or legal representative) Previous inclusion criteria: 1. All adults (aged greater than or equal to 18 years, either sex) de novo renal transplant patients with grafts from both living donors and deceased donors and up to two renal transplants prior to the current transplant 2. Presence of BK viremia based on a positive BK virus deoxyribonucleis acid polymerase chain reaction (DNA PCR) in plasma, of any degree 3. Greater than 2 months post-kidney transplant 4. Provision of informed consent (self or legal representative)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 05/02/2013: 1. Fourth or subsequent renal transplant 2. Multiorgan transplant 3. Cold ischemia time for current transplant exceeding 36 hours 4. Pregnancy, breastfeeding , or women of child bearing potential not willing to use a reliable method of contraception 5. Current involvement in another interventional trial (observational follow-up is permitted) 6. Known allergy to sirolimus or leflunomide 7. Pre-existing liver disease including Hepatitis B or C 8. Poor renal function due to causes other than BK virus, as determined by the site Qualified Investigator Previous exclusion criteria: 1. Fourth or subsequent renal transplant 2. Multiorgan transplant 3. Cold ischemia time for current transplant exceeding 36 hours 4. Patients with BK viremia less than 2 months after transplant 5. Pregnancy or breastfeeding 6. Involvement in another drug trial 7. Known allergy to sirolimus or leflunomide 8. Pre-existing liver disease including hepatitis B or C Added 17/08/2010: 9. Persistent estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m^2 for a period of at least 2 weeks in duration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Amended as of 17/08/2010: Multiple failure times per subject will represent the primary study outcome. Failure events will be: 1. Doubling of serum creatinine or an increase of at least 100 umol/L 2. Need for renal replacement therapy for graft end-stage failure 3. Death Binary change in serum creatinine will be defined as 100% increase (relative change) or 100 umol/L increase (absolute change) as compared to the lowest value between randomisation and the first 2 months; the change must persist for at least one month, with the event date being the initial assessment date. This multiple event approach is implied by design as patients may experience further events once the first has occurred. The likelihood of these further events may change after the first has occurred and as a result of BK infection providing clinical and biological support to the existence of correlation in the competing risks data arising from the present study. The competing risks of these further events may change as a result of treatment. Initial information at time of registration: Multiple failure times per subject will represent the primary study outcome. Failure events will be: 1. Doubling of serum creatinine 2. Need for renal replacement therapy for graft end-stage failure, and 3. Death This multiple event approach is implied by design as patients may experience further events once the first has occurred. The likelihood of these further events may change after the first has occurred and as a result of BK infection providing clinical and biological support to the existence of correlation in the competing risks data arising from the present study. The competing risks of these further events may change as a result of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Amended as of 17/08/2010: 1. Rate of decline in renal function: based on decline in eGFR in mL/min/1.73 m2 using the MDRD prediction equation 2. Time to 50% increase in serum creatinine (relative change) or 50 umol/L increase (absolute change) as compared to the lowest value between randomization and the first 2 months (the change persisting for at least one month, with the event date being the initial assessment date) 3. Time to clearance of viremia, which will be defined as 2 sequential monthly measurements with undetectable BK viral DNA by PCR. 4. Biopsy proven acute rejection using the Banff 2007 criteria 5. Grade of BK nephropathy on biopsy at 12 months as defined by Nickeleit and Mihatsch in Transplant International (2006) 6. Chronic allograft nephropathy at 12 months based on the Banff 2007 and CADI scoring systems 7. Change in selected health related quality of life measures between treatment groups. HRQOL will be assessed using a spectrum of HRQOL instruments including a generic questionnaire (Short-Form 36 [SF-36]), and a preference-based questionnaire (Euroqol [EQ-5D]). The primary HRQOL measure will be the change in the Euroqol EQ-5D index score. 8. Differences in health care costs between the two strategies. Costs to be assessed will include the direct costs associated with each of the interventions (i.e. drug costs, laboratory monitoring costs), and the cost of other relevant transplant medications. In addition to collecting intervention-specific costs, we will also collect information for all patients on associated health care costs including the cost of hospitalization, the cost of outpatient day care visits (i.e. for non-protocol renal biopsies, medication infusions, etc), the cost of diagnostic imaging, and the cost of dialysis, for those patients requiring dialysis. Initial information at time of registration: 1. Rate of decline in renal function: based on decline in estimated glomerular filtration rate (eGFR) in mL/min/1.73^m2 using t | — |
Countries
Canada
Outcome results
None listed