Impact of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/2/2016 |
| Start Date: | September 2009 |
| End Date: | June 2011 |
| Contact: | Serban Constantinescu, MD, PhD |
| Email: | serban.constantinescu@tuhs.temple.edu |
| Phone: | 215-707-9171 |
Prospective Trial of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients With Chronic Allograft Nephropathy
The objective of this study is to examine the effect on allograft function and histology of
converting African American renal transplant recipients with chronic allograft nephropathy
(CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression
regimen.
The investigators hypothesize that the conversion from tacrolimus to sirolimus in African
American renal recipients will stabilize or improve renal allograft function, and stabilize
the histological progression of CAN. This conversion will have the potential to prolong
long-term graft survival in African American renal transplant patients.
GFR measurements, histological parameters on the allograft biopsy, as well as patient and
graft survival, incidence of acute rejection, and specific side effects will be monitored
and compared between the sirolimus conversion group and the patients who will be maintained
on tacrolimus.
converting African American renal transplant recipients with chronic allograft nephropathy
(CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression
regimen.
The investigators hypothesize that the conversion from tacrolimus to sirolimus in African
American renal recipients will stabilize or improve renal allograft function, and stabilize
the histological progression of CAN. This conversion will have the potential to prolong
long-term graft survival in African American renal transplant patients.
GFR measurements, histological parameters on the allograft biopsy, as well as patient and
graft survival, incidence of acute rejection, and specific side effects will be monitored
and compared between the sirolimus conversion group and the patients who will be maintained
on tacrolimus.
All African American renal transplant recipients (>3months and <5 years post-transplant) at
our institution that are currently on a tacrolimus based regimen will be screened. Subjects
with 10% or more decrease in glomerular filtration rate (GFR) from baseline, estimated by
the MDRD formula,65 and who meet all inclusion criteria will be consented to be enrolled in
the study. Baseline will be defined as the highest GFR estimated by MDRD formula, within 3
months of transplant.
Subjects who consent to participate in the study will undergo allograft biopsy and GFR
measurement by Gd-DTPA, and will be randomly assigned (2:1) to undergo conversion from
tacrolimus to sirolimus or to continue to receive tacrolimus.
The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg
po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will
be checked within a week and adjusted in a linear fashion to achieve a trough goal of
12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1
year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target
trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely.
Sirolimus trough levels will be monitored in the study as follows: weekly for the first
month, monthly from 1 - 6 months, every 3 months from 6 months - 1 year post conversion.
Subjects will continue to receive maintenance immunosuppression consisting of mycophenolate
mofetil 500mg to 1000 mg po bid as tolerated and corticosteroid taper per protocol
(maintenance of 2.5mg - 5mg po daily at 6 months post-transplant and then indefinitely). GFR
measurement by DTPA will be repeated at 6 months, and 1 year post conversion. The second
allograft biopsy will be performed at 1 year after sirolimus conversion.
The subjects assigned to the tacrolimus maintenance group (control group) represent our
present standard of care. The subjects will continue to receive prednisone, and
mycophenolate mofetil, similarly to the subjects assigned to the sirolimus conversion group.
In the tacrolimus maintenance group, the subjects will be monitored according to our current
clinic protocol, monthly between 3 months - 1 year post transplant, every two months in the
second year post-transplant and every 3 months after 2 years. The tacrolimus dose will be
adjusted to achieve a trough of 5-10ng/ml in subjects randomized to the control group which
is standard of care per protocol. GFR measurement by DTPA will be repeated at 6 months, and
1 year post randomization. The second allograft biopsy will be performed at 1 year post
randomization.
Patient and graft survival, and the incidence of acute rejection, proteinuria,
hyperlipidemia, anemia, leucopenia, thrombocytopenia, and other clinical parameters will be
monitored and compared between the sirolimus conversion group and the subjects who will be
maintained on tacrolimus.
our institution that are currently on a tacrolimus based regimen will be screened. Subjects
with 10% or more decrease in glomerular filtration rate (GFR) from baseline, estimated by
the MDRD formula,65 and who meet all inclusion criteria will be consented to be enrolled in
the study. Baseline will be defined as the highest GFR estimated by MDRD formula, within 3
months of transplant.
Subjects who consent to participate in the study will undergo allograft biopsy and GFR
measurement by Gd-DTPA, and will be randomly assigned (2:1) to undergo conversion from
tacrolimus to sirolimus or to continue to receive tacrolimus.
The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg
po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will
be checked within a week and adjusted in a linear fashion to achieve a trough goal of
12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1
year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target
trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely.
Sirolimus trough levels will be monitored in the study as follows: weekly for the first
month, monthly from 1 - 6 months, every 3 months from 6 months - 1 year post conversion.
Subjects will continue to receive maintenance immunosuppression consisting of mycophenolate
mofetil 500mg to 1000 mg po bid as tolerated and corticosteroid taper per protocol
(maintenance of 2.5mg - 5mg po daily at 6 months post-transplant and then indefinitely). GFR
measurement by DTPA will be repeated at 6 months, and 1 year post conversion. The second
allograft biopsy will be performed at 1 year after sirolimus conversion.
The subjects assigned to the tacrolimus maintenance group (control group) represent our
present standard of care. The subjects will continue to receive prednisone, and
mycophenolate mofetil, similarly to the subjects assigned to the sirolimus conversion group.
In the tacrolimus maintenance group, the subjects will be monitored according to our current
clinic protocol, monthly between 3 months - 1 year post transplant, every two months in the
second year post-transplant and every 3 months after 2 years. The tacrolimus dose will be
adjusted to achieve a trough of 5-10ng/ml in subjects randomized to the control group which
is standard of care per protocol. GFR measurement by DTPA will be repeated at 6 months, and
1 year post randomization. The second allograft biopsy will be performed at 1 year post
randomization.
Patient and graft survival, and the incidence of acute rejection, proteinuria,
hyperlipidemia, anemia, leucopenia, thrombocytopenia, and other clinical parameters will be
monitored and compared between the sirolimus conversion group and the subjects who will be
maintained on tacrolimus.
Inclusion Criteria:
- African American (self-identified) renal transplant recipients.
- Primary or re-transplant kidney-only recipients.
- Recipients on tacrolimus-based immunosuppression regimen.
- Time interval after transplant: at least 3 months but not greater than 5 years.
- Renal transplant recipients with 10% decrease in GFR from baseline.
- Women of childbearing potential must have a negative pregnancy test upon enrollment,
and must consent to receive contraceptive counseling and to use effective
contraception while enrolled in the study. Two reliable forms of contraception must
be used simultaneously unless abstinence is the chosen method.
Exclusion Criteria:
- GFR <40ml/min.
- Urine protein-to-creatinine ratio >0.5.
- Significant chronic allograft nephropathy grade 3 Banff score.
- Evidence of acute rejection episodes within the past 3 months.
- Evidence of active infection within the past month.
- Any malignancy except treated non-melanoma skin cancer within the past 3 years.
- Leucopenia <2,000/mm3 within the past month.
- Thrombocytopenia <100,000/mm3 within the past month.
- Total cholesterol >300mg/dl, despite adequate treatment.
- Triglycerides >500mg/dl, despite adequate treatment.
- Non-healed post-surgical or non-surgical wound.
We found this trial at
1
site
Temple University Temple University is many things to many people. A place to pursue life's...
Click here to add this to my saved trials
