Calcineurin Inhibitor Based Immunosuppression Withdrawal
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | Any - 19 |
| Updated: | 10/14/2017 |
| Start Date: | November 2007 |
| End Date: | November 2012 |
Novel Pilot Trial of Sirolimus, Mycophenolate Mofetil, and Corticosteroids Versus a Historic Control Population Receiving Calcineurin Inhibitors Based Immunosuppression
Damage and scarring of a transplanted kidney has become the most common cause of loss of the
transplanted kidney. This kidney damage is a complex process caused by many factors including
injury during obtaining and transplanting the kidney, injury from the immune system, injury
from infections, and injury from drugs used to stop rejection. This injury leads to scars
that decrease the kidney's ability to function properly, and over time the kidney is lost.
Prograf® (tacrolimus) has been one of the main drugs used to prevent rejection. However, when
used over time it has been shown to cause chronic damage and scarring in the transplanted
kidney.
The purpose of this experimental study is to determine whether children can safely be
withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus). Recent
research studies in adult transplantation have demonstrated that with the use of Rapamycin®
(sirolimus), it is possible to discontinue the use of Prograf (tacrolimus) with no increase
in rejection, with decreased scarring in the kidney, and with improvements in kidney function
and survival of the kidney. A total of 50 children will enroll in this study at university
centers around the country. This study will last about 3 years.
transplanted kidney. This kidney damage is a complex process caused by many factors including
injury during obtaining and transplanting the kidney, injury from the immune system, injury
from infections, and injury from drugs used to stop rejection. This injury leads to scars
that decrease the kidney's ability to function properly, and over time the kidney is lost.
Prograf® (tacrolimus) has been one of the main drugs used to prevent rejection. However, when
used over time it has been shown to cause chronic damage and scarring in the transplanted
kidney.
The purpose of this experimental study is to determine whether children can safely be
withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus). Recent
research studies in adult transplantation have demonstrated that with the use of Rapamycin®
(sirolimus), it is possible to discontinue the use of Prograf (tacrolimus) with no increase
in rejection, with decreased scarring in the kidney, and with improvements in kidney function
and survival of the kidney. A total of 50 children will enroll in this study at university
centers around the country. This study will last about 3 years.
Advances in immunosuppressive therapies in pediatrics have been associated with rapidly
falling incidence of acute rejection and improving allograft survival. In recent analyses of
the NAPRTCS database, acute rejection is no longer the most common cause of hospitalization
or allograft failure. Chronic rejection has now become the most common cause of allograft
failure and accounts for over 35% of allograft loss. Chronic rejection is a complex clinical
condition that includes both immunologic and non-immunologic causes and is more accurately
referred to as Chronic Allograft Nephropathy (CAN). Although Calcineurin inhibitors (CNI)
have played a central role in reducing acute rejection and improving allograft survival, it
has long been shown that they contribute to interstitial fibrosis and chronic allograft
nephropathy. Recent trials in adult transplantation have demonstrated that with the use of
the TOR-inhibitor, Sirolimus, it is possible to withdraw Calcineurin inhibitors with no
increase in rejection and with improvements in allograft function, interstitial fibrosis and
long term survival (1). We hypothesize that the use of Sirolimus (SRL) in pediatric kidney
transplantation will allow the withdrawal of Calcineurin inhibitor and improved kidney
function and long term survival. We plan to enroll 50 patients at the time of
transplantation. Patients will receive routine immunosuppression of CNI (Prograf),
Mycophenolate mofetil (Cellcept) and prednisone. Those patients with normal function and no
rejection episodes after 6 months of transplantation will undergo a slow conversion from
Prograf to Sirolimus (Rapamune). We will then assess the rate of rejection, allograft
function, fibrosis on biopsy, and allograft survival over the following 18 months.
falling incidence of acute rejection and improving allograft survival. In recent analyses of
the NAPRTCS database, acute rejection is no longer the most common cause of hospitalization
or allograft failure. Chronic rejection has now become the most common cause of allograft
failure and accounts for over 35% of allograft loss. Chronic rejection is a complex clinical
condition that includes both immunologic and non-immunologic causes and is more accurately
referred to as Chronic Allograft Nephropathy (CAN). Although Calcineurin inhibitors (CNI)
have played a central role in reducing acute rejection and improving allograft survival, it
has long been shown that they contribute to interstitial fibrosis and chronic allograft
nephropathy. Recent trials in adult transplantation have demonstrated that with the use of
the TOR-inhibitor, Sirolimus, it is possible to withdraw Calcineurin inhibitors with no
increase in rejection and with improvements in allograft function, interstitial fibrosis and
long term survival (1). We hypothesize that the use of Sirolimus (SRL) in pediatric kidney
transplantation will allow the withdrawal of Calcineurin inhibitor and improved kidney
function and long term survival. We plan to enroll 50 patients at the time of
transplantation. Patients will receive routine immunosuppression of CNI (Prograf),
Mycophenolate mofetil (Cellcept) and prednisone. Those patients with normal function and no
rejection episodes after 6 months of transplantation will undergo a slow conversion from
Prograf to Sirolimus (Rapamune). We will then assess the rate of rejection, allograft
function, fibrosis on biopsy, and allograft survival over the following 18 months.
Inclusion Criteria at Transplant:
- Age < 19 years (up to the day of the 19th birthday)
- Panel Reactive Antibody Level (PRA) <20% (Flow cytometry method)
- Recipient of first living donor or deceased donor renal transplantation
- Signed and dated informed consent (per local IRB standards)
Exclusion Criteria at Transplant:
- Recipients of multi-organ transplants (e.g. kidney/pancreas transplant, etc.)
- Peak PRA > 20% at any time
- Recipient of en-bloc kidneys
- Recipient of an organ from an HLA identical donor or a non-heart beating donor
- Pregnant or lactating
- Positive for HIV or an immunodeficiency virus
- History of malignancy
- Use of investigational agents within 4 weeks prior to transplantation
- Current use of terfenadine, cisapride, astemizole, or pimozide (unless discontinued
before administration of SRL)
- Known hypersensitivity to sirolimus
- Known hypersensitivity to Prograf, Cellcept, prednisone, Cremophor, HCO-60, or murine
products
We found this trial at
4
sites
Click here to add this to my saved trials
Emory University Emory University, recognized internationally for its outstanding liberal artscolleges, graduate and professional schools,...
Click here to add this to my saved trials
UCLA UCLA's primary purpose as a public research university is the creation, dissemination, preservation and...
Click here to add this to my saved trials
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
Click here to add this to my saved trials