Calcineurin Inhibitor Based Immunosuppression Withdrawal

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2012-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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The purpose of this experimental study is to determine whether children can safely be withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus).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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Pediatric Kidney Transplant Study of Sirolimus, Mycophenolate Mofetil, and Corticosteroids vs Calcineurin Inhibitor Based Immunosuppression

NCT00555373

Renal Transplant

COMPLETED NA

Pilot Study on the Use of Sirolimus to Treat Chronic Allograft Nephropathy in Children After Kidney Transplant

NCT00188955

Kidney Transplantation

COMPLETED PHASE4

Pediatric Kidney Transplant Without Calcineurin Inhibitors

NCT00023231

End-Stage Renal Disease

COMPLETED NA

Study Evaluating Two Different Sirolimus-based Immunosuppressive Regimens in Elderly Kidney Transplant Recipients

NCT00254709

Kidney Failure Graft Rejection Aged

COMPLETED PHASE4

Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation

NCT01517984

Kidney Transplant Recipients

TERMINATED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Renal Transplant

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sirolimus

Single arm

Group Type OTHER

Sirolimus

Intervention Type DRUG

1. Tacrolimus (Prograf®) At 6 months post-transplantation, patients will have Prograf® tapered by 25% per week such that they will be off of this medication by 7 months post-transplantation.
2. Sirolimus (Rapamune®):

At 6 months post-transplantation, all patients will be administered Sirolimus at a dose of 1.65-2.79 mg/m2/day as a tablet or liquid (administered q 12 hours).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sirolimus

1. Tacrolimus (Prograf®) At 6 months post-transplantation, patients will have Prograf® tapered by 25% per week such that they will be off of this medication by 7 months post-transplantation.
2. Sirolimus (Rapamune®):

At 6 months post-transplantation, all patients will be administered Sirolimus at a dose of 1.65-2.79 mg/m2/day as a tablet or liquid (administered q 12 hours).

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Rapamune Rapamycin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

* 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

Maximum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No