Pediatric Kidney Transplant Study of Sirolimus, Mycophenolate Mofetil, and Corticosteroids vs Calcineurin Inhibitor Based Immunosuppression (CNI-W)

This study has been completed.
Sponsor:
Collaborators:
Pfizer
The EMMES Corporation
Information provided by (Responsible Party):
Mark Benfield, MD, Pediatric Nephrology of Alabama
ClinicalTrials.gov Identifier:
NCT00555373
First received: November 6, 2007
Last updated: February 22, 2013
Last verified: February 2013
  Purpose

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The purpose of this experimental study is to determine whether children can safely be withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus).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


Condition Intervention
Renal Transplant
Drug: Sirolimus

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Novel Pilot Trial of Sirolimus, Mycophenolate Mofetil, and Corticosteroids Versus a Historic Control Population Receiving Calcineurin Inhibitors Based Immunosuppression

Resource links provided by NLM:


Further study details as provided by Pediatric Nephrology of Alabama:

Primary Outcome Measures:
  • This study has a primary endpoint of allograft function as determined by Schwartz GFR at 18 months after conversion to CNI free protocol (2 years post transplantation). [ Time Frame: 18 mos after conversion to CNI free protocol ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary outcomes will include biopsy proven acute rejection episodes, progression of quantitative interstitial fibrosis as determined by Sirius Red staining and digital image analysis, Allograft survival and patient survival [ Time Frame: measured at 12 and 24 months post transplant ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: November 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sirolimus
Single arm
Drug: 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).

Other Names:
  • Rapamune
  • Rapamycin

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00555373

Locations
United States, Alabama
Pediatric Nephrology of Alabama
Birmingham, Alabama, United States, 35205
United States, California
UCLA
Los Angeles, California, United States, 90095
Stanford University
Stanford, California, United States, 94305
United States, Georgia
Emory University
Atlanta, Georgia, United States
Sponsors and Collaborators
Pediatric Nephrology of Alabama
Pfizer
The EMMES Corporation
Investigators
Principal Investigator: Mark Benfield, M.D. Pediatric Nephrology of Alabama
  More Information

No publications provided

Responsible Party: Mark Benfield, MD, MD, Pediatric Nephrology of Alabama
ClinicalTrials.gov Identifier: NCT00555373     History of Changes
Other Study ID Numbers: WIRB Pr. No.: 20101428
Study First Received: November 6, 2007
Last Updated: February 22, 2013
Health Authority: United States:Western Institutional Review Board

Keywords provided by Pediatric Nephrology of Alabama:
Pediatric
Renal
Transplant

Additional relevant MeSH terms:
Mycophenolate mofetil
Sirolimus
Everolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014