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Trial record 1 of 1 for:    NCT02117596
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Calcineurin Inhibitor Based Immunosuppression Withdrawal (CNI-W)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02117596
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : April 21, 2014
The Emmes Company, LLC
Information provided by (Responsible Party):
Mark Benfield, MD, Pediatric Nephrology of Alabama

Tracking Information
First Submitted Date  ICMJE April 16, 2014
First Posted Date  ICMJE April 21, 2014
Last Update Posted Date April 21, 2014
Study Start Date  ICMJE November 2007
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Calcineurin Inhibitor Based Immunosuppression Withdrawal
Official Title  ICMJE Novel Pilot Trial of Sirolimus, Mycophenolate Mofetil, and Corticosteroids Versus a Historic Control Population Receiving Calcineurin Inhibitors Based Immunosuppression
Brief Summary

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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Renal Transplant
Intervention  ICMJE 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
Study Arms  ICMJE Sirolimus
Single arm
Intervention: Drug: Sirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2014)
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02117596
Other Study ID Numbers  ICMJE CNI Withdrawal
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mark Benfield, MD, Pediatric Nephrology of Alabama
Study Sponsor  ICMJE Pediatric Nephrology of Alabama
Collaborators  ICMJE
  • Pfizer
  • The Emmes Company, LLC
Investigators  ICMJE
Principal Investigator: Mark Benfield, M.D. Pediatric Nephrology of Alabama
PRS Account Pediatric Nephrology of Alabama
Verification Date April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP