Calcineurin Inhibitor Based Immunosuppression Withdrawal

NCT02117596 | Completed DMC

• 1 other identifier: CNI Withdrawal
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

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 The purpose of this experimental study is to determine whether children can safely be withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus).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

Conditions

Renal Transplant

Keywords

Pediatric; Renal; Transplant

Outcome Measures

Primary Outcomes (1)

• 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).

  18 mos after conversion to CNI free protocol

Secondary Outcomes (1)

• 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

  measured at 12 and 24 months post transplant

Study Arms (1)

Sirolimus

OTHER

Single arm

Drug: Sirolimus

Interventions

Sirolimus 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).

Also known as: Rapamune, Rapamycin

Sirolimus

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pediatric Nephrology of Alabama: lead
• Pfizer: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (4)

Pediatric Nephrology of Alabama

Birmingham, Alabama, 35205, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Emory University

Atlanta, Georgia, United States

Location

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Mark Benfield, M.D.

  Pediatric Nephrology of Alabama

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 21, 2014
• Study Start: November 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 21, 2014

Record last verified: 2014-04

Locations

US (4)