Pediatric Kidney Transplant Without Calcineurin Inhibitors

National Institute of Allergy and Infectious Diseases (NIAID)

Status: Completed

Conditions: End-Stage Renal Disease

Treatments: Drug: Bactrim; Drug: Mycophenolate mofetil; Drug: Methylprednisolone/prednisone; Drug: Ganciclovir; Drug: Sirolimus; Drug: Lipitor; Drug: Daclizumab

Study type: Interventional

Funder types: NIH

Identifiers

NCT00023231

DAIT CN01

CN01

Details and patient eligibility

About

The purpose of this study is to see the effect of using drugs other than calcineurin inhibitors to improve the rate of kidney transplant failure.

Kidney transplantation can help children with end-stage kidney disease. However, it has been difficult to find treatment for donor graft rejection that does not have a lot of side effects. Researchers hope to find treatments (immunosuppressants) with fewer side effects. One approach is to avoid using calcineurin inhibitors and to try a new drug known as sirolimus instead. Another is to use steroids less often. This study will test whether using sirolimus, fewer steroid treatments, MMF, and certain antibodies will improve long-term graft survival in children receiving kidney transplants from living donors.

Full description

Renal transplantation is widely recognized as the treatment of choice for children with end-stage renal disease (ESRD). Although outcomes of renal transplantation in children have improved during the past decade, success has been limited by both non-specific tolerance and the complications associated with immunosuppressants. Steroids and calcineurin inhibitors have the most toxic side effects. Use of sirolimus for immunosuppression has not been associated with as many complications. Recent studies from Europe have demonstrated that sirolimus can be combined with MMF and steroids to provide excellent graft survival in the absence of calcineurin inhibitors. Steroid side-effects can be lessened by tapering the steroid dose to an every-other-day schedule. This protocol tests whether immunosuppression by IL-2r antibody, sirolimus, MMF, and alternate-day steroids will provide comparable graft survival for living donor recipients, compared to current immunosuppression, but with reduced complications of calcineurin inhibitors.

Evaluations prior to transplantation include a complete history and physical examination, CBC, liver function tests, and antibodies for CMV, EBV, HIV, HbsAG, and HCV. All appropriate vaccinations are provided before transplantation. Transplant recipients receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus. Serum sirolimus levels are measured so that doses can be adjusted to maintain certain blood levels of the drug. Bactrim and ganciclovir are given for infection prophylaxis. If the patient has consistent high levels of fasting cholesterol, treatment with lipitor may be given. A transplant biopsy is performed at the time of the transplant and at 3, 6, and 12 months post transplantation and at times when a rejection is suspected. A radionuclide GFR is done at the same time points, and at 1, 24, and 36 months. The protocol biopsies, blood, and urine samples will be analyzed by genomic methods to determine differences in gene expression post transplantation. In the event of a first acute rejection, patients are treated with Solu-Medrol for 3 consecutive days. A second rejection (at the discretion of the transplant center) or severe rejection (Banff Grade 3) is treated with antibody therapy and, after a second or severe rejection, the immunosuppressant regimen is changed. Patients are followed for 36 months with routine physical examinations and laboratory assessments.

Enrollment: 35 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 21 years of age and under.
• Are kidney recipients of living-donor grafts, except when living-donor grafts are identically matched.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are recipients of identical (HLA matched) living-donor grafts.
• Are recipients of cadaver-donor grafts.
• Have certain abnormal kidney diseases that may return.
• Have failed 2 or more previous kidney transplants.
• Have fat abnormalities that are inherited or present at high levels.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

1

Experimental group

Description:

Participants will receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus prior to transplantation. Bactrim and ganciclovir will be taken for infection prophylaxis. If the participant has consistent high levels of fasting cholesterol, treatment with lipitor may be given.

Treatment:

Drug: Daclizumab

Drug: Bactrim

Drug: Mycophenolate mofetil

Drug: Sirolimus

Drug: Methylprednisolone/prednisone

Drug: Lipitor

Drug: Ganciclovir