A Study To Test An Anti-Rejection Therapy After Kidney Transplantation

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 3

Conditions: Kidney Transplantation

Treatments: Drug: IV Cyclosporine; Drug: hOKT3; Drug: Oral Cyclosporine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00000936

DAIT IN01/OLN-359

Details and patient eligibility

About

Kidney transplantation is often successful. However, despite aggressive anti-rejection drug therapy, some patients will reject their new kidney. This study is designed to test two anti-rejection approaches. Two medications in this study are currently used in children, but there is no information regarding which drug is safer or more effective.

Survival rates in renal transplantation are unacceptably low. Therefore, there is a need for an improved post-transplant treatment, such as the induction therapy used in this study.

Full description

Renal transplantation is recognized as the treatment of choice for children with chronic renal failure. However, patient and graft survival rates in young children are unacceptably low. In preliminary studies, OKT3 (a monoclonal antibody) induction therapy received post transplant has been more successful than standard immunosuppression alone in improving graft survival. This study is designed to assess the impact of induction therapy on graft survival in pediatric kidney transplant patients.

Patients are assigned to OKT3 induction or no induction in a 1:1 ratio. Randomization to oral cyclosporine of either Sandimmune or Neoral is also done in a 1:1 ratio. Group 1 receives OKT3 intraoperatively followed by Neoral. Group 2 receives OKT3 intraoperatively followed by Sandimmune. OKT3 is administered at 2.5 mg (if weight less than 30 kg) or 5 mg (if weight above 30 kg) per day for a maximum of 14 days. Group 3 receives IV cyclosporine followed by Neoral. Group 4 receives IV cyclosporine followed by Sandimmune. Oral cyclosporine is administered in a masked preparation. The dose for Sandimmune and Neoral is the same; patients 6 years of age and older begin at a dose of 15 mg/kg/day and patients under 6 years of age receive 500 mg/m2/day. Patients will receive concomitant medications including steroids (IV and po), Nifedipine, anti-CMV therapy, Bactrim, Azathioprine or Mycophenolate Mofetil. Kidney function, incidence of viral infection, graft survival, and incidence of malignancy will be measured to assess the role of OKT3 induction and the role of rejection in graft failure. Graft function will be evaluated at 1-, 2-, and 4-year intervals.

Enrollment: 292 patients

Sex: All

Ages: Under 20 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Children and young adults may be eligible for this study if they:

• Are not yet 21 years of age.
• Are receiving their first or second transplant.
• Are not pregnant.
• Agree to practice sexual abstinence or agree to use an effective
• method of birth control/contraception during the study and
• for 1 year after.

Exclusion Criteria

Children and young adults will not be eligible for this study if they:

• Are recipients of multiple organs other than kidneys.
• Are recipients of three or more transplants.
• Are HIV positive.
• Are Hepatitis B surface antigen positive.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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292 participants in 2 patient groups

Induction

Experimental group

Description:

subjects receiving hOKT3 induction therapy

Treatment:

Drug: Oral Cyclosporine

Drug: hOKT3

Induction Free Therapy

Active Comparator group

Description:

Patients not receiving induction therapy

Treatment:

Drug: Oral Cyclosporine

Drug: IV Cyclosporine