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

• ClinicalTrials.gov Identifier: NCT00000936
• Recruitment Status: Terminated
• First Posted: August 31, 2001
• Last Update Posted: January 11, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Kidney Transplantation	Drug: hOKT3; Drug: Oral Cyclosporine; Drug: IV Cyclosporine	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 292 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Controlled Trial of Induction Therapy in Renal Transplantation
• Study Start Date: November 1999
• Actual Study Completion Date: March 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: Induction; subjects receiving hOKT3 induction therapy	Drug: hOKT3; Administered both during and after transplantation in IV form. Dosage determined by individual weight and given for a maximum of 14 days.; Drug: Oral Cyclosporine; Administered orally as either sandimmune or neoral at a dose determined by weight. 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, for the duration of the study.
Active Comparator: Induction Free Therapy; Patients not receiving induction therapy	Drug: Oral Cyclosporine; Administered orally as either sandimmune or neoral at a dose determined by weight. 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, for the duration of the study.; Drug: IV Cyclosporine; Administered intravenously (IV) both during and after transplantation at a dosage determined by individual age.

Outcome Measures

Primary Outcome Measures :

1. To determine one-year graft function, as measured by graft survival and serum creatinine of children undergoing OKT3 induction versus no induction [ Time Frame: At 1 year ]
2. To compare the efficacy of Sandimmune and Neoral with respect to graft function [ Time Frame: Throughout study ]

Secondary Outcome Measures :

1. Two and four-year graft functions [ Time Frame: At 2 and 4 years ]
2. Safety with respect to viral infections and malignancies in children undergoing a renal transplant [ Time Frame: Throughout study ]
3. Frequency and severity of rejection episodes [ Time Frame: Throughout study ]
4. Time to first rejection [ Time Frame: Throughout study ]
5. Length and frequency of hospitalization [ Time Frame: Throughout study ]
6. Nature of acute cellular rejection at a molecular level [ Time Frame: Throughout study ]
7. Nature of "heightened immune response" of younger children by studying gene expression in surveillance biopsies [ Time Frame: Throughout study ]
8. Correlate intragraft events during rejection with cytokine profile in the peripheral blood [ Time Frame: Throughout study ]

Eligibility Criteria

• Ages Eligible for Study: up to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Maryland

Ilene Blechman-Krom

Rockville, Maryland, United States, 20850

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

The National Institute of Allergy and Infectious Diseases (NIAID) 

Division of Allergy, Immunology, and Transplantation (DAIT) 

Study Data/Documents: Individual Participant Data Set 

Identifier: SDY354
ImmPort study identifier is SDY354.

Study Protocol 

Identifier: SDY354
ImmPort study identifier is SDY354.

Study summary, -design, -demographics, -lab tests, -study files 

Identifier: SDY354
ImmPort study identifier is SDY354.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000936
• Other Study ID Numbers: DAIT IN01/OLN-359
• First Posted: August 31, 2001
• Last Update Posted: January 11, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Additional relevant MeSH terms:

Cyclosporine; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors