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

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000936

Purpose

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	Intervention	Phase
Kidney Transplantation	Drug: OKT3 Drug: Oral Cyclosporine Drug: IV Cyclosporine	Phase III

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Cyclosporin Cyclosporine Muromonab CD3

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment
Official Title:	Controlled Trial of Induction Therapy in Renal Transplantation

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

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

Secondary Outcome Measures:

Two and four-year graft functions [ Time Frame: At 2 and 4 years ] [ Designated as safety issue: No ]
Safety with respect to viral infections and malignancies in children undergoing a renal transplant [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Frequency and severity of rejection episodes [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Time to first rejection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Length and frequency of hospitalization [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Nature of acute cellular rejection at a molecular level [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Nature of "heightened immune respons" of younger children by studying gene expression in surveillance biopsies [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Correlate intragraft events during rejection with cytokine profile in the peripheral blood [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	November 1999
Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Patients receiving induction therapy	Drug: OKT3 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.
B: Experimental 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.

Arms

Assigned Interventions

A: Experimental

Patients receiving induction therapy

Drug: OKT3

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.

B: Experimental

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.

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.

Eligibility

Ages Eligible for Study:	up to 20 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000936

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

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT IN01/OLN-359
Study First Received:	November 2, 1999
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00000936
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Cyclosporine
Clotrimazole
Miconazole

Tioconazole
Cyclosporins
Muromonab-CD3

Additional relevant MeSH terms:

Anti-Infective Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antifungal Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antirheumatic Agents
Dermatologic Agents
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009