A Study to Compare Treatment With Sirolimus Versus Standard Treatment in Patients Who Have Received a Kidney Transplant

Kidney Transplantation Clinical Trial

Official title:

An Open-Label, Comparative Study of the Effect of Sirolimus Versus Standard Treatment on Clinical Outcomes and Histologic Progression of Allograft Nephropathy in High Risk Pediatric Renal Transplant Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005113
• Other study ID #: DAIT SRL1
• Secondary ID: DAIT 0468E1-217-
• Status: Terminated
• Phase: Phase 3
• First received: April 14, 2000
• Last updated: March 12, 2012
• Start date: July 1999
• Est. completion date: March 2006

Study information

• Verified date: March 2012
• Source: Children's Hospital Boston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney transplants. SRL is a new medication that may prevent the body's immune system from rejecting organ transplants.

After receiving a kidney transplant, the body recognizes the donated kidney as a foreign invader and triggers the immune system to attack the kidney. This can lead to rejection of the new kidney and a failed transplant. To help reduce the risk of kidney rejection, transplant patients are given immunosuppressant drugs, which reduce the body's normal immune response and allow the transplanted organ to function. CsA or tacrolimus are two drugs that are often given to transplant patients. However, these are powerful drugs, and it can cause serious side effects and put a patient at increased risk for infections. SRL is a new drug that has been shown to reduce a transplant patient's chance of rejecting a new kidney, without serious side effects. This study is necessary to test the safety and effectiveness of SRL in children.

Description:

Successful kidney transplantation has gradually improved over the years; much of the improvement has resulted from the use of CsA. However, adequate and tolerable immunosuppression is difficult to achieve with CsA, and rejection episodes are still frequent. CsA is nephrotoxic, with drug toxicity often masking rejection episodes. Other immunosuppressant therapies can result in a range of complications, including metabolic disturbances, adrenocortical insufficiency, and increased risk for infections. Therefore, more effective drugs with less toxicity are needed to prevent acute rejection, especially in the pediatric population where the overall graft survival rate remains significantly lower when compared with that of adult transplant recipients. SRL is an immunosuppressive agent being developed for the prophylaxis of acute renal allograft rejection. SRL has a unique mechanism of action. It inhibits T and B cell activity. In Phase I and II trials in adults, SRL was generally well tolerated and exhibited no apparent nephrotoxic properties, and significantly lower rates of rejection were seen with SRL when compared to placebo.

Patients receive extensive prestudy screening, which includes a renal core biopsy, chest x-ray, bone density study, blood tests, and glomerular filtration rate (GFR). Patients are then randomly assigned to 1 of 2 study treatment groups in a 2:1 ratio (142 patients receive SRL, CsA/tacrolimus, and corticosteroids and 71 patients receive standard CsA or tacrolimus-based double or triple drug therapy). SRL is administered as an oral dose of 3 mg/m2/day. Patients are followed for 3 years on therapy, and then for 1 month of follow-up. A renal core biopsy is performed at the time of study entry and at Months 6, 18, and at early termination of patient in study. Patients undergo physical examinations and various blood tests at specified time intervals during the 37-month study period. Efficacy is assessed by comparing the composite endpoint of biopsy-proven acute rejection, graft loss, or death after 36 months of treatment. Safety is assessed by comparing the composite endpoint of graft loss or death after 36 months of treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 102
• Est. completion date: March 2006
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

Inclusion Criteria

Your child may be eligible for this study if he/she:

• Has received a kidney transplant.

• Has experienced 1 or more episodes of acute rejection or chronic rejection; a rejection episode must have responded to treatment and have occurred at least 30 days before study enrollment.

• Has stable kidney function at the time of study enrollment.

• Is 20 years of age or younger.

• Has written informed consent of parent or guardian if under the age of 18.

• Agrees to use birth control during the study and for 3 months following treatment.

Exclusion Criteria

Your child will not be eligible for this study if he/she:

• Has a history of cancer.

• Has received a multi-organ transplant (more than a kidney).

• Has an active infection.

• Has an abnormal chest X-ray.

• Cannot provide a kidney biopsy at time of study entry.

• Is allergic to sirolimus.

• Has received experimental drugs within 4 weeks of study entry.

• Is pregnant.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Failure, Chronic
• Kidney Transplantation

Intervention

Drug:
• Cyclosporine
Oral tablet taken daily. Dosage is dependent on weight and is titrated to target trough level.
• Sirolimus
Dosage in liquid or tablet form is dependent on body surface area and is titrated to target trough level.
• Tacrolimus
dosage is in oral form titrated to target trough level

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Boston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and efficacy of sirolimus		Throughout study	Yes
Secondary	Composite endpoint of biopsy proven acute rejection, graft loss, or death		At Months 6, 12, and 24	Yes
Secondary	Rate of clinically diagnosed acute rejection		At months 6, 12, 24, and 36	No
Secondary	Rate of change in glomerular filtration rate		At Month 18	No
Secondary	Mean change in volume of allograft fibrosis		At Months 6 and 18	No
Secondary	Intragraft expression of cytokines		Throughout study	No
Secondary	Cytokine expression and subsequent development of chronic allograft nephropathy		Throughout study	No