A Study to Compare Treatment With Sirolimus Versus Standard Treatment in Patients Who Have Received a Kidney Transplant
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
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Children's Hospital Boston
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：1
Participants will receive SRL, CsA/tacrolimus, and corticosteroids for up to 36 months
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Oral tablet taken daily.
Dosage is dependent on weight and is titrated to target trough level.
他の名前：
Dosage in liquid or tablet form is dependent on body surface area and is titrated to target trough level.
他の名前：
dosage is in oral form titrated to target trough level
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実験的：2
Participants will receive standard CsA or tacrolimus-based double or triple drug therapy for up to 36 months
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Oral tablet taken daily.
Dosage is dependent on weight and is titrated to target trough level.
他の名前：
dosage is in oral form titrated to target trough level
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Safety and efficacy of sirolimus
時間枠：Throughout study
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Throughout study
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Composite endpoint of biopsy proven acute rejection, graft loss, or death
時間枠：At Months 6, 12, and 24
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At Months 6, 12, and 24
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Rate of clinically diagnosed acute rejection
時間枠：At months 6, 12, 24, and 36
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At months 6, 12, 24, and 36
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Rate of change in glomerular filtration rate
時間枠：At Month 18
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At Month 18
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Mean change in volume of allograft fibrosis
時間枠：At Months 6 and 18
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At Months 6 and 18
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Intragraft expression of cytokines
時間枠：Throughout study
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Throughout study
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Cytokine expression and subsequent development of chronic allograft nephropathy
時間枠：Throughout study
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Throughout study
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協力者と研究者
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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