Focal Segmental Glomerulosclerosis Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 1
- 主要终点
- The primary outcome is a 6-level ordinal variable defined based on the achievement of remission from proteinuria during the first 52 weeks after randomization.
研究概览
简要总结
The FSGS Clinical Trial is a multi-center, prospective, controlled, open label randomized trial designed to determine if treatment with mycophenolate mofetil (MMF) in conjunction with pulse steroids is superior to treatment with Cyclosporine-A (CSA) in inducing remission from proteinuria over 12 months.
详细描述
Background/Rationale. Primary FSGS is a leading cause of end stage renal disease in both children and adults, with complete loss of kidney function in 50% of patients over 10 years. Evidence-based treatment guidelines for FSGS have not been developed because of the lack of controlled studies and the small number of patients included in most reports. Over the past decade, a number of studies have reported therapeutic efficacy for treatment with Cyclosporine-A (CSA) in patients with nephrotic syndrome including patients with steroid resistant FSGS. There have been two controlled trials of treatment with CSA in steroid resistant FSGS, one in children and one in adult patients. Consequently, CSA is the only medication that has been documented to be efficacious in a controlled trial in both children and adults with steroid resistant FSGS. The experience with mycophenolate mofetil (MMF) in the treatment of patients with steroid resistant FSGS has been limited to uncontrolled trials in adult patients and children.
Patient Population. The patient population consists of children and adults between the ages of 2 and 40 years with steroid resistant FSGS.
Study Design. The experimental design is a multi-center, prospective, controlled, open label randomized trial comparing two treatment regimens, CSA vs. MMF/Pulse Steroids. The treatment regimens in both arms also include angiotensin converting enzyme inhibitor (ACEI) therapy and alternate day low dose prednisone. The CSA and MMF/Pulse steroid treatment regimens will be implemented over the first 26 weeks after randomization and continued to 52 weeks if a response in proteinuria occurs. The ACE inhibitor component continues for an additional 26 weeks after withdrawal of initial therapies.
Logistical Structure. Participants are recruited at over 130 participating sites in North America which are affiliated with one of five Core Coordinating Centers.
Primary Objectives. The primary objective of the trial is to determine if treatment with MMF/Pulse steroids is superior to treatment with CSA in inducing remission from proteinuria over 12 months. The main secondary objective is to determine if treatment with MMF/Pulse steroids is superior to treatment with CSA in inducing remissions which persist for at least 6 months following withdrawal of immunosuppressive therapy but while maintaining ACEI or angiotensin receptor blocker (ARB) therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 2-40 years at onset of signs or symptoms of FSGS
- •Age ≤ 40 years at time of randomization (randomization date before 41st birthday)
- •Estimated GFR ≥ 40 ml/min/1.73 m2 at most recent measure prior to randomization
- •For participants < age 18 years: Schwartz formula
- •For participants ≥ age 18 years: Cockroft-Gault formula
- •Up/c > 1.0 g protein/g creatinine on first am void at time of randomization
- •Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. A minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis.
- •Steroid resistance: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions:
- •minimal treatment duration of 4 weeks
- •minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent. In addition, the participant must not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 4-week course demonstrating steroid resistance.
- •Willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures.
- •Participants may be taking ACEI, ARB, Vitamin E, or lipid lowering therapy.
排除标准
- •Secondary FSGS
- •Prior therapy with sirolimus, CSA, tacrolimus, MMF, or azathioprin (Imuran)
- •Treated with cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 30 days
- •Lactation, pregnancy, or refusal of birth control in women of child bearing potential
- •Participation in another therapeutic trial concurrently or 30 days prior to randomization
- •Active/serious infection (including, but not limited to Hepatitis B, C, or HIV)
- •Malignancy
- •Blood pressure > 140/95 or > 95th percentile for age/height.
- •Participant is receiving 4 or more antihypertensive agents for the primary purpose of controlling blood pressure.
- •Participants with previously diagnosed diabetes mellitus type I or II: the diagnosis of DM I or II will be based on local criteria for participants with an established diagnosis. If hyperglycemia is detected during the screening period, the WHO criteria for the diagnosis of DM I and II will be used.
- •Clinical evidence of cirrhosis or chronic active liver disease
- •Abnormal laboratory values at the time of study entry:
- •Absolute neutrophil count (ANC) < 2000/mm3, or
- •Hematocrit (HCT) < 28%
- •History of significant gastrointestinal disorder, e.g, severe chronic diarrhea (> 5 watery stools per day) or active peptic ulcer disease.
- •Organ transplantation
- •Obesity (based on estimated dry weight at onset of disease prior to steroid therapy) defined as
- •BMI > 97th percentile for age if aged 2-20 years
- •BMI > 40 kg/m2 for age ≥21 years
- •Allergy to study medications
- •Inability to consent/assent
- •Note: Participants with conditions meeting exclusion criteria at a particular evaluation for eligibility may be re-evaluated at a later time to determine if the conditions have changed so that all entry criteria are met. In particular, if blood pressure > 140/95 or > 95th percentile for age/height while the participant is on less than three antihypertensive agents, the participant may be re-evaluated for eligibility after adding other antihypertensive agents so long as the total number of agents does not exceed three.
研究组 & 干预措施
1
Cyclosporin
干预措施: Cyclosporin (Drug)
2
MMF and Dexamethasone
干预措施: MMF and Dexamethasone (Drug)
结局指标
主要结局
The primary outcome is a 6-level ordinal variable defined based on the achievement of remission from proteinuria during the first 52 weeks after randomization.
时间窗: first 52 weeks after randomization.
次要结局
- The main secondary outcome is a 5-level ordinal variable defined based on the persistence of remissions after immunosuppressive agents are withdrawn.(based on the participant's level of proteinuria during the period from week 52 through week 78 following withdrawal of CSA or MMF/Pulse steroids)