Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Time to next disease level
研究概览
简要总结
This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression.
Alport syndrome stages that describe the extent of renal damage and loss of function are defined as:
- 0 Microhaematuria without microalbuminuria (usually at birth)
- I Microalbuminuria (30-300 mg albumin/gCrea)
- II Proteinuria >300 mg albumin/gCrea
- III > 25% decline of normal renal function (creatinine clearance)
- IV End stage renal failure (ESRF)
Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60.
Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 24 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Definitive diagnosis of Alport syndrome: Kidney biopsy (patient or affected relative/s), and/or mutation analysis (hemizygous X-chromosomal or homozygous autosomal-recessive) and assessment of criteria for clinical diagnosis (haematuria, positive family history regarding kidney diseases, ocular changes, labyrinthine hearing loss)
- •Alport syndrome levels 0, I or II at screening (microhaematuria without microalbuminuria or microalbuminuria [30-300 mg albumin/gCrea]) or proteinuria >300 mg albumin/gCrea with GFR>80ml/min). Patients with Alport stage II are not subject to randomization but are treated opel label.
- •Aged between ≥24 months and <18 years at screening
- •Assent from patient and informed consent from parents/legal guardian
排除标准
- •Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier
- •Alport syndrome levels III, or IV (albuminuria >300 mg/g Crea, creatinine clearance <60 mL/min, or end stage renal failure [ESRF])
- •Known allergies or intolerances to ramipril or related compounds
- •Known contraindication for ACEi-therapy
- •Additional chronic renal, pulmonary or cardiac diseases
- •Pregnancy and lactation
研究组 & 干预措施
Ramipril blinded
oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years
干预措施: Ramipril (Drug)
placebo to ramipril
Oral placebo treatment to ramipril once daily for 3 years or until progress to next disease level. After progression to next disease level, patients will be unblinded, and ramipril treatment will be initiated.
干预措施: placebo to ramipril (Drug)
open label ramipril
Open label treatment with ramipril as per protocol, if randomization is refused.
干预措施: Ramipril (Drug)
结局指标
主要结局
Time to next disease level
时间窗: within 3 years
Time to progression of Alport Syndrome to the next disease level within 3 years under ramipril treatment compared to placebo, for all randomised patients.
Incidence of Adverse Drug Events before progression
时间窗: within 3 years
Incidence of adverse drug events (ADEs, e.g., angioedema, acute renal failure, hyperkalaemia) under ramipril treatment before disease progression compared to placebo before disease progression, for all randomised patients.
次要结局
- Albuminuria after three years(after 3 years)
- Adverse Drug Events over three years(after 3 years)