Safety and Efficacy of Early Angiotensin-converting Enzyme Inhibition in Patients With Alport Syndrome Carrying Pathogenic Heterozygous COL4A3,COL4A4 or COL4A5 Mutations
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 510
- 试验地点
- 1
- 主要终点
- Disease progression time
研究概览
简要总结
Alport syndrome (AS) is the second most common monogenic cause of end-stage renal failure (ESRF). AS is caused by variants in the COL4A3, COL4A4, and COL4A5 genes, which encode for the a3, a4, and a5 chains of type IV collagen. This trial is a prospective, randomized, controlled and multicenter trial. Mainly to assess the safety and efficacy of ramipril in Alport syndrome patients with variants of COL4A3/COL4A4/COL4A5.
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
- 30 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 30-50 Years;
- •Alport syndrome patients with variants of COL4A3/COL4A4/COL4A5; hematuria or microalbuminuria; eGFR>90 mL/min/1.73m2;
- •Patients with microscopic hematuria only;
- •Patients with microscopic hematuria and microalbuminuria: 30-300mg/24h or urine albumin/creatinine: 30-300mg/g;
- •No angiotensin converting enzyme inhibitor (ACEI) and other renin-angiotensin system inhibitors (including angiotensin II receptor antagonists, etc.) treatment.
排除标准
- •With primary or secondary kidney disease, including IgA nephropathy, membranous nephropathy, lupus nephropathy, benign renal arterioles, etc.;
- •Patients with a history of angioedema;
- •Hypovolemia or hypotension (systolic blood pressure less than 90mmHg and/or diastolic blood pressure less than 60mmHg);
- •Pregnant and lactating women;
- •Patients with bilateral renal artery stenosis or unilateral renal artery stenosis with solitary kidney;
- •Hyperkalemia, blood potassium>5.5mmol/L;
- •Severe aortic stenosis, severe mitral stenosis;
- •Treatment of drug allergy;
- •Hypertension or other diseases that may require treatment with angiotensin-converting enzyme inhibitors;
- •Disagree to participate in this research.
研究组 & 干预措施
Experimental group
Drug: Ramipril The initial dose of ramipril is 2.5 mg /d. The blood pressure, blood potassium and blood creatinine is measured every 1-2 weeks. If the blood pressure is normal, the dose of ramipril is adjusted to 5 mg /d after 2 weeks. If the blood pressure is low, the dose of ramipril is reduced to 1.25 mg /d until the blood pressure becomes normal, otherwise, stop ramipril using. If the blood potassium is high (>5.5mmol/L), the dose of ramipril is reduced to 1.25 mg /d until the blood potassium becomes normal, otherwise, stop ramipril using. If the blood creatinine is higher before therapy (≥30%), the dose of ramipril is reduced to 1.25 mg /d until the blood creatinine becomes normal, otherwise, stop ramipril using.
干预措施: Ramipril (Drug)
结局指标
主要结局
Disease progression time
时间窗: Up to 240 weeks
a) Patients from no proteinuria to microalbuminuria; b) patients from microalbuminuria to dominant proteinuria.
次要结局
- 5-year disease progression rate and eGFR slope(Up to 240 weeks)