Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Percentage of successful treatment of each arm
研究概览
简要总结
Patients with sickle cell anaemia may develop renal disease. In fact, renal disease occurred in 40% of adults patients (macroalbuminuria) with evolution to end-stage renal disease for half of them. Microalbuminuria is an early and sensitive marker of glomerular damage. It appears during the first decade and occurred in 20 to 25% of infants (2 to 18 years). Physiopathology of renal scarring is not well understood actually. Renal scarring might be due to glomerular hyperfiltration and vascular and endothelial damage. Angiotensin-converting enzyme inhibitors (ACE) were studied and used in diabetic nephropathy. In a study on 26 sickle cell adults, albuminuria was reduced about 50% by ACE compared to placebo after six months treatment. It might be interesting studying ACE efficacy in sickle cell children with microalbuminuria because renal disease is directly related to sickle cell and is not influenced by other cardiovascular risk factors like in adult patients.
We hypothesized to have a successful ACE treatment in more than 40% of cases after a nine months treatment period. A success is defined as a 50% reduction of the albuminuria/creatinuria ratio.
详细描述
This is a multicenter study. In order to include 72 patients we should pre-include 400 patients.
They will be included in the study after signing the protocol consent. For final inclusion in the study, two albuminuria/creatinuria ratio should be over or equal to 3mg/mmol. If so, inclusion will be done and patient will be randomized (placebo/enalapril) by CLEANWEB software. A blood sample will be done.
Treatment tolerance will be check up at day 7 (blood sample for renal tolerance and clinical examination), month 1(clinical examination), month 3(clinical examination), month 6(clinical examination), and month 9 (clinical examination). Treatment efficacy will be evaluated by albuminuria/creatinuria ratio at month 1, month 3, month 6, and month 9. Physiopathology of ACE efficacy will be studied at first day and month 9 by dosage of ICAM-1 and VCAM-1.
Treatment plain posology (0.5mg/kg/day) will be progressively obtained on a three months period, beginning at 0.2mg/kg/day.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sickle cell disease (SS, SC, Sb thalassemia, SD Punjab)
- •Affiliation to French Health benefits
- •Signed informed consent
- •Albuminemia / Creatinemia >= 3 mg / mmol (on 2 samples)
排除标准
- •Albuminemia / Creatinemia > 100 mg / mmol
- •Hypersensibility to enalapril
- •Angio-oedemas due to a previous treatment by ACE
- •idiopathic or hereditary angio-oedemas
- •cerebral echo-doppler
- •treatment by lithium digoxine
- •treatment by other ACE
- •congenital galactosemia
- •Pregnancy
研究组 & 干预措施
2
干预措施: Placebo (Drug)
1
Enalapril
干预措施: Enalapril (Drug)
结局指标
主要结局
Percentage of successful treatment of each arm
时间窗: at 9 months of treatment
Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).
次要结局
- Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1(at the first day and at 9 months of treatment.)
- Measure of albuminuria/ creatinuria ratio(at 1, 3 and 6 month of treatment.)