The role of ACE inhibitors in early renal impairment in children with sickle cell disease: A randomized, double-blind study of enalapril versus placebo - MADREPIEC

INTERVENTION: Trade Name: ENALAPRIL Product Name: ENALAPRIL Pharmaceutical Form: Tablet INN or Proposed INN: ENALAPRIL CAS Number: 76095-16-4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5- Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Early renal impairment in children with sickle cell disease. MedDRA version: 8.1 Level: PT Classification code 10051051 Term: Sickle cell disease PRIMARY OUTCOME: Main Objective: Among children with sickle cell disease and albuminuria (confirmed by 3 measurements), to demonstrate that enalapril (at a dose of 0.5 mg/kg/day) improves the albuminuria-to-creatinine ratio (in mg/mmol) compared to a placebo. Primary endpoint(s): 1) Primary endpoint: - Treatment success rate for each arm at 9 months of treatment, i.e., 6 months of treatment at the maximum dose. Treatment success will be defined as a 50% reduction in the albumin-to-creatinine ratio (in mg/mmol). Albuminuria screening is performed by determining the albumin-to-creatinine ratio (in mg/mmol) in a urine sample. 24-hour urine collection is a reference method, but collecting 24-hour urine is difficult in children. The albumin-to-creatinine ratio is correlated with 24-hour albuminuria. This is a simple, reliable technique with fewer drawbacks for patients. 2) Secondary endpoint(s): - Measurement of the albumin-to-creatinine ratio at 1, 3, and 6 months of treatment; - Measurement of circulating forms of the cell adhesion molecules ICAM-1 and VCAM-1 at the start of treatment and at 9 months of treatment; Secondary Objective: 1- To monitor the evolution of albuminuria during treatment; 2- To evaluate the role of inflammation (ICAM-1, VCAM-1) in endothelial lesions initiating glomerular disease. To evaluate the evolution of cell adhesion molecule levels during treatment. INCLUSION CRITERIA: - Children with sickle cell disease (SS, SC, Sbeta-thalassemia, SDPunjab); - Age over 2 years and under 18 years. - Affiliation to a social security scheme or beneficiary status - Signature of consent by both parents or holders of parental authority and by the patient of legal age to give their opinion - Albuminuria to creatinine ratio greater than or equal to 3 mg/mmol on 3 samples. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no