Safety and Efficacy of ACEI in Alport Syndrome Patients With COL4A3/COL4A4/COL4A5 Variants

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Efficacy of Early Angiotensin-converting Enzyme Inhibition in Patients With Alport Syndrome Carrying Pathogenic Heterozygous COL4A3,COL4A4 or COL4A5 Mutations

Conditions
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Alport Syndrome

Intervention / Treatment
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* Drug: Ramipril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 30-50 Years; Sex: All; 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>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. | Drug: Ramipril<br>* We use ACEI: ramipril, in this prospective, randomized, controlled and multicenter clinical trial to access the safety and efficacy in Alport syndrome patients carried COL4A3/COL4A4/COL4A5 variants.<br>|
| No Intervention: Control group<br>No angiotensin converting enzyme inhibitor (ACEI) and other renin-angiotensin system inhibitors (including angiotensin II receptor antagonists, etc.) treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression time | a) Patients from no proteinuria to microalbuminuria; b) patients from microalbuminuria to dominant proteinuria. | Up to 240 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year disease progression rate and eGFR slope | 5-year disease progression rate and eGFR slope | Up to 240 weeks |