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

Not Applicable

Not yet recruiting

• Conditions: Alport Syndrome
• Interventions: Drug: Ramipril

• Registration Number: NCT05133050
• Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-10
• Study First Submitted: 2021-10-27
• Study First Submitted QC: 2021-11-23
• Last Update Submitted: 2021-11-23
• Study First Posted: 2021-11-24
• Last Update Posted: 2021-11-24
• Study Start: 2022-01-01
• Primary Completion: 2024-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

1. Age: 30-50 Years;
2. Sex: All;
3. Alport syndrome patients with variants of COL4A3/COL4A4/COL4A5; hematuria or microalbuminuria; eGFR>90 mL/min/1.73m2;
4. Patients with microscopic hematuria only;
5. Patients with microscopic hematuria and microalbuminuria: 30-300mg/24h or urine albumin/creatinine: 30-300mg/g;
6. No angiotensin converting enzyme inhibitor (ACEI) and other renin-angiotensin system inhibitors (including angiotensin II receptor antagonists, etc.) treatment.

Exclusion Criteria

1. With primary or secondary kidney disease, including IgA nephropathy, membranous nephropathy, lupus nephropathy, benign renal arterioles, etc.;
2. Patients with a history of angioedema;
3. Hypovolemia or hypotension (systolic blood pressure less than 90mmHg and/or diastolic blood pressure less than 60mmHg);
4. Pregnant and lactating women;
5. Patients with bilateral renal artery stenosis or unilateral renal artery stenosis with solitary kidney;
6. Hyperkalemia, blood potassium>5.5mmol/L;
7. Severe aortic stenosis, severe mitral stenosis;
8. Treatment of drug allergy;
9. Hypertension or other diseases that may require treatment with angiotensin-converting enzyme inhibitors;
10. Disagree to participate in this research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Ramipril	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.

Primary Outcome Measures

Name	Time	Method
Disease progression time	Up to 240 weeks	a) Patients from no proteinuria to microalbuminuria; b) patients from microalbuminuria to dominant proteinuria.

Secondary Outcome Measures

Name	Time	Method
5-year disease progression rate and eGFR slope	Up to 240 weeks	5-year disease progression rate and eGFR slope

Trial Locations

Locations (1)

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China