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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Alport Syndrome
• Intervention / Treatment: Drug: Ramipril

• Study Type: Interventional
• Enrollment (Anticipated): 510
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gengru Jiang; Phone Number: +86-13917983703; Email: jianggeng-ru@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    • Contact: Gengru Jiang; Phone Number: +86-13917983703; Email: jianggeng-ru@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ramipril; 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.
No Intervention: Control group; No angiotensin converting enzyme inhibitor (ACEI) and other renin-angiotensin system inhibitors (including angiotensin II receptor antagonists, etc.) treatment.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events	Number of patients with adverse events	Up to 240 weeks

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Connective Tissue Diseases; Nephritis; Collagen Diseases; Syndrome; Nephritis, Hereditary; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Ramipril
• Other Study ID Numbers: XHEC-C-2021-070-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No