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

NCT05133050 | Not Yet Recruiting

• 1 other identifier: XHEC-C-2021-070-2
• Study Type: interventional
• Target: 510
• Locations: 1 country
• Sites: 1

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.

Conditions

Alport Syndrome

Outcome Measures

Primary Outcomes (1)

• Disease progression time

  a) Patients from no proteinuria to microalbuminuria; b) patients from microalbuminuria to dominant proteinuria.

  Up to 240 weeks

Secondary Outcomes (1)

• 5-year disease progression rate and eGFR slope

  Up to 240 weeks

Other Outcomes (1)

• Number of patients with adverse events

  Up to 240 weeks

Study Arms (2)

Experimental group

EXPERIMENTAL

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

Control group

NO INTERVENTION

No angiotensin converting enzyme inhibitor (ACEI) and other renin-angiotensin system inhibitors (including angiotensin II receptor antagonists, etc.) treatment.

Interventions

Ramipril DRUG

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.

Experimental group

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

MeSH Terms

Conditions

Nephritis, Hereditary

Interventions

Ramipril

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nephritis; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Gengru Jiang

CONTACT

+86-13917983703; jianggeng-ru@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 24, 2021
• Study Start: January 1, 2022
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 24, 2021

Record last verified: 2021-10

Locations

CN (1)