Efficacy and Safety Study to Delay Renal Failure in Children With Alport Syndrome

Renal Insufficiency, Chronic Clinical Trial

Official title:

Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01485978
• Other study ID #: EARLY_PRO-TECT_ALPORT
• Status: Completed
• Phase: Phase 3
• Start date: March 2012
• Est. completion date: March 2019

Study information

• Verified date: June 2020
• Source: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression.

Alport syndrome stages that describe the extent of renal damage and loss of function are defined as:

• 0 Microhaematuria without microalbuminuria (usually at birth)

• I Microalbuminuria (30-300 mg albumin/gCrea)

• II Proteinuria >300 mg albumin/gCrea

• III > 25% decline of normal renal function (creatinine clearance)

• IV End stage renal failure (ESRF)

Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60.

Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 2019
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Months to 18 Years

Eligibility

Inclusion Criteria:

• Definitive diagnosis of Alport syndrome: Kidney biopsy (patient or affected relative/s), and/or mutation analysis (hemizygous X-chromosomal or homozygous autosomal-recessive) and assessment of criteria for clinical diagnosis (haematuria, positive family history regarding kidney diseases, ocular changes, labyrinthine hearing loss)

• Alport syndrome levels 0, I or II at screening (microhaematuria without microalbuminuria or microalbuminuria [30-300 mg albumin/gCrea]) or proteinuria >300 mg albumin/gCrea with GFR>80ml/min). Patients with Alport stage II are not subject to randomization but are treated opel label.

• Aged between =24 months and <18 years at screening

• Assent from patient and informed consent from parents/legal guardian

Exclusion Criteria:

• Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier

• Alport syndrome levels III, or IV (albuminuria >300 mg/g Crea, creatinine clearance <60 mL/min, or end stage renal failure [ESRF])

• Known allergies or intolerances to ramipril or related compounds

• Known contraindication for ACEi-therapy

• Additional chronic renal, pulmonary or cardiac diseases

• Pregnancy and lactation

Related Conditions & MeSH terms

• Nephritis, Hereditary
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Ramipril
Ramipril (Delix) tablets containing 2.5 mg ramipril, oral application with 1 to 6 mg per body surface area ramipril once daily for 3 years.
• placebo to ramipril
Oral application of placebo to ramipril, once daily with 1 to 6 mg per body surface area for 3 years or until disease progression.
• Ramipril
Oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol.

Locations

Country	Name	City	State
Germany	University Medical Center Goettingen	Goettingen

Sponsors (3)

Lead Sponsor	Collaborator
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH	German Federal Ministry of Education and Research, University Medical Center Goettingen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Gross O, Tönshoff B, Weber LT, Pape L, Latta K, Fehrenbach H, Lange-Sperandio B, Zappel H, Hoyer P, Staude H, König S, John U, Gellermann J, Hoppe B, Galiano M, Hoecker B, Ehren R, Lerch C, Kashtan CE, Harden M, Boeckhaus J, Friede T; German Pediatric Nep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to next disease level	Time to progression of Alport Syndrome to the next disease level within 3 years under ramipril treatment compared to placebo, for all randomised patients.	within 3 years
Primary	Incidence of Adverse Drug Events before progression	Incidence of adverse drug events (ADEs, e.g., angioedema, acute renal failure, hyperkalaemia) under ramipril treatment before disease progression compared to placebo before disease progression, for all randomised patients.	within 3 years
Secondary	Albuminuria after three years	Albuminuria after 3 years corrected for baseline albuminuria for patients randomised to receive ramipril compared to placebo.	after 3 years
Secondary	Adverse Drug Events over three years	Incidence of ADEs (e.g., angioedema, acute renal failure, hyperkalaemia) during 3 years of treatment for patients randomised to receive ramipril compared to placebo.	after 3 years

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