Efficacy and Safety Study to Delay Renal Failure in Children With Alport Syndrome
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.
Renal Insufficiency, Chronic
Drug: placebo to ramipril
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome|
- Time to next disease level [ Time Frame: within 3 years ] [ Designated as safety issue: No ]Time to progression of Alport Syndrome to the next disease level within 3 years under ramipril treatment compared to placebo, for all randomised patients.
- Incidence of Adverse Drug Events before progression [ Time Frame: within 3 years ] [ Designated as safety issue: Yes ]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.
- Albuminuria after three years [ Time Frame: after 3 years ] [ Designated as safety issue: No ]Albuminuria after 3 years corrected for baseline albuminuria for patients randomised to receive ramipril compared to placebo.
- Adverse Drug Events over three years [ Time Frame: after 3 years ] [ Designated as safety issue: Yes ]Incidence of ADEs (e.g., angioedema, acute renal failure, hyperkalaemia) during 3 years of treatment for patients randomised to receive ramipril compared to placebo.
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||August 2019|
|Estimated Primary Completion Date:||February 2019 (Final data collection date for primary outcome measure)|
Active Comparator: Ramipril blinded
oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years
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 Comparator: placebo to ramipril
Oral placebo treatment to ramipril once daily for 3 years or until progress to next disease level. After progression to next disease level, patients will be unblinded, and ramipril treatment will be initiated.
Drug: 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.
open label ramipril
Open label treatment with ramipril as per protocol, if randomization is refused.
Oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01485978
|Contact: Oliver Gross, Prof.||+49 (0)551 39 ext email@example.com|
|Contact: Carsten Bramlage, Dr.||+49 (0)551 39 ext firstname.lastname@example.org|
|University Medical Center Goettingen||Recruiting|
|Goettingen, Germany, 37075|
|Contact: Oliver Gross, Prof. Dr.|
|Study Chair:||Oliver Gross, Prof.||University Medical Center Goettingen, Department Nephrology and Rheumatology|