Efficacy and Safety Study to Delay Renal Failure in Children With Alport Syndrome
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| ClinicalTrials.gov Identifier: NCT01485978 |
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Recruitment Status :
Completed
First Posted : December 6, 2011
Last Update Posted : June 17, 2020
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Insufficiency, Chronic | Drug: Ramipril Drug: placebo to ramipril | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 66 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome |
| Study Start Date : | March 2012 |
| Actual Primary Completion Date : | September 2018 |
| Actual Study Completion Date : | March 2019 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Ramipril blinded
oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years
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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. |
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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.
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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. |
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open label ramipril
Open label treatment with ramipril as per protocol, if randomization is refused.
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Drug: Ramipril
Oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol. |
- Time to next disease level [ Time Frame: within 3 years ]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 ]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 ]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 ]Incidence of ADEs (e.g., angioedema, acute renal failure, hyperkalaemia) during 3 years of treatment for patients randomised to receive ramipril compared to placebo.
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| Ages Eligible for Study: | 24 Months to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01485978
| Germany | |
| University Medical Center Goettingen | |
| Goettingen, Germany, 37075 | |
| Study Chair: | Oliver Gross, Prof. | University Medical Center Goettingen, Department Nephrology and Rheumatology |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH |
| ClinicalTrials.gov Identifier: | NCT01485978 |
| Other Study ID Numbers: |
EARLY_PRO-TECT_ALPORT |
| First Posted: | December 6, 2011 Key Record Dates |
| Last Update Posted: | June 17, 2020 |
| Last Verified: | June 2020 |
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Alport Syndrome chronic kidney disease renal fibrosis nephroprotection pediatric study |
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Ramipril Renal Insufficiency Renal Insufficiency, Chronic Nephritis, Hereditary Kidney Diseases Urologic Diseases Urogenital Abnormalities Nephritis |
Congenital Abnormalities Collagen Diseases Connective Tissue Diseases Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antihypertensive Agents |