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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Sponsor:
Collaborators:
University Medical Center Goettingen
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
ClinicalTrials.gov Identifier:
NCT01485978
First received: December 2, 2011
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Renal Insufficiency, Chronic
Drug: Ramipril
Drug: placebo to ramipril
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 120
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)
Arms Assigned Interventions
Active Comparator: Ramipril blinded
oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years
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 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.
Drug: Ramipril
Oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol.

  Eligibility

Ages Eligible for Study:   24 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485978

Contacts
Contact: Oliver Gross, Prof. +49 (0)551 39 ext 6331 gross.oliver@med.uni-goettingen.de
Contact: Carsten Bramlage, Dr. +49 (0)551 39 ext 9825 c.bramlage@med.uni-goettingen.de

Locations
Germany
University Medical Center Goettingen Recruiting
Goettingen, Germany, 37075
Contact: Oliver Gross, Prof. Dr.         
Sponsors and Collaborators
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
University Medical Center Goettingen
German Federal Ministry of Education and Research
Investigators
Study Chair: Oliver Gross, Prof. University Medical Center Goettingen, Department Nephrology and Rheumatology
  More Information

Additional Information:
No publications provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Additional 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     History of Changes
Other Study ID Numbers: EARLY_PRO-TECT_ALPORT
Study First Received: December 2, 2011
Last Updated: August 7, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:
Alport Syndrome
chronic kidney disease
renal fibrosis
nephroprotection
pediatric study

Additional relevant MeSH terms:
Renal Insufficiency
Renal Insufficiency, Chronic
Nephritis, Hereditary
Kidney Diseases
Urologic Diseases
Urogenital Abnormalities
Nephritis
Congenital Abnormalities
Collagen Diseases
Connective Tissue Diseases
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 25, 2014