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

Condition(s) targeted: Renal Insufficiency, Chronic

Intervention: Ramipril (Drug); placebo to ramipril (Drug); Ramipril (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Official(s) and/or principal investigator(s):
Oliver Gross, Prof., Study Chair, Affiliation: University Medical Center Goettingen, Department Nephrology and Rheumatology

Overall contact:
Oliver Gross, Prof., Phone: +49 (0)551 39, Ext: 6331, Email: gross.oliver@med.uni-goettingen.de

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 1: 1 ratio to receive once daily ramipril or placebo. 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 80, and the number of patients treated open label from Day 1 of the study aimed to be approximately 40.

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Time to next disease level

Incidence of Adverse Drug Events before progression

Secondary outcome:

Albuminuria after three years

Adverse Drug Events over three years

Minimum age: 24 Months. Maximum age: 18 Years. Gender(s): Both.

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 or I at screening (microhaematuria without microalbuminuria

or microalbuminuria [30-300 mg albumin/gCrea])

- 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 II, , 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

Oliver Gross, Prof., Phone: +49 (0)551 39, Ext: 6331, Email: gross.oliver@med.uni-goettingen.de

Dept. of Children and Adolescent Medicine, Cologne University Hospital, Cologne 50924, Germany; Recruiting
Markus Feldkötter, Dr.
Bernd Hoppe, Prof.
Markus Feldkötter, Dr., Principal Investigator
Michaela Geßner, Sub-Investigator
Bernd Hoppe, Prof., Sub-Investigator
Heike Hoyer-Kuhn, Dr., Sub-Investigator
Kai-Dietrich Nüsken, Dr., Sub-Investigator
Gesa Schalk, Sub-Investigator
Christina Taylan, Dr., Sub-Investigator

Dept. of Paediatrics, Essen University Hospital, Essen 45122, Germany; Recruiting
Peter F Hoyer, Prof.
Anja Büscher, Dr.
Peter F Hoyer, Prof., Principal Investigator
Rainer Büscher, Prof., Sub-Investigator
Anne-Margret Wingen, Prof., Sub-Investigator
Anja Büscher, Dr., Sub-Investigator

Clementine Children's Hospital, Frankfurt 60316, Germany; Recruiting
Kay Latta, PD
Matthias Hansen, MD
Kay Latta, Dr., Principal Investigator
Matthias Hansen, Dr., Sub-Investigator

Dept. of Pediatrics II, University Medical Center Goettingen, Goettingen 37075, Germany; Recruiting
Hildegard Zappel, Dr.
Oliver Gross, Prof.
Hildegard Zappel, Dr., Principal Investigator
Ekkehard Wilichowski, Prof., Sub-Investigator

Eppendorf University Hospital, Hamburg 20246, Germany; Recruiting
Markus Kemper, Prof.
Jun Oh, Dr.
Markus Kemper, Prof., Principal Investigator
Jun Oh, Dr., Sub-Investigator

Dept. of paediatric kidney, liver and metabolism diseases, MHH Hannover, Hannover 30625, Germany; Recruiting
Lars Pape, Prof.
Mirja Wedekin
Lars Pape, Prof., Principal Investigator
Mirja Wedekin, Dr., Sub-Investigator

Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg 69120, Germany; Recruiting
Burkhard Tönshoff, Prof.
Britta Höcker, Dr.
Burkhard Tönshoff, Prof., Principal Investigator
Britta Höcker, Dr., Sub-Investigator
Susanne Rieger, Dr., Sub-Investigator
Daniela Choukair, Dr., Sub-Investigator
Heiko Billing, Dr., Sub-Investigator
Alexander Fichtner, Dr., Sub-Investigator

KfH - Kidney Center for Children and Adolescents, University of Jena, Jena 07745, Germany; Recruiting
Ulrike John, Dr.
Michael Pohl, Dr.
Ulrike John, Dr., Principal Investigator
Michael Pohl, Dr., Sub-Investigator

Dept. for Children and Adolescent Medicine - KfH Kidney Center, St. Georg Hospital, Leipzig 04129, Germany; Recruiting
Michael Henn, Dr.
Simone Wygoda, Dr.
Michael Henn, Dr., Principal Investigator
Simone Wygoda, Dr., Sub-Investigator

Clinic for Children and Adolescent Medicine, Memmingen Hospital, Memmingen 87700, Germany; Recruiting
Henry Fehrenbach, Dr.
Tobias Hampel, Dr.
Henry Fehrenbach, Dr., Principal Investigator
Tobias Hampel, Dr., Sub-Investigator

Dr. von Haunersches Children's Hospital, Children's University Hospital Munich, Munich 80337, Germany; Recruiting
Lutz Weber, Dr.
Marcus Benz, Dr.
Lutz Weber, Dr., Principal Investigator
Marcus Benz, Dr., Sub-Investigator
Bärbel Lange-Sperandio, Dr., Sub-Investigator
Sabine Ponsel, Dr., Sub-Investigator

Dept. of Pediatric Nephrology / KfH Kidney Center, Children's University Hospital Münster, Münster 48149, Germany; Recruiting
Martin Konrad, Prof.
Birgitta Kranz, Dr.
Martin Konrad, Prof., Principal Investigator
Birgitta Kranz, Dr., Sub-Investigator
Jens König, Dr., Sub-Investigator

KfH Kidney Center for Children and Adolescent, Rostock University Hospital, Rostock 18057, Germany; Recruiting
Hagen Staude, Dr.
Ulrike Jacoby, Dr.
Hagen Staude, Dr., Principal Investigator
Ulrike Jacoby, Dr., Sub-Investigator
Heimke von Osten, Sub-Investigator

Related Information

Starting date: March 2012
Last updated: March 1, 2012