Efficacy and Safety Study to Delay Renal Failure in Children With Alport Syndrome - Full Text View

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 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.

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:

Genetics Home Reference related topics: Alport syndrome

MedlinePlus related topics: Chronic Kidney Disease

Drug Information available for: Ramipril

U.S. FDA Resources

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 2017
Estimated Primary Completion Date:	February 2017 (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 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

Contacts and Locations

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
Dept. of Children and Adolescent Medicine, Cologne University Hospital	Recruiting
Cologne, Germany, 50924
Contact: Markus Feldkötter, Dr.
Contact: Bernd Hoppe, Prof.
Principal Investigator: Markus Feldkötter, Dr.
Sub-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.
Dept. of Paediatrics, Essen University Hospital	Recruiting
Essen, Germany, 45122
Contact: Peter F Hoyer, Prof.
Contact: Anja Büscher, Dr.
Principal Investigator: Peter F Hoyer, Prof.
Sub-Investigator: Rainer Büscher, Prof.
Sub-Investigator: Anne-Margret Wingen, Prof.
Sub-Investigator: Anja Büscher, Dr.
Clementine Children's Hospital	Recruiting
Frankfurt, Germany, 60316
Contact: Kay Latta, PD
Contact: Matthias Hansen, MD
Principal Investigator: Kay Latta, Dr.
Sub-Investigator: Matthias Hansen, Dr.
Dept. of Pediatrics II, University Medical Center Goettingen	Recruiting
Goettingen, Germany, 37075
Contact: Hildegard Zappel, Dr.
Contact: Oliver Gross, Prof.
Principal Investigator: Hildegard Zappel, Dr.
Sub-Investigator: Ekkehard Wilichowski, Prof.
Eppendorf University Hospital	Recruiting
Hamburg, Germany, 20246
Contact: Markus Kemper, Prof.
Contact: Jun Oh, Dr.
Principal Investigator: Markus Kemper, Prof.
Sub-Investigator: Jun Oh, Dr.
Dept. of paediatric kidney, liver and metabolism diseases, MHH Hannover	Recruiting
Hannover, Germany, 30625
Contact: Lars Pape, Prof.
Contact: Mirja Wedekin
Principal Investigator: Lars Pape, Prof.
Sub-Investigator: Mirja Wedekin, Dr.
Center for Child and Adolescent Medicine, Heidelberg University Hospital	Recruiting
Heidelberg, Germany, 69120
Contact: Burkhard Tönshoff, Prof.
Contact: Britta Höcker, Dr.
Principal Investigator: Burkhard Tönshoff, Prof.
Sub-Investigator: Britta Höcker, Dr.
Sub-Investigator: Susanne Rieger, Dr.
Sub-Investigator: Daniela Choukair, Dr.
Sub-Investigator: Heiko Billing, Dr.
Sub-Investigator: Alexander Fichtner, Dr.
KfH - Kidney Center for Children and Adolescents, University of Jena	Recruiting
Jena, Germany, 07745
Contact: Ulrike John, Dr.
Contact: Michael Pohl, Dr.
Principal Investigator: Ulrike John, Dr.
Sub-Investigator: Michael Pohl, Dr.
Dept. for Children and Adolescent Medicine - KfH Kidney Center, St. Georg Hospital	Recruiting
Leipzig, Germany, 04129
Contact: Michael Henn, Dr.
Contact: Simone Wygoda, Dr.
Principal Investigator: Michael Henn, Dr.
Sub-Investigator: Simone Wygoda, Dr.
Clinic for Children and Adolescent Medicine, Memmingen Hospital	Recruiting
Memmingen, Germany, 87700
Contact: Henry Fehrenbach, Dr.
Contact: Tobias Hampel, Dr.
Principal Investigator: Henry Fehrenbach, Dr.
Sub-Investigator: Tobias Hampel, Dr.
Dr. von Haunersches Children's Hospital, Children's University Hospital Munich	Recruiting
Munich, Germany, 80337
Contact: Lutz Weber, Dr.
Contact: Marcus Benz, Dr.
Principal Investigator: Lutz Weber, Dr.
Sub-Investigator: Marcus Benz, Dr.
Sub-Investigator: Bärbel Lange-Sperandio, Dr.
Sub-Investigator: Sabine Ponsel, Dr.
Dept. of Pediatric Nephrology / KfH Kidney Center, Children's University Hospital Münster	Recruiting
Münster, Germany, 48149
Contact: Martin Konrad, Prof.
Contact: Birgitta Kranz, Dr.
Principal Investigator: Martin Konrad, Prof.
Sub-Investigator: Birgitta Kranz, Dr.
Sub-Investigator: Jens König, Dr.
KfH Kidney Center for Children and Adolescent, Rostock University Hospital	Recruiting
Rostock, Germany, 18057
Contact: Hagen Staude, Dr.
Contact: Ulrike Jacoby, Dr.
Principal Investigator: Hagen Staude, Dr.
Sub-Investigator: Ulrike Jacoby, Dr.
Sub-Investigator: Heimke von Osten

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:

Related Information This link exits the ClinicalTrials.gov site

No publications provided

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:	March 1, 2012
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:

Nephritis, Hereditary
Renal Insufficiency
Renal Insufficiency, Chronic
Urogenital Abnormalities
Nephritis
Kidney Diseases
Urologic Diseases
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 May 16, 2013