Table of Contents
ISRN Pediatrics
Volume 2012, Article ID 436046, 6 pages
http://dx.doi.org/10.5402/2012/436046
Clinical Study

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients

1Department of Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch Straβe 40, 37075 Göttingen, Germany
2Department of Medical Statistics, University Medical Center Göttingen, 37075 Göttingen, Germany
3Institute for Applied Research and Clinical Trials GmbH (IFS) and Georg August University Göttingen, 37075 Göttingen, Germany

Received 4 March 2012; Accepted 11 April 2012

Academic Editors: R. Bhimma, T. V. Brogan, and S. Fanconi

Copyright © 2012 Oliver Gross et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are “time to progression to next disease level” and “incidence of adverse drug events before disease progression.” Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.