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.