Information Alport Syndrome

ACE-inhibitor Ramipril versus Placebo in Early Stages of Alport Syndrome: Optimal Start of Therapy and Safety: Prospective, randomised, placebo-controlled, double-blinded, industry-independent, multi-center trial

Your trial centres: Bonn, Essen, Erlangen, Frankfurt, Göttingen, Hannover, Heidelberg, Jena, Cologne, Leipzig, Memmingen, Munich, Münster, Rostock and Paris. Numbers represent the families in the Alport patient organisation (in 2012).

Fig.1 Flow Chart

Trial Sites

The Goals of the Trial

with Alport syndrome for most nephrologists. However, constant therapy in children may lead to long-term drug toxicities. The aim of this trial is to test whether early therapy of children with Alport syndrome wiith Ramipril is safe and delays progression of renal failure and comorbidities. The Primary Efficacy Endpoint is „Time to progression to the next disease level within 3 years under treatment compared to placebo. The Primary Safety Endpoint is „Incidence of adverse drug events“ under treatment compared to placebo before disease progression.

Up to 40 eligible patients will be randomly assigned at a 1:1 ratio to receive ramipril or placebo. Patients who progress to the next disease level during the 3-year treatment period will be unblinded, and ramipril treatment will be initiated, if applicable.

Safety analyses will be performed for the full analysis set, i.e. the intent-to-treat (ITT) population. Efficacy analysis will be performed for the ITT population, and supporting analyses will be conducted on the per protocol population.  A continuous risk-benefit assessment, including the detailed analysis of Suspected Unexpected Serious Adverse Reactions (SUSARs) will be performed by the independent Data and Safety Monitoring Board (DSMB). In case of significant safety risks, study participation may be terminated for the individual patient or for the entire study.

Rationale of Trial and Statistical Calculation

Fig. 2    Rationale of Trial [Gross et al., Kidney Int 81: 494-501, 2012]

2a:    Endpoint dialysis: Start of therapy with a creatinine-clearance <60ml/min) (yellow) and even more at proteinuria >0.3g/day (green) delays renal failure by median of 3 (yellow) and 18 years (green). It remains unclear, if an even earlier start of therapy shows additional effects and is still safe (blue curve and question marks).

2b:    Patients with Alport syndrome have an impaired life-expectancy (median 55 years, red curve). ACE-inhibition (blue) significantly improves life-expectancy in patients with Alport syndrome. 

Sponsor: University Medicine Goettingen via Ministry of Education and Research

               supported by Sanofi-Aventis Germany GmbH

Monitoring by IFS Göttingen, Medical Statistics Prof. T. Friede, Göttingen

Coordinating Principal Investigator Prof. O. Gross, Göttingen

Leading Ethic Committee University Medicine Göttingen

Safety Board: Prof. M. Weber, Cologne; Prof. C. Licht, Toronto, Canada,                                       Prof. R. Hilgers, Göttingen;

supported by the German Alport patient organisation (www.alport-selbsthilfe.de)  

supported by the German Soc. of Ped. Nephrology (www.gpn-online.de)

Any Questions? Please contact our Trial Office Göttingen

Background Information about the Trial

Principal Investigator Prof. Dr. O. Gross (gross.oliver@med.uni-goettingen.de)

Study physician Dr. Jenny Krügel (jenny.kruegel@med.uni-goettingen.de)

Study physician Joseph Sonntag (joseph.sonntag@med.uni-goettingen.de)

Study nurse Frauke Weber (frauke.weber@med.uni-goettingen.de)

Phone +49-551-39-6910 or 6331

Fax       +49-551-39-6911

Email    studie@alport.de


last update 4/2014