ESCAPE Trial

Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CKD in Pediatric Patients (NCT00221845)

N Engl J Med 2008; 361:1639-50​​​​​​​

The ESCAPE Trial was a landmark RCT initiated and executed by our Consortium. We investigated whether intensified blood-pressure control aimed at achieving 24-hour blood-pressure levels in the low range of normal would slow the progression of renal disease in children with CKD. Between April 1999 and December 2001, 465 children aged 3-17 years with eGFR of 15 to 18 ml/min/1.73 m2 were screened and 385 included in the trial at 33 European pediatric nephrology units.

Patients were randomly assigned to intensified blood-pressure control (with a target 24-hour mean arterial pressure below the 50th percentile) or conventional blood-pressure control (mean arterial pressure in the 50th to 95th percentile). To that end, all patients received the ACE inhibitor ramipril at a fixed dose (6 mg/m2/day). The patients randomized for intensified blood pressure control, if required, were prescribed additional antihypertensive drugs not targeting the renain angiotensin system. Study visits were performed every two months, and ambulatory 24-hour blood pressure monitoring was performed every 6 months over a 5-year period.

The primary end point was the time to a decline of 50% in GFR or progression to end-stage renal disease. A total of 29.9% of the patients in the group that received intensified blood-pressure control reached the primary end point, as compared with 41.7% in the group that received conventional blood-pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P = 0.02). Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50% decrease, despite persistently good blood-pressure control. Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease.

The results of the trial lead to a redefinition of blood pressure targets in children with CKD. The 2016 revision of the European Society of Hypertension guideline for blood pressure management in children recommends a target blood pressure below the 75th percentile in hypertensive children without proteinuria, and below the 50th percentile in those with proteinuria. The 2017 American Academy of Pediatrics guideline even defines the 50th percentile as the recommended blood pressure target for all children with CKD. Hence, the ESCAPE Trial can be considered a true example of a practice-changing clinical trial.

These were the trial investigators: Elke Wühl, Heidelberg, Antonella Trivelli, Genova, Stefano Picca, Rome, Mieczyslaw Litwin, Warsaw, Amira Peco-Antic, Belgrade, Aleksandra Zurowska, Gdansk, Sara Testa, Milano, Augustina Jankauskiene, Vilnius, Sevinc Emre, Istanbul, Alberto Caldas-Afonso, Porto, Ali Anarat, Adana, Patrick Niaudet, Paris, Sevgi Mir, Izmir, Aysin Bakkaloglu, Ankara, Barbara Enke, Hannover, Giovanni Montini, Padova, Ann-Margret Wingen, Essen, Peter Sallay, Budapest, Nikola Jeck, Marburg, Ulla Berg, Stockholm, Salim Caliskan, Istanbul, Simone Wygoda, Leipzig, Katharina Hohbach-Hohenfellner, Mainz, Jiri Dusek, Prague, Tomasz Urasinski, Szeczin, Klaus Arbeiter, Vienna, Thomas Neuhaus, Zurich, Jutta Gellermann, Berlin, Dorota Drozdz, Krakov, Michel Fischbach, Strasbourg, Kristina Müller, Hamburg, Marianne Wigger, Rostock, Licia Peruzzi, Torino, Otto Mehls, Heidelberg, and Franz Schaefer, Heidelberg.

Additional Studies Based on ESCAPE Cohort Data and Biomaterials

 

The ESCAPE cohort has been a rich source of information and biospecimens which fueled numerous post-hoc analyses, biomarker and genetic research. The following publications used data and materials from the ESCAPE cohort:

The following ESCAPE trialists are currently still active in the Network: