Effect of Strict Blood Pressure Control and ACE-Inhibition on Progression of Chronic Renal Failure in Pediatric Patients (ESCAPE)

This study has been completed.
Sponsor:
Collaborators:
European Commission
Boehringer Ingelheim
Baxter Healthcare Corporation
Aventis Pharmaceuticals
Information provided by:
Heidelberg University
ClinicalTrials.gov Identifier:
NCT00221845
First received: September 15, 2005
Last updated: January 11, 2010
Last verified: January 2010
  Purpose

In children with chronic kidney disease, progression to end-stage renal failure is associated with high patient morbidity and poor quality of life. In adults, inhibition of the renin angiotensin system (RAS) slows down the rate of renal failure progression. This concept is as yet unproven in children, in whom chronic renal failure (CRF) is more commonly due to hypo/dysplastic malformations than to acquired glomerulopathies as typical for adult chronic kidney disease. The current project aims at assessing the genetic and molecular mechanisms and cardiovascular consequences of progressive CRF and to develop a strategy of pharmacological renoprotection in children.


Condition Intervention Phase
Children
Chronic Renal Failure
Hypertension
Acquired Kidney Disease
Congenital Kidney Disease
Drug: ACE Inhibition
Drug: Intensified Blood Pressure Control
Drug: Add-on Angiotensin Receptor Blockade
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Mechanisms of Disease Progression and Renoprotective Pharmacotherapy in Children With Chronic Renal Failure

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Time interval to renal 'loss' as defined by an absolute decrease in creatinine clearance by 50 % or attainment of renal replacement therapy. [ Time Frame: two-monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of treatment on urinary protein excretion [ Time Frame: two-monthly ] [ Designated as safety issue: No ]
  • Effect of treatment on blood pressure [ Time Frame: two-monthly ] [ Designated as safety issue: No ]
  • Safety of treatment [ Time Frame: initially weekly, than two-monthly ] [ Designated as safety issue: Yes ]

Enrollment: 400
Study Start Date: January 1998
Study Completion Date: January 2010
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Conventional BP Control
Targeted 24-hour mean arterial pressure will be the 50th-95th percentile for age.
Drug: ACE Inhibition
ACE inhibitor ramipril (6 mg/m²/day) will be given to all subjects.
Other Name: Delix
Drug: Intensified Blood Pressure Control
Any antihypertensive drugs except ACE inhibitors and angiotensin receptor blockers will be allowed.
Drug: Add-on Angiotensin Receptor Blockade
In patients who show persistent or breakthrough proteinuria at the end of the initial study period, telmisartan (50 mg/m²/day) will be added to the existing medication.
Other Name: Micardis
Experimental: Intensified BP Control
Targeted 24-hour mean arterial pressure will be the 5th to 50th percentile for age.
Drug: ACE Inhibition
ACE inhibitor ramipril (6 mg/m²/day) will be given to all subjects.
Other Name: Delix
Drug: Intensified Blood Pressure Control
Any antihypertensive drugs except ACE inhibitors and angiotensin receptor blockers will be allowed.
Drug: Add-on Angiotensin Receptor Blockade
In patients who show persistent or breakthrough proteinuria at the end of the initial study period, telmisartan (50 mg/m²/day) will be added to the existing medication.
Other Name: Micardis

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 3-18 years
  • Moderate state of renal failure (creatinine clearance 15 - 75 ml / min / 1.73 m²)
  • Mean arterial blood pressure (ABPM) > 50.percentile and/or antihypertensive treatment
  • Written informed consent

Exclusion Criteria:

  • Age <3 years or >18 years at start of study
  • Unstable clinical condition (vomiting, anorexia, etc) or superimposed important disease
  • Unilateral or bilateral renal artery stenosis
  • Urological surgery possibly affecting renal function expected during study period
  • Insufficient compliance with prescribed antihypertensive medication during the run-in period
  • Secondary renal diseases such as lupus, amyloidosis and primary hyperoxaluria, and patients treated with immunosuppressive agents (including corticosteroids)
  • Severe primary cardiac disease, hepatic insufficiency and malabsorption syndrome
  • Erythropoietin or growth hormone therapy with a duration of less than 3 months prior to run-in period
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00221845

  Show 33 Study Locations
Sponsors and Collaborators
Heidelberg University
European Commission
Boehringer Ingelheim
Baxter Healthcare Corporation
Aventis Pharmaceuticals
Investigators
Principal Investigator: Franz Schaefer, MD University of Heidelberg, Children's Hospital
Principal Investigator: Otto Mehls, MD University of Heidelberg, Children's Hospital
  More Information

Publications:

Responsible Party: Prof. Dr. med. Dr. hc. Franz Schaefer, University Hospital for Pediatric and Adolescent Medicine
ClinicalTrials.gov Identifier: NCT00221845     History of Changes
Other Study ID Numbers: QLRT-2001-00908
Study First Received: September 15, 2005
Last Updated: January 11, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heidelberg University:
Ramipril
Hypertension
Chronic renal failure
Disease progression
Left ventricular hypertrophy
Intima media thickness
Cardiovascular disease
Biomarkers
Gene polymorphisms

Additional relevant MeSH terms:
Hypertension
Kidney Diseases
Disease Progression
Renal Insufficiency
Kidney Failure, Chronic
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Disease Attributes
Pathologic Processes
Renal Insufficiency, Chronic

ClinicalTrials.gov processed this record on September 30, 2014