Effect of Strict Blood Pressure Control and ACE-Inhibition on Progression of Chronic Renal Failure in Pediatric Patients - Full Text View

Sponsor:	University of Heidelberg
Collaborators:	European Commission Boehringer Ingelheim Pharmaceuticals Baxter Healthcare Corporation Aventis Pharmaceuticals
Information provided by:	University of Heidelberg
ClinicalTrials.gov Identifier:	NCT00221845

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Molecular Mechanisms of Disease Progression and Renoprotective Pharmacotherapy in Children With Chronic Renal Failure

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: High Blood Pressure Kidney Failure

Drug Information available for: Ramipril

U.S. FDA Resources

Further study details as provided by University of Heidelberg:

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
Conventional BP Control: Active Comparator 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. 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.
Intensified BP Control: Experimental 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. 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.

Arms

Assigned Interventions

Conventional BP Control: Active Comparator

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.

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.

Intensified BP Control: Experimental

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.

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.

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

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

Show 33 Study Locations

Sponsors and Collaborators

University of Heidelberg

European Commission

Boehringer Ingelheim Pharmaceuticals

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

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Wuhl E, Mehls O, Schaefer F; ESCAPE Trial Group. Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int. 2004 Aug;66(2):768-76.

Jourdan C, Wuhl E, Litwin M, Fahr K, Trelewicz J, Jobs K, Schenk JP, Grenda R, Mehls O, Troger J, Schaefer F. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens. 2005 Sep;23(9):1707-1715.

Litwin M, Wuhl E, Jourdan C, Trelewicz J, Niemirska A, Fahr K, Jobs K, Grenda R, Wawer ZT, Rajszys P, Troger J, Mehls O, Schaefer F. Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol. 2005 May;16(5):1494-500. Epub 2005 Mar 16.

Wuhl E, Hadtstein C, Mehls O, Schaefer F. Ultradian but not circadian blood pressure rhythms correlate with renal dysfunction in children with chronic renal failure. J Am Soc Nephrol. 2005 Mar;16(3):746-54. Epub 2005 Jan 12.

Hadtstein C, Wuhl E, Soergel M, Witte K, Schaefer F. Normative values for circadian and ultradian cardiovascular rhythms in childhood. Hypertension. 2004 Mar;43(3):547-54. Epub 2004 Jan 26.

Wuhl E, Hadtstein C, Mehls O, Schaefer F; Escape Trial Group. Home, clinic, and ambulatory blood pressure monitoring in children with chronic renal failure. Pediatr Res. 2004 Mar;55(3):492-7. Epub 2003 Nov 19.

ESCAPE Trial Group; Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Möller K, Wigger M, Peruzzi L, Mehls O, Schaefer F. Strict blood-pressure control and progression of renal failure in children. N Engl J Med. 2009 Oct 22;361(17):1639-50.

Tabatabaeifar M, Schlingmann KP, Litwin M, Emre S, Bakkaloglu A, Mehls O, Antignac C, Schaefer F, Weber S; ESCAPE Trial Group. Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatr Nephrol. 2009 Dec;24(12):2361-8. Epub 2009 Aug 14.

Gimpel C, Wühl E, Arbeiter K, Drozdz D, Trivelli A, Charbit M, Gellermann J, Dusek J, Jankauskiene A, Emre S, Schaefer F; ESCAPE Trial Group. Superior consistency of ambulatory blood pressure monitoring in children: implications for clinical trials. J Hypertens. 2009 Aug;27(8):1568-74.

Grenda R, Wühl E, Litwin M, Janas R, Sladowska J, Arbeiter K, Berg U, Caldas-Afonso A, Fischbach M, Mehls O, Sallay P, Schaefer F; ESCAPE Trial group. Urinary excretion of endothelin-1 (ET-1), transforming growth factor- beta1 (TGF- beta1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial. Nephrol Dial Transplant. 2007 Dec;22(12):3487-94. Epub 2007 Sep 26.

Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, Caliskan S, Jeck N, Neuhaus TJ, Peco-Antic A, Peruzzi L, Testa S, Mehls O, Wühl E, Schaefer F; ESCAPE Trial Group. Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol. 2007 Feb;18(2):593-8. Epub 2007 Jan 10.

Schönfelder EM, Knüppel T, Tasic V, Miljkovic P, Konrad M, Wühl E, Antignac C, Bakkaloglu A, Schaefer F, Weber S; ESCAPE Trial Group. Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans. Am J Kidney Dis. 2006 Jun;47(6):1004-12.

Matteucci MC, Wühl E, Picca S, Mastrostefano A, Rinelli G, Romano C, Rizzoni G, Mehls O, de Simone G, Schaefer F; ESCAPE Trial Group. Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol. 2006 Jan;17(1):218-26. Epub 2005 Nov 9.

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

Keywords provided by University of Heidelberg:

Ramipril
Hypertension
Chronic renal failure
Disease progression
Left ventricular hypertrophy

Intima media thickness
Cardiovascular disease
Biomarkers
Gene polymorphisms

Additional relevant MeSH terms:

Disease Attributes
Renal Insufficiency
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Vascular Diseases

Disease Progression
Kidney Failure, Chronic
Cardiovascular Diseases
Kidney Diseases
Kidney Failure
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010