Pulse Wave Velocity, Pulse Wave Morphology and Blocking of the Reninangiotensin System in Patients With Chronic Kidney Disease

Pulse Wave Velocity, Pulse Wave Morphology and Blocking of the Reninangiotensin System in Patients With Chronic Kidney Disease: An Interventional and Methodological Study

The purpose of this study is to determine whether a combination therapy with angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers reduces the arterial stiffness assessed by applantiontonometry more than a single treatment in kidney patients.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Kidney Failure, Chronic
• Intervention / Treatment: Drug: Candesartan and enalapril; Drug: candesartan and enalapril; Drug: candesartan and enalapril; Drug: candesartan and enalapril

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marie Frimodt-Møller, MD; Phone Number: 84878 + 45 44 88 44 88; Email: marfri01@heh.regionh.dk
• Study Contact Backup: Name: Arne H Nielsen, MD, Prof.; Phone Number: 82277 + 45 44 88 44 88; Email: arhn@heh.regionh.dk

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Dept. of Nephrology, Herlev University Hospital
    • Contact: Marie Frimodt-Møller, MD; Phone Number: 84878 + 45 44 88 44 88; Email: marfri01@heh.regionh.dk
    • Contact: Arne H Nielsen, MD, Prof.; Phone Number: 82277 + 45 44 88 44 88; Email: arhn@heh.regionh.dk
    • Principal Investigator: Marie Frimodt-Møller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Creatinine: 150-350 micromol/L
• Blood pressure > 110 systolic
• Negative pregnancy test for fertile women
• Written and oral informed consent from the patient

Exclusion Criteria:

• Treatment with both ACE-inhibitors (ACE-I) and angiotensin receptor blockers
• Pregnancy or breastfeeding
• Treatment with immunosuppressive medication, steroids or non-steroidal anti-inflammatory drugs (NSAIDs)
• Serious chronic heart failure (New York Heart Association [NYHA] III-IV)
• Chronic liver disease
• Suspicion or verified kidney artery stenosis
• Cardiac arrhythmia and/or implanted pacemaker
• Myocardial infarction or cerebrovascular incidence within the last 3 months
• Allergy towards ACE-I or angiotensin receptor blockers
• Amputation of a whole extremity or the crural or femoral part of the leg
• Dementia or a psychological condition that makes understanding of the examination conditions impossible
• Dialysis or renal transplantation
• Treatment with aldosterone antagonists
• Hyperkalemia > 5.5 mmol/l
• Another serious chronic non-renal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A,AIIA; 24 weeks of treatment with Candesartan, where Enalapril is added in the last 8 weeks.	Drug: Candesartan and enalapril; 24 weeks of treatment with Candesartan in incremental doses (4,8,16 mg), where Enalapril is added in incremental doses (5,10 and 20 mg)the last 8 weeks.
Active Comparator: A, ACE-I; 24 weeks of treatment with Enalapril, where Candesartan is added in the last 8 weeks.	Drug: candesartan and enalapril; 24 weeks of treatment with Enalapril in incremental doses (5, 10, 20 mg), where Candesartan is added in incremental doses (4,8,16 mg) in the last 8 weeks.; Drug: candesartan and enalapril; 8 weeks of treatment with Candesartan in incremental doses (4,8,16 mg), followed by 8 weeks of treatment with Enalapril in incremental doses (/5,10,20 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan in incremental doses (4,8,16 mg) and Enalapril 20 mg.; Drug: candesartan and enalapril; 8 weeks of treatment with Enalapril in incremental doses (5,10,20 mg), followed by 8 weeks of treatment with Candesartan (4,8,16 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan 16 mg and Enalapril in incremental doses (5,10,20 mg)
Active Comparator: C, AIIA; 8 weeks of treatment with Candesartan, followed by 8 weeks of treatment with Enalapril. The treatment in the last 8 out of the 24 weeks is a combination of Candesartan and Enalapril.	Drug: candesartan and enalapril; 24 weeks of treatment with Enalapril in incremental doses (5, 10, 20 mg), where Candesartan is added in incremental doses (4,8,16 mg) in the last 8 weeks.; Drug: candesartan and enalapril; 8 weeks of treatment with Candesartan in incremental doses (4,8,16 mg), followed by 8 weeks of treatment with Enalapril in incremental doses (/5,10,20 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan in incremental doses (4,8,16 mg) and Enalapril 20 mg.; Drug: candesartan and enalapril; 8 weeks of treatment with Enalapril in incremental doses (5,10,20 mg), followed by 8 weeks of treatment with Candesartan (4,8,16 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan 16 mg and Enalapril in incremental doses (5,10,20 mg)
Active Comparator: C, ACE; 8 weeks of treatment with Enalapril in incremental doses (5,10,20 mg) , followed by 8 weeks of treatment with Candesartan in incremental doses (4,8,16 mg) . The treatment in the last 8 out of the 24 weeks is a combination of Candesartan 16 mg and Enalapril in incremental doses (5,10,20 mg)	Drug: candesartan and enalapril; 24 weeks of treatment with Enalapril in incremental doses (5, 10, 20 mg), where Candesartan is added in incremental doses (4,8,16 mg) in the last 8 weeks.; Drug: candesartan and enalapril; 8 weeks of treatment with Candesartan in incremental doses (4,8,16 mg), followed by 8 weeks of treatment with Enalapril in incremental doses (/5,10,20 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan in incremental doses (4,8,16 mg) and Enalapril 20 mg.; Drug: candesartan and enalapril; 8 weeks of treatment with Enalapril in incremental doses (5,10,20 mg), followed by 8 weeks of treatment with Candesartan (4,8,16 mg). The treatment in the last 8 out of the 24 weeks is a combination of Candesartan 16 mg and Enalapril in incremental doses (5,10,20 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pulse wave velocity (aortic and brachial)	0, 8, 16 and 24 weeks after start of intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
augmentation index	0, 8, 16 and 24 weeks after start of intervention
blood pressure (brachial and aortic)	0, 8, 16 and 24 weeks after start of intervention
buckbergs index	0, 8, 16 and 24 weeks after start of interven
time to reflection	0, 8, 16 and 24 weeks after start of interven
pulse pressure	0, 8, 16 and 24 weeks after start of interven
change in glomerular filtration rate (GFR)	0, 8, 16 and 24 weeks after start of interven
blood parameters	at start of intervention and after each 2.5 - 3.week in the study period

Collaborators and Investigators

• Sponsor: Herlev Hospital
• Investigators: Principal Investigator: Marie Frimodt-Møller, MD, Dept. of Nephrology, Herlev University Hospital

Publications and helpful links

General Publications

• Frimodt-Moller M, Kamper AL, Strandgaard S, Kreiner S, Nielsen AH. Beneficial effects on arterial stiffness and pulse-wave reflection of combined enalapril and candesartan in chronic kidney disease--a randomized trial. PLoS One. 2012;7(7):e41757. doi: 10.1371/journal.pone.0041757. Epub 2012 Jul 31.

Study record dates

Study Major Dates

• Study Start: September 1, 2005

Study Registration Dates

• First Submitted: October 6, 2005
• First Submitted That Met QC Criteria: October 6, 2005
• First Posted (Estimate): October 10, 2005

Study Record Updates

• Last Update Posted (Estimate): January 19, 2009
• Last Update Submitted That Met QC Criteria: January 16, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: blood pressure; Angiotensin-Converting Enzyme Inhibitors; type 1 angiotensin receptor antagonists
• Additional Relevant MeSH Terms: Urologic Diseases; Cardiovascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enalaprilat; Enalapril; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: RAS-block study