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

Official Title: “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.

Intervention(s) in this Clinical Trial

• 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.
• 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)

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A,AIIA
  • 24 weeks of treatment with Candesartan, where Enalapril is added in the last 8 weeks.
• Active Comparator: A, ACE-I
  • 24 weeks of treatment with Enalapril, where Candesartan is added in the last 8 weeks.
• 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.
• 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)

Primary Measures

• pulse wave velocity (aortic and brachial)
  • Time Frame: 0, 8, 16 and 24 weeks after start of intervention
    Safety Issue?: No

Secondary Measures

• augmentation index
  • Time Frame: 0, 8, 16 and 24 weeks after start of intervention
    Safety Issue?: No
• blood pressure (brachial and aortic)
  • Time Frame: 0, 8, 16 and 24 weeks after start of intervention
    Safety Issue?: No
• buckbergs index
  • Time Frame: 0, 8, 16 and 24 weeks after start of interven
    Safety Issue?: No
• time to reflection
  • Time Frame: 0, 8, 16 and 24 weeks after start of interven
    Safety Issue?: No
• pulse pressure
  • Time Frame: 0, 8, 16 and 24 weeks after start of interven
    Safety Issue?: No
• change in glomerular filtration rate (GFR)
  • Time Frame: 0, 8, 16 and 24 weeks after start of interven
    Safety Issue?: No
• blood parameters
  • Time Frame: at start of intervention and after each 2.5 - 3.week in the study period
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Herlev Hospital Other

Overall Clinical Trial Officials and Contacts

Marie Frimodt-Møller, MD Principal Investigator Dept. of Nephrology, Herlev University Hospital  

Overall Contact: Marie Frimodt-Møller, MD + 45 44 88 44 88 marfri01@heh.regionh.dk

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00235287

Study ID Number: RAS-block study

ClinicalTrials.gov Identifier: NCT00235287

Health Authority: Denmark: National Board of Health