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

Study Overview
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Brief Summary
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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.

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

Conditions
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Kidney Failure, Chronic, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Candesartan and enalapril
* Drug: candesartan and enalapril
* Drug: candesartan and enalapril
* Drug: candesartan and enalapril


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A,AIIA<br>24 weeks of treatment with Candesartan, where Enalapril is added in the last 8 weeks. | Drug: Candesartan and enalapril<br>* 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.<br>|
| Active Comparator: A, ACE-I<br>24 weeks of treatment with Enalapril, where Candesartan is added in the last 8 weeks. | Drug: candesartan and enalapril<br>* 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.<br>|
| Active Comparator: C, AIIA<br>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<br>* 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.<br>|
| Active Comparator: C, ACE<br>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<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiotensin-Converting Enzyme Inhibitors, type 1 angiotensin receptor antagonists, blood pressure