Pharmacodynamic Influences of Candesartan, Atenolol, Hydrochlorothiazide and Drug Combinations in Hypertensive Patients.

• Status: Completed
• Trial end date: 2006-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Angiotensin receptor antagonists (ARA), beta-blockers and diuretics do not seem to confer equivalent cardiovascular protection in hard outcomes clinical trials (beta blockers inferior). These results may be explained by differences in their effects on sympathetic activity, oxidative stress, inflammation and renin angiotensin system activation.

How diuretic addition to first line therapy with ARAs and beta-blockers modulates neurohumoral and hemodynamic parameters is not well understood.

The main hypothesis of this study is that an ARA (candesartan) combined or not with a diuretic will not increase sympathetic activity as much as a beta blocker (atenolol). Secondary hypothesis are of similar nature but relate to hemodynamic parameters, oxidative stress markers, inflammatory markers, or the renin angiotensin system.

The main objective of this study is to assess and compare the effects of candesartan and atenolol and their combination with low dose diuretic therapy on the autonomic nervous system, hemodynamic parameters,on oxidative stress, on inflammatory markers, and on the renin-angiotensin system.

Protocol sponsored by Astra Zeneca canada

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborator: Ottawa Hospital Research Institute
• Treatments: Atenolol; Candesartan; Candesartan cilexetil; Hydrochlorothiazide; Sodium Chloride Symporter Inhibitors

Criteria

Inclusion Criteria:

1. Mild to moderate essential hypertension as defined by a morning mean DBP *90 mmHg and

• 109 mm Hg, a mean SBP * 200 mm H for two consecutive visits (Visits 2 and 3) during the two-to-four week placebo run-in period,

2. Ability to provide written informed consent.

Exclusion Criteria:

1. Any woman not surgically sterile or menopausal who:

1. has a positive urine pregnancy test at screening (Visit 1) or baseline (Visit 3)

2. is breast feeding

2. Pre-menopausal women (last menstruation < 1 year prior to start of run-in period) who:

1. are not surgically sterile; and/or

2. are of child-bearing potential and are NOT practicing acceptable means of birth control.

3. Known or suspected secondary hypertension.

4. Known reversible or non-reversible obstructive lung disease (e.g. asthma or COPD).

5. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

1. ALT or AST greater than 2.0 times the upper limit of reference range;

2. Serum creatinine greater than 150 umol/L.

6. Uncorrected volume depletion.

7. NYHA functional class CHF III-IV (Refer to Appendices).

8. Coronary heart disease needing pharmacological therapy.

9. Stroke within the preceding six months.

10. PTCA within the preceding three months.

11. History of angioedema.

12. Clinically significant sinus bradycardia below 55 beats/min. at randomization.

13. Sustained ventricular tachycardia, atrial fibrillation, or other clinically relevant cardiac arrhythmias as determined by the clinical Investigator.

14. Second or third degree AV block, left bundle branch block or any clinically relevant conduction abnormality as determined by the clinical Investigator.

15. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve.

16. Administration of digoxin.

17. Patients with a fasting glucose > 7.0.

18. Use of antihypertensive agents such as diuretics, ACE inhibitors, angiotensin II antagonists, *- blockers, *-blockers, calcium channel antagonists, direct vasodilators that cannot be stopped for the trial.

19. Administration of other non-antihypertensive medications known to affect blood pressure (e.g., oral corticosteroids, MAO inhibitors, nitrates) at any time during the trial.

20. Chronic use of salt substitutes containing potassium chloride; potassium supplements; extreme dietary restrictions.

21. Uncorrected sodium depletion as defined by a serum sodium level less than 135 mEq/L.

22. Clinically significant hyperkalemia as defined by serum potassium level greater than 5.2 mEq/L. Clinically significant hypokalemia as defined by serum potassium level less than 3.0 mEq/L.

23. Patients receiving any investigational therapy within one month of signing the informed consent form.

24. Known hypersensitivity to any component of candesartan, atenolol or hydrochlorothiazide.

25. Any other clinical condition which, in the opinion of the principal Investigator, would not allow safe completion of the protocol and safe administration of trial medication.

26. Known for allergy to sulfa or heparin

27. Blood donation in the preceding 2 months