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

NCT00232882 | Completed Phase 4

• 1 other identifier: D2452L00003
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hypertension

Keywords

Hypertension; Blood pressure; Antihypertensive drugs; Clinical Pharmacology; Autonomic nervous system; Renin angiotensin system; Oxidative stress; Inflammatory markers

Outcome Measures

Primary Outcomes (1)

• Plasma norepinephrine

  June 2007

Secondary Outcomes (18)

• 1. Seated blood pressure

  June 2007

• 2. 24h ambulatory blood pressure

  June 2007

• 3. Spectral analysis of heart rate (LF, HF, LF/HF)

  June 2007

• 4. Plasma

  December 2007

• a. renin

  december 2007

Study Arms (3)

1

ACTIVE COMPARATOR

Candesartan 16 mg for 4 weeks followed by candesartan 16 mg and hydrochlorothiazide 12.5 mg for 4 weeks

Drug: Candesartan Thiazide

2

ACTIVE COMPARATOR

Atenolol 100 mg for 4 weeks followed by atenolol 100 mg + hydrochlorothiazide 12.5 mg for 4 weeks

Drug: Atenolol Thiazide

3

ACTIVE COMPARATOR

Thiazide 25 mg for 4 weeks then added with Candesartan 16 mg

Drug: Thiazide Candesartan

Interventions

Candesartan Thiazide DRUG

Candesartan 16 mg for 4 weeks then added hydrochlorothiazide for 4 weeks

1

Atenolol Thiazide DRUG

Atenolol 100 mg for 4 weeks followed by atenolol 100 mg + hydrochlorothiazide 12.5 mg for 4 weeks

2

Thiazide Candesartan DRUG

Thiazide 25 mg for 4 weeks then added with Candesartan 16 mg

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• Ability to provide written informed consent.

You may not qualify if:

• Any woman not surgically sterile or menopausal who:
• has a positive urine pregnancy test at screening (Visit 1) or baseline (Visit 3)
• is breast feeding
• Pre-menopausal women (last menstruation \< 1 year prior to start of run-in period) who:
• are not surgically sterile; and/or
• are of child-bearing potential and are NOT practicing acceptable means of birth control.
• Known or suspected secondary hypertension.
• Known reversible or non-reversible obstructive lung disease (e.g. asthma or COPD).
• Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
• ALT or AST greater than 2.0 times the upper limit of reference range;
• Serum creatinine greater than 150 umol/L.
• Uncorrected volume depletion.
• NYHA functional class CHF III-IV (Refer to Appendices).
• Coronary heart disease needing pharmacological therapy.
• Stroke within the preceding six months.

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead
• Ottawa Hospital Research Institute: collaborator

Study Sites (1)

Institut de Recherches Cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

Location

Related Publications (1)

• Johnson NP, Kirkeeide RL, Gould KL. Same Lesion, Different Artery, Different FFR!? JACC Cardiovasc Imaging. 2019 Apr;12(4):718-721. doi: 10.1016/j.jcmg.2017.11.029. Epub 2018 Jan 17. No abstract available.

  PMID: 29361484 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Maxime Lamarre-Cliche, MD

  Institut de Recherches Cliniques de Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 3, 2005
• First Posted: October 5, 2005
• Study Start: December 1, 2003
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: September 4, 2013

Record last verified: 2013-08

Locations

CA (1)