Irbesartan for the Prevention of Atrial Arrhythmias and Cardiac Electrical Remodeling in Patients With Hypertension and Permanent Pacemakers

Hypertension Clinical Trial

Official title:

Irbesartan for the Prevention of Atrial Arrhythmias and Cardiac Electrical Remodeling in Patients With Hypertension, Permanent Pacemakers and Risk Factors for Developing Atrial Fibrillation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00225667
• Other study ID #: 099104
• Secondary ID: CTA-099104
• Status: Not yet recruiting
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: November 22, 2005
• Start date: December 2005
• Est. completion date: July 2007

Study information

• Verified date: November 2005
• Source: Connolly, Stuart, M.D.
• Contact: Stuart J. Connolly, MD
• Phone: 905-527-4322
• Email: connostu[@]hhsc.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether irbesartan will reduce the rate of recurrent atrial high rate episodes and the development of clinical sustained atrial fibrillation in patients with hypertension and permanent pacemaker.

Description:

Patients with permanent pacemakers have a high risk of atrial fibrillation (AF), particularly those with hypertension, sinus node dysfunction, and those with short episodes of atrial arrhythmias, known as atrial high-rate episodes (AHRE). AHRE are felt to be a precursor to AF, and may be both the result and a cause of changs in the atrial electrophysiology, and structure (known as cardiac remodeling)that are associated with the development of AF.

Evaluating this process in human AF has been limited by the cumbersome nature of performing serial, invasive electrophysiologic studies. However, modern pacemakers now permit rapid, non-invasive electrophysiologic testing and can also accurately document AHRE, which allows the convenient study of therapy aimed at preventing the progression from AHRE to overt AF. In addition, this group of patients also affords the ability to evaluate the recurrence of AHRE on the progression of structural and electrical remodeling.

Comparison: Irbesartan compared to placebo.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Sinus Node Dysfunction (with or without AV conduction disturbance)

• Permanent, atrial or dual-chamber pacemaker implanted > 2 months before enrollment and with ability to record and store atrial high-rate episodes, frequency of mode switches and to perform non-invasive electrophysiologic testing

• History of at least 6 AHRE in the last 6 months (rate > 220/min, duration of > 2 minutes

• History of prior diagnosis of hypertension and/or treated for hypertension OR two documented BP > 130/85 (measurements done at least one week apart)

Exclusion Criteria:

• Permanent or persistent AF or more than 6 episodes of symptomatic paroxysmal AF in the previous 6 months

• Documented Cr >200 umol/L and K+ >5.2 mmol/L in the previous 3 months

• Current treatment with a potassium sparing diuretic, unless serum potassium known to be in the normal range

• LV ejection fraction known to be < 40 %

• Moderate or severe mitral regurgitation (3+, 4 +)

• Mitral stenosis of more than mild severity

• Aortic stenosis with mean gradient of > 25 mmHg

• Angina at rest in the last 2 months, or current CCS Class 3 or 4 angina

• Unipolar atrial lead

• Previous AV node ablation

• P-wave amplitude less than 1.5 mV

• Current therapy with an ACE inhibitor, ARB or aldosterone antagonist

• Current or planned (within 6 months) with an anti-arrhythmic medication (amiodarone, sotalol, flecainide, propafenone, quinidine, dofetilide

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Remodeling
• Hypertension

Intervention

Drug:
• Irbesartan

Locations

Country	Name	City	State
Canada	Population Health Research Institute of McMaster University	Hamilton	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Connolly, Stuart, M.D.	Bristol-Myers Squibb, Sanofi

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to recurrent AHRE ( 220/min for > 2 minutes)
Secondary	- Frequency of AHRE’s (> 220/min for > 2 minutes) Evaluated at randomization, month 1 and 6.
Secondary	- Development of sustained AF (>30 minutes), documented
Secondary	by ECG, holter, rhythm strip or pacemaker electrograms
Secondary	- Electrical Remodeling (AERP,SNRT,paced/sensed p-wave
Secondary	duration). Evaluated at randomization, months 1 and 6.
Secondary	- Markers of Inflammation (Plasma CRP,TNF-alpha, D-Dimer,
Secondary	IL-6, Pro-collagen-III products, BNP,MPO,hsP). Blood collection at randomization and month 6.
Secondary	- Structural Remodeling (left atrial volume, left
Secondary	ventricular mass, left ventricular diastolic function. Evaluated at randomization and month 6.