Clinical trial NCT00225667: Irbesartan for the Prevention of Atrial Arrhythmias and Cardiac Electrical Remodeling in Patients With Hypertension and Permanent Pacemakers
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Atrial Fibrillation
Hypertension
Keywords: Atrial Fibrillation
Arrhythmia
Pacemaker, Artificial
Atrial High Rate Episodes
Electrophysiology
Renin-Angiotensin System
Hypertension
Cardiac Remodeling
Lead sponsor: Connolly, Stuart, M.D.
Sponsor class: INDIV
Collaborators: name: Sanofi
name: Bristol-Myers Squibb
First posted: 2005-09-26
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to recurrent AHRE ( 220/min for > 2 minutes)
Secondary outcomes:
measure: - Frequency of AHRE's (> 220/min for > 2 minutes) Evaluated at randomization, month 1 and 6.
measure: - Development of sustained AF (>30 minutes), documented
measure: by ECG, holter, rhythm strip or pacemaker electrograms
measure: - Electrical Remodeling (AERP,SNRT,paced/sensed p-wave
measure: duration). Evaluated at randomization, months 1 and 6.
measure: - Markers of Inflammation (Plasma CRP,TNF-alpha, D-Dimer,
measure: IL-6, Pro-collagen-III products, BNP,MPO,hsP). Blood collection at randomization and month 6.
measure: - Structural Remodeling (left atrial volume, left
measure: ventricular mass, left ventricular diastolic function. Evaluated at randomization and month 6.
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Population Health Research Institute of McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Stuart J. Connolly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Jeffrey S Healey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Carlos A Morillo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J.W. Goethe University, Frankfurt Germany
name: Stefan H Hohnloser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J.W. Goethe University, Frankfurt Germany
name: Carsten W Israel, MD
role: PRINCIPAL_INVESTIGATOR
References: