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

• ClinicalTrials.gov Identifier: NCT00225667
• Recruitment Status: Unknown
• First Posted: September 26, 2005
• Last Update Posted: November 23, 2005
• Sponsor: Connolly, Stuart, M.D.
• Collaborators: Sanofi; Bristol-Myers Squibb
• Information provided by: Connolly, Stuart, M.D.

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 26, 2005
• Last Update Posted Date: November 23, 2005
• Study Start Date: December 2005
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: September 12, 2005): Time to recurrent AHRE ( 220/min for > 2 minutes)
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 12, 2005)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Prevention

Condition

• Atrial Fibrillation
• Hypertension

• Intervention: Drug: Irbesartan
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Enrollment (submitted: September 12, 2005): 200
• Original Enrollment: Same as current
• Study Completion Date: July 2007
• Primary Completion Date: Not Provided

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT00225667
• Other Study ID Numbers: 099104; CTA-099104
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Connolly, Stuart, M.D.

Collaborators

• Sanofi
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Stuart J. Connolly, MD; McMaster University
• Principal Investigator: Jeffrey S Healey, MD; McMaster University
• Principal Investigator: Carlos A Morillo, MD; McMaster University
• Principal Investigator: Stefan H Hohnloser, MD; J.W. Goethe University, Frankfurt Germany
• Principal Investigator: Carsten W Israel, MD; J.W. Goethe University, Frankfurt Germany

• PRS Account: Connolly, Stuart, M.D.
• Verification Date: November 2005