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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2005 by Connolly, Stuart, M.D..
Recruitment status was  Not yet recruiting
Sponsor:
Collaborators:
Sanofi
Bristol-Myers Squibb
Information provided by:
Connolly, Stuart, M.D.
ClinicalTrials.gov Identifier:
NCT00225667
First received: September 12, 2005
Last updated: November 22, 2005
Last verified: November 2005
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Hypertension
Drug: Irbesartan
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Connolly, Stuart, M.D.:

Primary Outcome Measures:
  • Time to recurrent AHRE ( 220/min for > 2 minutes)

Secondary Outcome Measures:
  • - 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.

Estimated Enrollment: 200
Study Start Date: December 2005
Estimated Study Completion Date: July 2007
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00225667

Contacts
Contact: Stuart J. Connolly, MD 905-527-4322 ext 44563 connostu@hhsc.ca
Contact: Jeffrey S. Healey, MD 905-527-4322 ext 44789 healeyj@hhsc.ca

Locations
Canada, Ontario
Population Health Research Institute of McMaster University Not yet recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Ellison J. Themeles, MSc.    905-527-4322 ext 44713    themelese@ccc.mcmaster.ca   
Principal Investigator: Stuart J. Connolly, MD         
Sponsors and Collaborators
Connolly, Stuart, M.D.
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00225667     History of Changes
Other Study ID Numbers: 099104, CTA-099104
Study First Received: September 12, 2005
Last Updated: November 22, 2005
Health Authority: Canada: Health Canada

Keywords provided by Connolly, Stuart, M.D.:
Atrial Fibrillation
Arrhythmia
Pacemaker, Artificial
Atrial High Rate Episodes
Electrophysiology
Renin-Angiotensin System
Hypertension
Cardiac Remodeling

Additional relevant MeSH terms:
Atrial Fibrillation
Hypertension
Atrial Remodeling
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Vascular Diseases
Pathological Conditions, Anatomical
Irbesartan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014