PROTECT-PACE STUDY - The Protection of Left Ventricular Function During Right Ventricular Pacing

Study Overview
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Brief Summary
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This study will be done in patients who require the implantation of a cardiac pacemaker (an electronic device that controls the heartbeat) for complete heart block (a heart rhythm abnormality resulting in a slow heart beat). Pacemakers regulate the heart beat by delivering pulses of electricity through special wires (pacing leads) which are placed inside the heart. This study will compare two groups of pacemaker patients. Each group will have their pacing leads placed in a particular location in the heart. The purpose of the study is to show whether the position used in one group is better for maintaining effective heart function compared to the position used in the other group. The leads in one group will be placed in a position called the Right Ventricular Apex. This is the traditional and most frequently used position for pacemaker leads. The leads in the other group will be placed in a position called the Right Ventricular High Septum. This is a less commonly used position, but may result in health benefits for the patients compared with the Right Ventricular Apex.

Detailed Description
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There is an increasing amount of evidence to suggest that other positions in the heart may be more effective than the conventional Right Ventricular Apex (RVA) position for restoring good heart function. The best site to place a lead has not yet been proven. This is a study comparing the long term clinical effects of two different lead positions. The measurements taken to assess the clinical effects include: the effectiveness of the heart's pumping action (as measured by ultrasound scans) measurements of how far patients can walk in 6 minutes analysis of blood samples collection of information from the pacemaker about heart rhythm problems Half of the patients in the study will receive conventional leads placed in the more common RVA position in the heart. The other half will receive a relatively new type of lead placed in what is called the Right Ventricular High Septal (RVHS) position. In order to fairly compare the outcomes of these two different lead positions this study has been designed as a 'randomized', 'blind' trial. This means that the group which patients will be entered into will be chosen at random and patients will not be told which group they are in. Patients will each have an equal (50:50) chance of being in either group. By carefully comparing the clinical differences between the two groups of patients, the study aims to prove whether or not there are additional benefits for patients when the RVHS lead position is used. All leads used in the study have been shown to be safe for patients and are available commercially for implantation. All of the implanting doctors involved in the study are experienced at implanting the pacemakers and leads that will be used in this study.

Official Title
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PROTECT-PACE STUDY - The Protection of Left Ventricular Function During Right Ventricular Pacing. Does Right Ventricular High-septal Pacing Improve Outcome Compared With Right Ventricular Apical Pacing?

Conditions
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Left Ventricular Dysfunction

Intervention / Treatment
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* Other: RV lead placement site


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with high grade AV block and sinus rhythm, scheduled to undergo dual chamber pacemaker implantation OR patients with high grade AV block and permanent atrial fibrillation, scheduled to undergo single chamber ventricular pacemaker implantation. Patients aged 18 years or older. Exclusion Criteria: Patients indicated for an Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy. Patients following junctional ablation. Patients with a Myocardial Infarction within three months prior to enrollment. Patients that received bypass surgery within three months prior to enrollment. Patients that had a valve replacement within three months prior to enrollment or patients with a mechanical right heart valve. Patients where a right ventricular lead cannot be placed i.e. complex congenital heart disease. Patients with hypertrophic obstructive cardiomyopathy. Patients with acute coronary syndrome, unstable angina, severe mitral regurgitation and/or hemodynamically significant aortic stenosis. Previous implanted pacemaker or cardioverter defibrillator. Known paroxysmal atrial fibrillation or a documented episode of atrial fibrillation prior to enrollment. Patients on amiodarone therapy within the last six months prior to enrollment. Terminal conditions with a life expectancy of less than two years. Participation in any other study that would confound the results of this study. Psychological or emotional problems that may interfere with the volunteer's ability to provide full consent or fully understand the purposes of the study. Pregnant patients or patients who may become pregnant during the time-scale of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RV Apex<br> | Other: RV lead placement site<br>* Patients randomised to RV apical or high septal lead placement site<br>|
| Experimental: RV High Septum<br> | Other: RV lead placement site<br>* Patients randomised to RV apical or high septal lead placement site<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular Ejection Fraction From Baseline to 2 Years (Intent to Treat Cohort). |  | At 2-year follow-up | 
| Change in Left Ventricular Ejection Fraction From Baseline to 2 Years (Per Protocol Cohort). |  | At 2-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Intent to Treat Cohort) |  | At 2-year follow-up | 
| Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Per Protocol Cohort) |  | At 2-year follow-up | 
| Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Intent to Treat Cohort) |  | At 5-years follow-up (study extension) | 
| Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Per Protocol Cohort) |  | At 5-year follow-up (study extension) | 
| Worsening of Heart Failure | Worsening of heart failure can be defined as: Heart failure-related hospitalization requiring intravenous heart failure therapy, or Emergency department visit for heart failure requiring intravenous heart failure therapy, or Any other visit in which the patient presents with signs or symptoms consistent with heart failure or heart failure exacerbation or marked decline in ejection fraction <35%, and intravenous heart failure therapy is required or titrate therapy. CRT-P or CRT-D upgrade. | At 5-year follow-up (study extension) | 
| All Cause Mortality |  | At 5-year follow-up (study extension) | 
| Incidence of Stroke |  | At 5-year follow-up (study extension) | 
| Brain Natriuretic Peptide Levels (Intent to Treat Cohort) |  | At 2-year follow-up | 
| Brain Natriuretic Peptide Levels (Per Protocol Cohort) |  | At 2-year follow-up | 
| Echocardiographic Measures of Left Ventricular Dyssynchrony | No analysis has been done for this section since that variable was not collected during the study. | At 2-year follow-up | 
| 6 Minute Hall-Walk Distance (Intent to Treat Cohort) |  | At 2-year follow-up | 
| 6 Minute Hall-Walk Distance (Per Protocol Cohort) |  | At 2-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Right Ventricular High Septal Pacing, Right Ventricular Apical Pacing, Left Ventricular Dysfunction, Heart Block, Pacemaker, Atrial Fibrillation, Ejection Fraction