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

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?

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.

Study Overview

• Status: Completed
• Conditions: Left Ventricular Dysfunction
• Intervention / Treatment: Other: RV lead placement site

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Princess Alexandra Hospital
    • Brisbane, Queensland, Australia
      • The Prince Charles Hospital
    • Brisbane, Queensland, Australia
      • Royal Brisbane & Womens' Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
    • Adelaide, South Australia, Australia
      • Calvary Wakefield Hospital
    • Adelaide, South Australia, Australia
      • Flinders Medical Center
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
  • Christchurch, New Zealand
    • Christchurch Hospital
• United Kingdom
  • Blackpool, United Kingdom
    • Blackpool Victoria Hospital
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • Colchester, United Kingdom
    • Colchester General
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • St. Thomas' Hospital
  • Middlesbrough, United Kingdom
    • James Cook University Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Orpington, Kent, United Kingdom
    • Princess Royal Hospital
  • Wolverhampton, United Kingdom
    • New Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RV Apex	Other: RV lead placement site; Patients randomised to RV apical or high septal lead placement site
Experimental: RV High Septum	Other: RV lead placement site; Patients randomised to RV apical or high septal lead placement site

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Study Chair: Dr. Gerald Kaye, Princess Alexandra Hospital

Publications and helpful links

General Publications

• Saito M, Iannaccone A, Kaye G, Negishi K, Kosmala W, Marwick TH; PROTECT-PACE investigators. Effect of Right Ventricular Pacing on Right Ventricular Mechanics and Tricuspid Regurgitation in Patients With High-Grade Atrioventricular Block and Sinus Rhythm (from the Protection of Left Ventricular Function During Right Ventricular Pacing Study). Am J Cardiol. 2015 Dec 15;116(12):1875-82. doi: 10.1016/j.amjcard.2015.09.041. Epub 2015 Oct 9.
• Kosmala W, Saito M, Kaye G, Negishi K, Linker N, Gammage M, Marwick TH; Protect-Pace Investigators. Incremental value of left atrial structural and functional characteristics for prediction of atrial fibrillation in patients receiving cardiac pacing. Circ Cardiovasc Imaging. 2015 Apr;8(4):e002942. doi: 10.1161/CIRCIMAGING.114.002942.
• Saito M, Kaye G, Negishi K, Linker N, Gammage M, Kosmala W, Marwick TH; Protect-Pace investigators. Dyssynchrony, contraction efficiency and regional function with apical and non-apical RV pacing. Heart. 2015 Apr;101(8):600-8. doi: 10.1136/heartjnl-2014-306990. Epub 2015 Feb 9.
• Kaye GC, Linker NJ, Marwick TH, Pollock L, Graham L, Pouliot E, Poloniecki J, Gammage M; Protect-Pace trial investigators. Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study. Eur Heart J. 2015 Apr 7;36(14):856-62. doi: 10.1093/eurheartj/ehu304. Epub 2014 Sep 4.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 17, 2007
• First Submitted That Met QC Criteria: April 17, 2007
• First Posted (Estimate): April 18, 2007

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ejection Fraction; Pacemaker; Left Ventricular Dysfunction; Right Ventricular High Septal Pacing; Right Ventricular Apical Pacing; Heart Block
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: PROTECT-PACE Version 4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No