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

• ClinicalTrials.gov Identifier: NCT00461734
• Recruitment Status: Completed
• First Posted: April 18, 2007
• Results First Posted: April 25, 2017
• Last Update Posted: April 25, 2017
• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Information provided by (Responsible Party): Medtronic Cardiac Rhythm and Heart Failure

Tracking Information

• First Submitted Date: April 17, 2007
• First Posted Date: April 18, 2007
• Results First Submitted Date: September 15, 2016
• Results First Posted Date: April 25, 2017
• Last Update Posted Date: April 25, 2017
• Study Start Date: August 2007
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2017)

• Change in Left Ventricular Ejection Fraction From Baseline to 2 Years (Intent to Treat Cohort). [ Time Frame: At 2-year follow-up ]
• Change in Left Ventricular Ejection Fraction From Baseline to 2 Years (Per Protocol Cohort). [ Time Frame: At 2-year follow-up ]

• Original Primary Outcome Measures (submitted: April 17, 2007): Comparison of change in Left Ventricular Ejection Fraction at 1 and 2 years between the two patient groups.

Current Secondary Outcome Measures (submitted: March 14, 2017)

• Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Intent to Treat Cohort) [ Time Frame: At 2-year follow-up ]
• Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Per Protocol Cohort) [ Time Frame: At 2-year follow-up ]
• Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Intent to Treat Cohort) [ Time Frame: At 5-years follow-up (study extension) ]
• Incidence of Atrial Tachyarrhythmia Recorded by the Pacemakers (Per Protocol Cohort) [ Time Frame: At 5-year follow-up (study extension) ]
• Worsening of Heart Failure [ Time Frame: At 5-year follow-up (study extension) ]
  Worsening of heart failure can be defined as:

  1. Heart failure-related hospitalization requiring intravenous heart failure therapy, or
  2. Emergency department visit for heart failure requiring intravenous heart failure therapy, or
  3. 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.
  4. CRT-P or CRT-D upgrade.
• All Cause Mortality [ Time Frame: At 5-year follow-up (study extension) ]
• Incidence of Stroke [ Time Frame: At 5-year follow-up (study extension) ]
• Brain Natriuretic Peptide Levels (Intent to Treat Cohort) [ Time Frame: At 2-year follow-up ]
• Brain Natriuretic Peptide Levels (Per Protocol Cohort) [ Time Frame: At 2-year follow-up ]
• Echocardiographic Measures of Left Ventricular Dyssynchrony [ Time Frame: At 2-year follow-up ]
  No analysis has been done for this section since that variable was not collected during the study.
• 6 Minute Hall-Walk Distance (Intent to Treat Cohort) [ Time Frame: At 2-year follow-up ]
• 6 Minute Hall-Walk Distance (Per Protocol Cohort) [ Time Frame: At 2-year follow-up ]

Original Secondary Outcome Measures (submitted: April 17, 2007)

• Incidence of atrial tachyarrhythmia recorded by the pacemakers at 1 and 2 years
• Worsening of heart failure at 1 and 2 years
• All cause mortality at 1 and 2 years
• Incidence of stroke at 1 and 2 years
• Brain Natriuretic Peptide (BNP) levels at 1 and 2 years
• NTproBNP levels at 1 and 2 years
• Echocardiographic measures of cardiac dyssynchrony at 1 and 2 years
• 6 minute walking distances at 1 and 2 years

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PROTECT-PACE STUDY - The Protection of Left Ventricular Function During Right Ventricular Pacing
• Official Title: 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?

Brief Summary

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

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Left Ventricular Dysfunction

Intervention

Other: RV lead placement site

Patients randomised to RV apical or high septal lead placement site

Study Arms

• Active Comparator: RV Apex
  Intervention: Other: RV lead placement site
• Experimental: RV High Septum
  Intervention: Other: RV lead placement site

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 3, 2010): 248
• Original Enrollment (submitted: April 17, 2007): 238
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand, United Kingdom

Administrative Information

• NCT Number: NCT00461734
• Other Study ID Numbers: PROTECT-PACE Version 4
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• Original Responsible Party: Not Provided
• Current Study Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Dr. Gerald Kaye; Princess Alexandra Hospital

• PRS Account: Medtronic Cardiac Rhythm and Heart Failure
• Verification Date: March 2017