Biopace Study: Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization

Biventricular Pacing for Atrioventricular Block in Left Ventricular Dysfunction to Prevent Cardiac Desynchronization

The primary purpose of the study is to evaluate if patients with a standard indication for permanent ventricular pacing, left ventricular ejection fraction without limit, or any QRS duration will profit from the prevention of ventricular desynchronisation.

Study Overview

• Status: Completed
• Conditions: Ventricular Dysfunction; Atrioventricular Block
• Intervention / Treatment: Device: RV Pacing; Device: Biventricular Pacing

Detailed Description

The study will be performed as a controlled, single-blind, international, multicenter, prospective, randomized, parallel group design.

In order to pragmatically examine the effectiveness of biventricular pacing in patients with an indication for ventricular pacing, the study group with biventricular pacing is compared to a control group with standard pacemakers which only allow univentricular (right ventricular) stimulation, as it has been the standard outside of clinical studies until so far.

• Study Type: Interventional
• Enrollment (Actual): 1833
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Marburg, Germany, 35033
    • Klinikum der Philipps-Universität Marburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Presence of an indication for ventricular pacing according to the actual guidelines for the implantation of cardiac pacemakers and a need for frequent (or even permanent) ventricular pacing for:

   1. Permanent 3rd degree atrioventricular (AV)-block or
   2. Intermittent 3rd degree AV-block in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or
   3. 2nd degree AV-block type Mobitz II in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or
   4. 2nd degree AV-block type Mobitz I (if indicated) in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or
   5. 1st degree AV-block with a pQ-interval ≥ 220 ms and indication for ventricular pacing (includes indication for ventricular pacing based on long HV interval measured during invasive electrophysiological testing) or
   6. Sick-sinus-syndrome with symptomatic sinus bradycardia or sinus arrest as primary indication for device implantation in combination with long 1st degree AV-block with a pQ-interval ≥ 220 ms or
   7. Chronic (permanent) atrial fibrillation (flutter or tachycardia) with a spontaneous heart (ventricular) rate at rest ≤ 60/min or
   8. Chronic (permanent) atrial fibrillation (flutter or tachycardia) with a spontaneous heart (ventricular) rate at rest ≤ 75/min, if initiation or increase of pharmacological treatment with a relevant heart rate lowering effect (negative chronotropic effect) is planned for the time after pacemaker implantation (i.e. ß-blockers for heart failure and rate control)
   9. Patients scheduled for AV node ablation
2. Any QRS duration and morphology
3. Left ventricular ejection fraction (LVEF) without limit as measured by echocardiography (in at least one plane, either 4- or 2-chamber or apical long axis view)
4. Signed written informed consent of the patient or a first-degree relative for study participation after informing the patient/relative about the risks and the aim of the study
5. Willingness and ability to comply with the prescribed follow-up tests and schedule of evaluations.
6. Absence of an implanted ventricular pacing device (patients with atrial pacemakers and new need for ventricular pacing may be included)

Exclusion Criteria:

1. Implanted Cardioverter Defibrillator or consideration for implantation of an ICD due to arrhythmia indication. However, ICD implant for primary prevention of sudden cardiac death in patients with LVEF ≤ 35 % (in accordance with the actual guidelines for the implantation of arrhythmia devices[LVEF < 30%] and in accordance with the results of the SCD-Heft study [LVEF < 35%) will be allowed.
2. Implanted ventricular pacing device
3. Status 1 for cardiac transplantation and likelihood to receive transplantation within 2 years (these patients would not be expected to fulfill the follow-up requirements as outlined in this protocol)
4. Evidence of acute left ventricular dysfunction and high probability for its reversibility (e.g. acute myocarditis, tachycardiomyopathy)
5. Implanted prosthetic tricuspid valve
6. Severe musculoskeletal disorder(s)
7. Age below 18 years
8. Current or planned pregnancy in the next 6 months
9. Current or recent (within the past 30 days) participation in any other clinical investigation
10. Life expectancy of less than 6 months
11. Patient's inability to independently comprehend and complete the Quality of Life (QoL) questionnaire

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: RV Pacing; Standard Pacemaker implant	Device: RV Pacing; Standard Pacemaker implant
EXPERIMENTAL: Biventricular Pacing; Biventricular Pacemaker implant	Device: Biventricular Pacing; Biventricular Pacemaker implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Mortality	Number of deaths observed	Study duration (5.7 years mean follow-up)
Death or Heart Failure Hospitalization	Number of subjects who experienced death or hospitalization where heart failure is a primary cause of hospitalization	Study duration (5.7 years mean follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death Due to Cardiovascular Causes	Number of subjects who died due to cardiovascular causes, as classified by the independent Event Adjudication Committee (IEAC)	Study duration (5.7 years mean follow-up)
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test		12 months post-implant
Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire©	Minnesota Living with Heart Failure (MLWHF) questionnaire score at 12 months MLWHF score: the total scale is from 0 to 105, with higher scores indicating worse health status.	12 months post-implant
Incidence of Hospitalizations for Deterioration of Heart Failure		Study duration (5.7 years mean follow-up)
Incidence of Hospitalizations for Cardiovascular Events		Study duration (5.7 years mean follow-up)
Incidence of Hospitalizations for Any Reason		Study duration (5.7 years mean follow-up)
Cardiac Structure and Function		12 & 24 months
Successful Implantation of the Left Ventricular Lead		Implantation
Chronic Atrial Fibrillation (Defined as Presence of Atrial Fibrillation in Two Subsequent ECG´s/Visits)	Chronic atrial fibrillation is defined as presence of atrial fibrillation in two subsequent ECG´s/visits.	Study duration (5.7 years mean follow-up)
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test		24 months post-implant
Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire©	Minnesota Living with Heart Failure (MLWHF) questionnaire score at 24 months. MLWHF score: the total scale is from 0 to 105, with higher scores indicating worse health status.	24 months post-implant
Duration of Hospitalizations for Deterioration of Heart Failure		Study Duration (5.7 years mean follow-up)
Duration of Hospitalizations for Cardiovascular Events		Study Duration (5.7 years mean follow-up)
Duration of Hospitalizations for Any Reason		Study duration (5.7 years mean follow-up)
Adverse Events Related to Left Ventricular Lead	Only serious adverse events related to the left ventricular lead are included.	Study Duration (5.7 years mean follow-up)

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Principal Investigator: Reinhard Funck, MD, Klinikum Bad Hersfeld, Germany; Study Chair: Jean-Jacques Blanc, Prof., Hôpital Cavale Blanche, Brest, France

Publications and helpful links

General Publications

• Funck RC, Blanc JJ, Mueller HH, Schade-Brittinger C, Bailleul C, Maisch B; BioPace Study Group. Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the 'Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)' study. Europace. 2006 Aug;8(8):629-35. doi: 10.1093/europace/eul075.
• Funck RC, Mueller HH, Lunati M, Piorkowski C, De Roy L, Paul V, Wittenberg M, Wuensch D, Blanc JJ; BioPace study group. Characteristics of a large sample of candidates for permanent ventricular pacing included in the Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization Study (BioPace). Europace. 2014 Mar;16(3):354-62. doi: 10.1093/europace/eut343. Epub 2013 Nov 7.

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 16, 2005

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Standard pacing indication
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Ventricular Dysfunction; Atrioventricular Block
• Other Study ID Numbers: CR03006HF

Drug and device information, study documents

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