Optimised MultiSite Pacing Vector Study

Multimodality Assessment of Acute and Long Term Response to Optimised MultiSite Pacing Cardiac Resynchronisation (MSP CRT) Devices Compared to Biventricular (BiV) CRT, in Patients With Heart Failure

The objective of this clinical investigation is to evaluate the clinical benefits of an MultiSite pacing (MSP) with patient specific left ventricular vector optimization in patients receiving cardiac resynchronization therapy (CRT) after 6 months of therapy.

This clinical investigation is a single-center, prospective, two-arm, randomized 1:1, crossover study designed to evaluate the effectiveness of Optimized MSP CRT compared to conventional bi-ventricular pacing.

Data will be collected at enrolment, CRT implant procedure, hospital pre-discharge, one, three and six months post implant. Enrolment data collection will include demographics, cardiovascular history, medication, echocardiography measurements, heart failure quality of life questionnaire and six minute walk test distance.

CRT implant procedure data collection will include implanted system information, lead location and conduction times. The electrical conduction recording procedure will include surface ECG and device electrogram (EGM) recordings during various MSP vector pacing configurations at the time of CRT device implant.

Patients will also undergo simultaneous invasive pressure measurements using a left ventricular pressure wire to allow haemodynamic measurements (dP/dtmax) during various MSP vector pacing configurations.

Optimal MSP programming settings will be determined by the narrowest QRS duration recorded by 12 lead ECG and the greatest change in dP/dtmax by pressure wires study.

In a subgroup of patients (approximately 25 patients), non-invasive electrical activation data will be collected with electrocardiographic imaging (ECGi) within 45 days of the implant procedure.

Patients will then be randomized 1:1 to receive either standard biventricular pacing or Optimized MSP at their one-month follow-up (± 15 days) visit.

At the 3 months (± 15 days) post randomization follow up visit, data collection will include surface ECG, EGMs, echocardiographic parameters and quality of life questionnaire. The patients will then undergo cross-over to the alternate randomization group with programming adjusted accordingly.

At the final, 6 months (± 15 days) post randomization follow-up visit, data collection will include surface ECG, EGMs, echocardiographic parameters and quality of life questionnaire. This will mark the completion of the study for each patient.

The expected duration of enrolment is 18 months. The total duration of the clinical investigation is expected to be 25 months.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Left Bundle-Branch Block; Systolic Dysfunction
• Intervention / Treatment: Device: Standard biventricular pacing; Device: Optimised MultiSite Pacing

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter H Waddingham, MBBS BSc; Phone Number: 02037658635; Email: p.waddingham@nhs.net
• Study Contact Backup: Name: Victoria Baker, BA; Phone Number: 02037658635; Email: victoria.baker@bartshealth.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital, Barts Health NHS Trust
    • Contact: Peter H Waddingham, MBBS BSc; Phone Number: 02037658635; Email: p.waddingham@nhs.net
    • Contact: Victoria Baker, BA; Phone Number: 02037658635; Email: victoria.baker@bartshealth.nhs.uk
    • Sub-Investigator: Peter H Waddingham, MBBS BSc
    • Principal Investigator: Anthony WC Chow, MBBS BSc MD

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:

• Symptomatic Heart Failure (NYHA class I-IV) with QRS duration of 150ms or more with left bundle branch block and LVEF of 35% or less despite optimal medical therapy.
• Patients above 18 years of age
• Able to provide informed consent and willing to comply with study requirements
• Intrinsic QRS duration ≥ 150 ms
• Sinus (or atrial paced) rhythm with intact AV conduction (PR interval ≤250 ms)

Exclusion Criteria:

• Resting heart rate > 100 bpm
• High degree AV Block (2nd or 3rd degree AV block)
• Documented persistent atrial arrhythmia at the moment of enrolment or patients not likely to remain in sinus (or atrial paced) rhythm for the duration of the study
• Patients scheduled for AV node ablation to treat atrial arrhythmias
• Recent (< 3 months) myocardial infarction, catheter ablation, electrolyte imbalance, or any condition within the last 90 days that would contraindicate CRT programming changes in the opinion of the investigator
• Women who are pregnant or plan to become pregnant during the study course
• Known left ventricular thrombus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Standard biventricular pacing; Cardiac resynchronization therapy (CRT) devices will be programmed as per standard biventricular pacing settings	Device: Standard biventricular pacing; Conventional programming settings using biventricular pacing will be used
ACTIVE_COMPARATOR: Optimised MultiSite Pacing (MSP); Cardiac resynchronization therapy (CRT) devices will be programmed as per optimal MSP programming settings; determined by greatest change in dP/dtmax and narrowest QRS duration.	Device: Optimised MultiSite Pacing; The intervention includes using optimal programming settings with MultiSite pacing configurations via the patient's CRT device. The device in use is the same for each arm, the only changes are the programming settings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiographic clinical response	Response to optimised MSP CRT compared to BiV CRT defined by LV systolic volume reduction of greater than 15% (indicative of "reverse remodelling") at completion of follow up.	3 and 6 months post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute changes in surface ECG QRS duration and morphology	QRS duration changes with CRT programming optimisation	Acute change in QRS duration with pacing compared to intrinsic QRS duration, measured during pacing programming protcol at device implant
Acute change in LV dP/dtmax	Changes in LV contractility as assessed by pressure wire	Acute change in LV dP/dtmax with pacing compared to intrinsic rhythm, measured during pacing programming protcol at device implant
Change in exercise capacity by 6MWT distance	6 minute walk test distance	Pre-implant, 3 and 6 months post randomization
Change in NYHA functional class	New York Heart Association Functional class	Pre-implant, 3 and 6 months post randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sub-group outcome: assessment of LV activation timings with ECGi	Electrocardiographic imaging	1 month post implant

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Anthony WC Chow, MBBS BSc MD, Study Chief Investigator

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2019
• Primary Completion (ANTICIPATED): July 1, 2021
• Study Completion (ANTICIPATED): July 1, 2021

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (ACTUAL): May 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Cardiac Resynchronization Therapy; MultiSite Pacing
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Heart Failure; Bundle-Branch Block
• Other Study ID Numbers: 012604

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No participant data will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes