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Effects of Preferential Left Ventricular Pacing on Ventriculoarterial Coupling and Clinical Course of Heart Failure (READAPT)

Primary Purpose

Heart Failure With Reduced Ejection Fraction

Status

Not yet recruiting

Phase

Not Applicable

Locations

Greece

Study Type

Interventional

Intervention

Preferential left ventricular pacing

Biventricular pacing

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring Heart failure, Cardiac resynchronization therapy, Preferential left ventricular pacing, Ventriculoarterial coupling, Echocardiography, Cardiopulmonary exercise test

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18-80 years old Provided informed consent Any cardiomyopathy type, diagnosed at least 6 months prior (to exclude recent myocarditis cases that may remit and confound outcomes) On optimal medical therapy for at least 3 months, An existing I/IIa indication for a CRT-D device Both new CRT-D implantation and an upgrade from an existing ICD or pacemaker with no prior left ventricular lead placement.

Exclusion Criteria:

Have an existing Class I recalled lead,
Are anticipated to need heart transplantation within the next 9 months,
Have undergone cardiac transplantation less than 40 days prior to enrolment,
Have had a cerebrovascular accident or transient ischemic attack within 3 months of enrollment,
Have had a recent myocardial infarction less than 40 days prior to enrollment, or unstable angina or cardiac revascularization less than 3 months prior to enrolment,
Have documented moderate to severe/severe mitral/aortic/tricuspid/pulmonary insufficiency (noninvasive VAC calculation impossible),
Exhibit a daily burden of premature ventricular complexes (PVCs) of either ≥10% of total QRSs or ≥10,000 on ambulatory ECG recording21, 22 (to exclude PVC-related, potentially reversible cardiomyopathy),
Are currently participating in a clinical investigation that includes an active treatment arm,
Have diagnosed pulmonary hypertension other than class II (left heart-related),
Have known stage IV-V renal dysfunction (clearance estimated by the Cockcroft-Gault equation),
Have permanent atrial fibrillation,
Have complete atrioventricular block,
Have a prolonged (>200msec) PQ interval on surface ECG (thus invalidating the option for preferential LV pacing),
Are pregnant or planning to become pregnant during the duration of the study (in case of unplanned pregnancy the patient will have to be excluded from the study),
Have an expected life expectancy of <12 months, or
Undergo major adaptations to their pharmacological regimens during follow-up (e.g. initiation of neprilysin inhibitors).

Sites / Locations

First University Department of Cardiology, Hippokrateion General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Classical biventricular pacing

Preferential left ventricular pacing

Arm Description

Commercially available LV-pacing capable CRT devices and quadripolar leads will be implanted. Right ventricular (RV) and right atrial (RA) leads will be placed according to standard practice. The LV lead will also be placed according to standard practice, targeting to a lateral, posterolateral, or anterolateral branch of the coronary sinus (CS). Interventricular delay programmed will be determined based on stroke volume maximization, and will be used as a criterion for BVP optimization. Atrioventricular delay optimization shall be automatically performed by the device.

In G2 patients, an algorithm for preferential left ventricular pacing will be activated. Following selection of the dipole maximizing stroke volume during simultaneous LV-RV pacing, subsequent V-V delay optimization shall be delegated to the algorithm. Based on previous studies, a subgroup analysis of G2 will be performed, comparing those receiving ≥50% with those receiving <50% preferential LV pacing evaluated over the total duration of the study (12 months).

Outcomes

Primary Outcome Measures

Changes in patient exercise capacity

Assessed by cardiopulmonary exercise test in terms of maximal oxygen consumption in ml/kg/min

Secondary Outcome Measures

Number of hospitalizations for heart failure

Data retrieved from online patient file will be used to compare number of unplanned hospitalizations for worsening heart failure between groups

Left ventricular function

Assessed by ejection fraction (in %), strain echocardiography - changes in % global longitudinal peak strain and diastolic function indices (E/e')

Right ventricular function

Assessed by strain echocardiography in terms of two-dimensional % global longitudinal peak strain

Ventriculoarterial coupling for both systemic and pulmonary circulation

Assessed by the noninvasive single-beat echocardiographic method in terms of distance from 1 (value associated with maximization of stroke work for a given contractility)

Full Information

NCT ID

NCT04420065

First Posted

June 1, 2020

Last Updated

June 3, 2020

Sponsor

National and Kapodistrian University of Athens

1. Study Identification

Unique Protocol Identification Number

NCT04420065

Brief Title

Effects of Preferential Left Ventricular Pacing on Ventriculoarterial Coupling and Clinical Course of Heart Failure

Acronym

READAPT

Official Title

CompaRative Study of the Effects of Left ventriculAr and Biventricular Pacing on inDices of cArdiac Function and Clinical Course of Heart Failure PatienTs: Rationale and Design of the READAPT Randomized Trial

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 1, 2020 (Anticipated)

Primary Completion Date

September 1, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National and Kapodistrian University of Athens

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Randomized trial of adult patients to study the effects of preferential left ventricular pacing on ventriculoarterial coupling of both systemic and pulmonary circulation, indices of systolic and diastolic function of both ventricles, and clinical course of patients with advances dyssynchronous heart failure.

Detailed Description

Study hypothesis is that preferential left ventricular (LV) pacing, delivered by means of the AdaptivCRT® algorithm and in conjunction with automated V-V delay adjustments, will lead to improvements over standard biventricular pacing (BVP) in the function of all cardiac chambers, reduce arrhythmic burden, improve ventricular-arterial coupling (VAC), and patient functional status. It would be interesting to study what changes in right-side VAC (RVAC) can be appreciated with the activation of the preferential LV pacing algorithm and how they relate to each other, i.e. whether LV is driven towards maximizing output whilst RV shifts to optimizing energy efficiency. READAPT is a single-center, prospective, randomized trial of heart failure patients eligible for CRT according to current European heart failure guidelines. Informed written consent is required from all study participants. Adult (aged 18-80 years old), consenting patients with any cardiomyopathy type, diagnosed at least 6 months prior (to exclude recent myocarditis cases that may remit and confound outcomes), on optimal medical therapy for at least 3 months, and an existing I/IIa indication for a cardiac resynchronization therapy - defibrillator (CRT-D) device will be enrolled and randomized into 2 groups, one receiving standard CRT (Group 1 - G1), and one with activation of the preferential LV pacing algorithm (Group 2 - G2). Enrollment date will amount to the baseline assessment date, with device implantation occurring preferably within 48 hours. READAPT will include patients with both new CRT-D implantation and an upgrade from an existing defibrillator or pacemaker with no prior left ventricular lead placement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure With Reduced Ejection Fraction

Keywords

Heart failure, Cardiac resynchronization therapy, Preferential left ventricular pacing, Ventriculoarterial coupling, Echocardiography, Cardiopulmonary exercise test

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Patients randomized after enrollment to receive either standard biventricular pacing, or preferential left ventricular pacing (left ventricle will be resynchronized, but right ventricle will be activated through the intrinsic conduction system)

Masking

ParticipantOutcomes Assessor

Masking Description

Patient and assessor unaware of chosen programming mode and activated algorithms. The standard of care that is biventricular pacing will be provided to all participants.

Allocation

Randomized

Enrollment

220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Classical biventricular pacing

Arm Type

Active Comparator

Arm Description

Arm Title

Preferential left ventricular pacing

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Preferential left ventricular pacing

Intervention Description

Activation of an algorithm attempting to provide preferential left ventricular pacing in an anticipatory manner, thus potentially preventing iatrogenic, pacing-related, right ventricular dysfunction, and improving coupling and outcomes in dyssynchronous heart failure patients

Intervention Type

Device

Intervention Name(s)

Biventricular pacing

Intervention Description

Standard biventricular pacing, with V-V delay programmed based on stroke volume maximization, and A-V delay delegated to the device

Primary Outcome Measure Information:

Title

Changes in patient exercise capacity

Description

Assessed by cardiopulmonary exercise test in terms of maximal oxygen consumption in ml/kg/min

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Number of hospitalizations for heart failure

Description

Data retrieved from online patient file will be used to compare number of unplanned hospitalizations for worsening heart failure between groups

Time Frame

12 months

Title

Left ventricular function

Description

Assessed by ejection fraction (in %), strain echocardiography - changes in % global longitudinal peak strain and diastolic function indices (E/e')

Time Frame

12 months

Title

Right ventricular function

Description

Assessed by strain echocardiography in terms of two-dimensional % global longitudinal peak strain

Time Frame

12 months

Title

Ventriculoarterial coupling for both systemic and pulmonary circulation

Description

Assessed by the noninvasive single-beat echocardiographic method in terms of distance from 1 (value associated with maximization of stroke work for a given contractility)

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-80 years old Provided informed consent Any cardiomyopathy type, diagnosed at least 6 months prior (to exclude recent myocarditis cases that may remit and confound outcomes) On optimal medical therapy for at least 3 months, An existing I/IIa indication for a CRT-D device Both new CRT-D implantation and an upgrade from an existing ICD or pacemaker with no prior left ventricular lead placement. Exclusion Criteria: Have an existing Class I recalled lead, Are anticipated to need heart transplantation within the next 9 months, Have undergone cardiac transplantation less than 40 days prior to enrolment, Have had a cerebrovascular accident or transient ischemic attack within 3 months of enrollment, Have had a recent myocardial infarction less than 40 days prior to enrollment, or unstable angina or cardiac revascularization less than 3 months prior to enrolment, Have documented moderate to severe/severe mitral/aortic/tricuspid/pulmonary insufficiency (noninvasive VAC calculation impossible), Exhibit a daily burden of premature ventricular complexes (PVCs) of either ≥10% of total QRSs or ≥10,000 on ambulatory ECG recording21, 22 (to exclude PVC-related, potentially reversible cardiomyopathy), Are currently participating in a clinical investigation that includes an active treatment arm, Have diagnosed pulmonary hypertension other than class II (left heart-related), Have known stage IV-V renal dysfunction (clearance estimated by the Cockcroft-Gault equation), Have permanent atrial fibrillation, Have complete atrioventricular block, Have a prolonged (>200msec) PQ interval on surface ECG (thus invalidating the option for preferential LV pacing), Are pregnant or planning to become pregnant during the duration of the study (in case of unplanned pregnancy the patient will have to be excluded from the study), Have an expected life expectancy of <12 months, or Undergo major adaptations to their pharmacological regimens during follow-up (e.g. initiation of neprilysin inhibitors).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Christina Chrysohoou, MD PhD

Phone

00306944435168

chrysohoou@usa.net

First Name & Middle Initial & Last Name or Official Title & Degree

Christos-Konstantinos Antoniou, MD PhD

Phone

00306972708430

ckantoniou@hotmail.gr

Facility Information:

Facility Name

First University Department of Cardiology, Hippokrateion General Hospital

City

Athens

State/Province

Attica

ZIP/Postal Code

11527

Country

Greece

Facility Contact: