AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

Sponsor

Universitaire Ziekenhuizen Leuven (Other)

Overall Status

Recruiting

CT.gov ID

NCT04225520

Collaborator

(none)

700

Enrollment

Locations

Arms

71.7

Anticipated Duration (Months)

53.8

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Previous experience with cardiac resynchronization therapy (CRT) candidates suggests that selection of these patients can be improved. Current clinical guideline approaches are mainly too unspecific and lead to a high non-responder rate of 30-40%, which causes a burden on health care systems and puts patients at risk of an unnecessary treatment who might benefit more from a conservative approach. Previous work indicated that using the assessment of mechanical dyssynchrony on echocardiography can lower the non-responder rate at least by 50% without compromising sensitivity for detecting amendable patients. The current prospective, randomized, multi-center trial was therefore designed to prove that the characterization of the mechanical properties of the left ventricle can improve patient selection for CRT. Patients will be randomized into one of two study arms: a control study arm with treatment recommendation based on clinical guidelines criteria, or an experimental study arm with treatment recommendation based on the presence of mechanical dyssynchrony. All patients will receive a CRT implantation. In the control study arm, bi-ventricular pacing will be turned on. In the experimental study arm, bi-ventricular pacing will be turned on or off, depending on the presence or absence of mechanical dyssynchrony, respectively. The primary endpoint will be non-inferiority in outcome of a treatment recommendation based on mechanical dyssynchrony, achieved with a lower number of CRT devices implanted, effectively leading to a lower number needed to treat. Outcome measures are the average relative change in continuously measured LVESV per arm and the percentage 'worsened' according to the Packer Clinical Composite Score per arm after 1 year follow-up.

Condition or Disease	Intervention/Treatment	Phase
Left Ventricular Dyssynchrony Heart Failure Cardiomyopathy, Dilated Cardiac Remodeling, Ventricular	Device: Cardiac resynchronization therapy ON Device: Cardiac resynchronization therapy OFF	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment recommendation based on guidelines Treatment of the patient assigned to this arm will be based on the current guidelines for CRT implantation, as issued by the European Society of Cardiology. All patients will receive CRT implantation, with bi-ventricular pacing ON.	Device: Cardiac resynchronization therapy ON Implantation of a CRT device. Bi-ventricular pacing will be turned ON.
Experimental: Treatment recommendation based on mechanical dyssynchrony Treatment of the patients assigned to this arm will be based on the presence of mechanical dyssynchrony. All patients will receive CRT implantation. Bi-ventricular pacing will be either turned ON or OFF, based on respectively the presence or absence of mechanical dyssynchrony.	Device: Cardiac resynchronization therapy ON Implantation of a CRT device. Bi-ventricular pacing will be turned ON. Device: Cardiac resynchronization therapy OFF Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.

Arm

Intervention/Treatment

Active Comparator: Treatment recommendation based on guidelines

Treatment of the patient assigned to this arm will be based on the current guidelines for CRT implantation, as issued by the European Society of Cardiology. All patients will receive CRT implantation, with bi-ventricular pacing ON.

Device: Cardiac resynchronization therapy ON

Implantation of a CRT device. Bi-ventricular pacing will be turned ON.

Experimental: Treatment recommendation based on mechanical dyssynchrony

Treatment of the patients assigned to this arm will be based on the presence of mechanical dyssynchrony. All patients will receive CRT implantation. Bi-ventricular pacing will be either turned ON or OFF, based on respectively the presence or absence of mechanical dyssynchrony.

Device: Cardiac resynchronization therapy ON

Implantation of a CRT device. Bi-ventricular pacing will be turned ON.

Device: Cardiac resynchronization therapy OFF

Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.

Outcome Measures

Primary Outcome Measures

Volume response and Packer Clinical Composite Score [12 months follow-up]
Non-inferiority in outcome of a treatment recommendation based on mechanical dyssynchrony, achieved with a lower number of CRT devices implanted, effectively leading to a lower number needed to treat. Outcome measures are the average relative change in continuously measured left ventricular end-systolic volume per arm and the percentage 'worsened' according to the Packer Clinical Composite Score per arm after 12 months follow-up

Secondary Outcome Measures

Effect on left ventricular function in both arms [12 months follow-up]
≥ 10% difference in relative change in left ventricular ejection fraction and/or ≥1.5% difference in absolute change in global longitudinal strain and/or improvement in myocardial work from baseline to month 12
Difference in quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms [12 months follow-up]
≥ 5 points difference in change on the Minnesota Living with Heart Failure questionnaire score and/or ≥0.08 points difference in change on the EuroQol 5D index score from baseline to month 12
Difference in 6 minute walk test distance in both arms [12 months follow-up]
≥ 45 meters difference in change from baseline to month 12
Difference in predictive value for volume response [12 months follow-up]
≥15% relative reduction in left ventricular end-systolic volume from baseline to month 12 will be considered as a response
Difference in predictive value for long-term patient outcome in both arms [1 year, 3 years and 5 years follow-up]
Cox's proportional hazards model: At 1 year for 'worsened' PCCS At 3 and 5 years for cardiovascular mortality and heart failure hospitalization
Difference in long-term patient outcome in both arms [3 years and 5 years follow-up]
Kaplan Meier survival analysis for heart failure hospitalization Kaplan Meier survival analysis for cardiovascular mortality Kaplan Meier survival analysis for combined heart failure hospitalization and cardiovascular mortality Kaplan Meier survival analysis for all-cause mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The proposed inclusion criteria represent the minimum recommendations for CRT implantation in heart failure patients according to the ESC 2016 guidelines. In addition:

Patient has a LVEF ≤ 35%
Patient has a LVEDD ≥ 55mm
Patient has been in a stable medical condition for ≥ 1 month prior inclusion
Patient receives Optimal Medical Treatment (OMT)
Patient underwent complete revascularization in case of ischemia
Patients is able to understand and willing to provide a written informed consent
Patient is 18 years or older

Exclusion Criteria:

Patients who meet any of the following criteria will not participate in the study:

Patient suffers from ventricular arrhythmias which do not allow to acquire 3 consecutive regular beats during echocardiography (e.g. frequent VES, bigemini, …)
Patient suffers from severe MR, or otherwise more than moderate valvular disease
Patient suffers from unstable angina
Patient suffers from pulmonary hypertension, other than secondary to left heart disease
Patient has a life expectancy of less than 1 year
Patient is pregnant or breastfeeding
Patient has either no pacemaker / ICD or has a right ventricular pacing of < 40%, and any of the following:
Atrial fibrillation
PR duration > 250ms
Second or third degree atrioventricular block
Intrinsic QRS duration < 130ms
Patient has a right ventricular pacing of > 40% and any of the following
Sensed AV delay > 250ms
Paced AV delay > 280ms

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Antwerp	Antwerp	Belgium	2000
2	ZNA Middelheim	Antwerp	Belgium	2020
3	Hospital Erasme	Brussels	Belgium	1070
4	AZ Maria Middelares	Ghent	Belgium	9000
5	Ghent University Hospital	Ghent	Belgium	9000
6	UZ Leuven	Leuven	Belgium	3000
7	AZ Damiaan	Ostend	Belgium	8400
8	AZ Delta	Roeselare	Belgium	8800
9	Groupements des hôpitaux de l'institut catholique de Lille	Lille	France	59800 Lille
10	CHU Rennes - Pontchaillou Hospital	Rennes	France	35000
11	St. Vinzenz-Hospital	Köln	Germany	50733
12	Klinika Wad Wrodzonych Serca	Warsaw	Poland	04-628
13	Heart Institute Nicolae Stancioiu	Cluj-Napoca	Romania	400001