AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

Not Applicable

Recruiting

• Conditions: Left Ventricular Dyssynchrony; Heart Failure; Cardiomyopathy, Dilated; Cardiac Remodeling, Ventricular
• Interventions: Device: Cardiac resynchronization therapy ON; Device: Cardiac resynchronization therapy OFF

• Registration Number: NCT04225520
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-08
• Study First Submitted QC: 2020-01-08
• Study First Posted: 2020-01-13
• Study Start: 2020-12-10
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-29
• Last Update Posted: 2023-12-06
• Primary Completion: 2025-12-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment recommendation based on guidelines	Cardiac resynchronization therapy ON	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.
Treatment recommendation based on mechanical dyssynchrony	Cardiac resynchronization therapy ON	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.
Treatment recommendation based on mechanical dyssynchrony	Cardiac resynchronization therapy OFF	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.

Primary Outcome Measures

Name	Time	Method
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 left ventricular end-systolic volume and the proportion of patients 'worsened' according to the Packer Clinical Composite Score after 12 months follow-up.

Secondary Outcome Measures

Name	Time	Method
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 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
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 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 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

Trial Locations

Locations (24)

AZ Maria Middelares; 🇧🇪 Ghent, Belgium

ZNA Middelheim; 🇧🇪 Antwerp, Belgium

AZ Damiaan; 🇧🇪 Ostend, Belgium

University Hospital Antwerp; 🇧🇪 Antwerp, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

AZ Sint-Jan Brugge; 🇧🇪 Brugge, Belgium

Ghent University Hospital; 🇧🇪 Ghent, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

Groupements des hôpitaux de l'institut catholique de Lille; 🇫🇷 Lille, France

Dante Pazzanese Institute of Cardiology; 🇧🇷 São Paulo, Brazil

CHU Rennes - Pontchaillou Hospital; 🇫🇷 Rennes, France

CHRU Brest; 🇫🇷 Brest, France

Universitätsmedizin Rostock; 🇩🇪 Rostock, Germany

St. Vinzenz-Hospital; 🇩🇪 Köln, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany

Semmelweis University Heart Center; 🇭🇺 Budapest, Hungary

Klinika Wad Wrodzonych Serca; 🇵🇱 Warsaw, Poland

Poznan University of Medical Sciences; 🇵🇱 Poznań, Poland

Paul Stradins Clinical University hospital; 🇱🇻 Riga, Latvia

Silesian Center for Heart Diseases; 🇵🇱 Zabrze, Poland

Universitätsspital Zürich; 🇨🇭 Zürich, Switzerland

Hospital Clínico de Barcelona; 🇪🇸 Barcelona, Spain

CHU de São João; 🇵🇹 Porto, Portugal

Heart Institute Nicolae Stancioiu; 🇷🇴 Cluj-Napoca, Romania