AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

Heart Failure Clinical Trial

— AMEND-CRT  

Official title:

Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04225520
• Other study ID #: S64188_v4.0
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2020
• Est. completion date: December 1, 2030

Study information

• Verified date: November 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Jens-Uwe Voigt, MD, PhD
• Phone: +32 16 34 90 16
• Email: jens-uwe.voigt[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: December 1, 2030
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

(- - - - - - - - - Inclusion Criteria - - - - - - - - -)

The proposed inclusion criteria represent the minimum recommendations for CRT implantation in heart failure patients according to the ESC 2021 guidelines. In addition:

• Patient has a LVEF = 35%

• Patient has a LVEDD = 2.7cm/m² or LVEDD = 50mm (m) and =45mm (f)

• Patient has been in a stable medical condition for = 1 month prior inclusion

• 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 with the following conditions will be excluded:

• unreliable left ventricular volume measurements

• severe MR or more than moderate other valvular disease

• pulmonary hypertension, other than secondary to left heart disease

• patient on hemodialysis

• life expectancy < 1 year

• pregnant or breastfeeding

Patients with prior right ventricular pacing between 20% to 80% will be excluded.

Patients with prior right ventricular pacing = 20% or no pacemaker / ICD will be excluded if they have any of the following criteria:

• PR duration > 250ms

• second / third degree atrioventricular block

• intrinsic QRS duration < 130ms

• atrial fibrillation with resting HR < 50/min or > 80/min

Patients with prior right ventricular pacing = 80% will be excluded if they have any of the following criteria:

• sensed AV delay > 250ms

• paced AV delay > 280ms

Patients with a prior pacemaker / ICD scheduled for LBBaP will be excluded regardless of pacing percentage

Related Conditions & MeSH terms

• Cardiac Remodeling, Ventricular
• Cardiomyopathies
• Cardiomyopathy, Dilated
• Heart Failure
• Left Ventricular Dyssynchrony
• Ventricular Remodeling

Intervention

Device:
• Cardiac resynchronization therapy ON
Implantation of a CRT device. Bi-ventricular pacing will be turned ON.
• Cardiac resynchronization therapy OFF
Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	ZNA Middelheim	Antwerp
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	AZ Maria Middelares	Ghent
Belgium	Ghent University Hospital	Ghent
Belgium	UZ Leuven	Leuven
Belgium	AZ Damiaan	Ostend
Belgium	AZ Delta	Roeselare
Brazil	Dante Pazzanese Institute of Cardiology	São Paulo
France	CHRU Brest	Brest
France	Groupements des hôpitaux de l'institut catholique de Lille	Lille
France	CHU Rennes - Pontchaillou Hospital	Rennes
Germany	St. Vinzenz-Hospital	Köln
Germany	Universitätsmedizin Rostock	Rostock
Germany	Universitätsklinikum Würzburg	Würzburg
Hungary	Semmelweis University Heart Center	Budapest
Latvia	Paul Stradins Clinical University hospital	Riga
Poland	Poznan University of Medical Sciences	Poznan
Poland	Klinika Wad Wrodzonych Serca	Warsaw
Poland	Silesian Center for Heart Diseases	Zabrze
Portugal	CHU de São João	Porto
Romania	Heart Institute Nicolae Stancioiu	Cluj-Napoca
Spain	Hospital Clínico de Barcelona	Barcelona
Switzerland	Universitätsspital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Countries where clinical trial is conducted

Belgium,  Brazil,  France,  Germany,  Hungary,  Latvia,  Poland,  Portugal,  Romania,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume response and Packer Clinical Composite Score	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.	12 months follow-up
Secondary	Effect on left ventricular function in both arms	= 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	12 months follow-up
Secondary	Difference in quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms	= 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	12 months follow-up
Secondary	Difference in 6 minute walk test distance in both arms	= 45 meters difference in change from baseline to month 12	12 months follow-up
Secondary	Difference in predictive value for volume response	=15% relative reduction in left ventricular end-systolic volume from baseline to month 12 will be considered as a response	12 months follow-up
Secondary	Difference in predictive value for long-term patient outcome in both arms	Cox's proportional hazards model: At 1 year for 'worsened' PCCS; At 3 and 5 years for cardiovascular mortality and heart failure hospitalization	1 year, 3 years and 5 years follow-up
Secondary	Difference in long-term patient outcome in both arms	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	3 years and 5 years follow-up