Clinical trial NCT04225520: AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT
Official title: Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Left Ventricular Dyssynchrony
Heart Failure
Cardiomyopathy, Dilated
Cardiac Remodeling, Ventricular
Keywords: Cardiac resynchronization therapy
Heart failure
Mechanical dyssynchrony
Echocardiography
Apical rocking
Septal flash
Left ventricle
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: (- - - - - - - - - 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

Primary outcomes:
measure: Volume response and Packer Clinical Composite Score
timeFrame: 12 months follow-up
Secondary outcomes:
measure: Effect on left ventricular function in both arms
timeFrame: 12 months follow-up
measure: Difference in quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms
timeFrame: 12 months follow-up
measure: Difference in 6 minute walk test distance in both arms
timeFrame: 12 months follow-up
measure: Difference in predictive value for volume response
timeFrame: 12 months follow-up
measure: Difference in predictive value for long-term patient outcome in both arms
timeFrame: 1 year, 3 years and 5 years follow-up
measure: Difference in long-term patient outcome in both arms
timeFrame: 3 years and 5 years follow-up
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Ghent
country: Belgium
facility: AZ Maria Middelares
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Ostend
country: Belgium
facility: AZ Damiaan
city: Roeselare
country: Belgium
facility: AZ Delta
city: São Paulo
country: Brazil
facility: Dante Pazzanese Institute of Cardiology
city: Brest
country: France
facility: CHRU Brest
city: Lille
country: France
facility: Groupements des hôpitaux de l'institut catholique de Lille
city: Rennes
country: France
facility: CHU Rennes - Pontchaillou Hospital
city: Köln
country: Germany
facility: St. Vinzenz-Hospital
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Budapest
country: Hungary
facility: Semmelweis University Heart Center
city: Riga
country: Latvia
facility: Paul Stradins Clinical University hospital
city: Poznań
country: Poland
facility: Poznan University of Medical Sciences
city: Warsaw
country: Poland
facility: Klinika Wad Wrodzonych Serca
city: Zabrze
country: Poland
facility: Silesian Center for Heart Diseases
city: Porto
country: Portugal
facility: CHU de São João
city: Cluj-Napoca
country: Romania
facility: Heart Institute Nicolae Stancioiu
city: Barcelona
country: Spain
facility: Hospital Clínico de Barcelona
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Jens-Uwe Voigt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: