AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

NCT04225520 | Recruiting DMC FDA Device

• 1 other identifier: S64188_v4.0
• Study Type: interventional
• Target: 700
• Locations: 11 countries
• Sites: 24

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Effect on left ventricular function in both arms

  12 months follow-up

• 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

• Difference in 6 minute walk test distance in both arms

  12 months follow-up

• Difference in predictive value for volume response

  12 months follow-up

• Difference in predictive value for long-term patient outcome in both arms

  1 year, 3 years and 5 years follow-up

Study Arms (2)

Treatment recommendation based on guidelines

ACTIVE COMPARATOR

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

Treatment recommendation based on mechanical dyssynchrony

EXPERIMENTAL

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; Device: Cardiac resynchronization therapy OFF

Interventions

Cardiac resynchronization therapy ON DEVICE

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

Treatment recommendation based on guidelines; Treatment recommendation based on mechanical dyssynchrony

Cardiac resynchronization therapy OFF DEVICE

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

Treatment recommendation based on mechanical dyssynchrony

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a LVEF ≤ 35%
• Patient has a LVEDD ≥ 2.7cm/m² or LVEDD ≥ 50mm (m) and ≥45mm (f)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (24)

University Hospital Antwerp

Antwerp, 2000, Belgium

RECRUITING

ZNA Middelheim

Antwerp, 2020, Belgium

RECRUITING

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

RECRUITING

AZ Maria Middelares

Ghent, 9000, Belgium

RECRUITING

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

AZ Damiaan

Ostend, 8400, Belgium

RECRUITING

AZ Delta

Roeselare, 8800, Belgium

RECRUITING

Dante Pazzanese Institute of Cardiology

São Paulo, 04012-909, Brazil

RECRUITING

CHRU Brest

Brest, 29200, France

RECRUITING

Groupements des hôpitaux de l'institut catholique de Lille

Lille, 59800 Lille, France

RECRUITING

CHU Rennes - Pontchaillou Hospital

Rennes, 35000, France

RECRUITING

St. Vinzenz-Hospital

Cologne, 50733, Germany

RECRUITING

Universitätsmedizin Rostock

Rostock, 18057, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

RECRUITING

Semmelweis University Heart Center

Budapest, 1122, Hungary

RECRUITING

Paul Stradins Clinical University hospital

Riga, LV-1002, Latvia

RECRUITING

Poznan University of Medical Sciences

Poznan, 61-701, Poland

RECRUITING

Klinika Wad Wrodzonych Serca

Warsaw, 04-628, Poland

RECRUITING

Silesian Center for Heart Diseases

Zabrze, 41-800, Poland

RECRUITING

CHU de São João

Porto, 4200-319, Portugal

RECRUITING

Heart Institute Nicolae Stancioiu

Cluj-Napoca, 400001, Romania

RECRUITING

Hospital Clínico de Barcelona

Barcelona, 08036, Spain

RECRUITING

Universitätsspital Zürich

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Heart Failure; Cardiomyopathy, Dilated; Ventricular Remodeling

Interventions

Cardiac Resynchronization Therapy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cardiac Pacing, Artificial; Electric Stimulation Therapy; Therapeutics

Study Officials

• Jens-Uwe Voigt, MD, PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jens-Uwe Voigt, MD, PhD

CONTACT

+32 16 34 90 16; jens-uwe.voigt@uzleuven.be

Alexis Puvrez, MD

CONTACT

+32 16 34 58 43; alexis.puvrez@kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 13, 2020
• Study Start: December 10, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (8); FR (3); PT (1); CH (1); PL (3); LA (1); BR (1); ES (1); RO (1); HU (1); DE (3)