Left Ventricular DyssynchronyAMEND-CRTNCT04225520
AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT
A study testing Cardiac resynchronization therapy ON and Cardiac resynchronization therapy OFF in people with Left Ventricular Dyssynchrony and Heart Failure, run by Universitaire Ziekenhuizen KU Leuven at 24 sites in 11 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Left Ventricular Dyssynchrony, Heart Failure, Cardiomyopathy, Dilated
- What is being tested?
- Cardiac resynchronization therapy ON and Cardiac resynchronization therapy OFF
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 24 sitesin 11 countries
- Study dates
- 10 Dec 2020to 1 Dec 2030
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
(- - - - - - - - - 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
Trial locations and contacts
24 sites in 11 countries.
24 sites in 11 countries
Belgium8 sites
University Hospital Antwerp
Antwerp, 2000
ZNA Middelheim
Antwerp, 2020
AZ Sint-Jan Brugge
Bruges, 8000
AZ Maria Middelares
Ghent, 9000
Ghent University Hospital
Ghent, 9000
UZ Leuven
Leuven, 3000
AZ Damiaan
Ostend, 8400
AZ Delta
Roeselare, 8800
France3 sites
CHRU Brest
Brest, 29200
Groupements des hôpitaux de l'institut catholique de Lille
Lille, 59800 Lille
CHU Rennes - Pontchaillou Hospital
Rennes, 35000
Germany3 sites
St. Vinzenz-Hospital
Cologne, 50733
Universitätsmedizin Rostock
Rostock, 18057
Universitätsklinikum Würzburg
Würzburg, 97080
Poland3 sites
Poznan University of Medical Sciences
Poznan, 61-701
Klinika Wad Wrodzonych Serca
Warsaw, 04-628
Silesian Center for Heart Diseases
Zabrze, 41-800
About this study
Official title: Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy
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
- Being tested
- Cardiac resynchronization therapy ON, Cardiac resynchronization therapy OFF
- Keywords
- Cardiac resynchronization therapy, Heart failure, Mechanical dyssynchrony, Echocardiography, Apical rocking, Septal flash, Left ventricle
- Medical subject headings
- Heart Failure, Cardiomyopathy, Dilated, Ventricular Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac resynchronization therapy ONDevice
Implantation of a CRT device. Bi-ventricular pacing will be turned ON.
Cardiac resynchronization therapy OFFDevice
Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Cardiac resynchronization therapy ON; Device: Cardiac resynchronization therapy OFF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months follow-up
Secondary outcomes (6)
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
Measured: 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
- ≥ 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
Measured: 12 months follow-up
Difference in 6 minute walk test distance in both arms
≥ 45 meters difference in change from baseline to month 12
Measured: 12 months follow-up
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
Measured: 12 months follow-up
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
Measured: 1 year, 3 years and 5 years follow-up
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
Measured: 3 years and 5 years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start10 Dec 2020
- Primary completion31 Dec 2027 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Left Ventricular DyssynchronyStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen KU Leuven
- Investigators
- Jens-Uwe Voigt, MD, PhD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225520
- Sponsor's protocol ID
- S64188_v5.0
- Acronym
- AMEND-CRT
- Status last verified
- Apr 2026
- First submitted
- 8 Jan 2020
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: Available upon reasonable request after acceptance of publications.