AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT (AMEND-CRT)
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| ClinicalTrials.gov Identifier: NCT04225520 |
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Recruitment Status :
Recruiting
First Posted : January 13, 2020
Last Update Posted : December 6, 2023
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Sponsor:
Universitaire Ziekenhuizen KU Leuven
Information provided by (Responsible Party):
Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen KU Leuven
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Left Ventricular Dyssynchrony Heart Failure Cardiomyopathy, Dilated Cardiac Remodeling, Ventricular | Device: Cardiac resynchronization therapy ON Device: Cardiac resynchronization therapy OFF | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 700 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy |
| Actual Study Start Date : | December 10, 2020 |
| Estimated Primary Completion Date : | December 1, 2025 |
| Estimated Study Completion Date : | December 1, 2030 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Treatment recommendation based on guidelines
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.
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Device: Cardiac resynchronization therapy ON
Implantation of a CRT device. Bi-ventricular pacing will be turned ON. |
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Experimental: Treatment recommendation based on mechanical dyssynchrony
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.
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Device: Cardiac resynchronization therapy ON
Implantation of a CRT device. Bi-ventricular pacing will be turned ON. Device: Cardiac resynchronization therapy OFF Implantation of a CRT device. Bi-ventricular pacing will be turned OFF. |
Primary Outcome Measures :
- Volume response and Packer Clinical Composite Score [ Time Frame: 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 :
- Effect on left ventricular function in both arms [ Time Frame: 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 quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms [ Time Frame: 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 [ Time Frame: 12 months follow-up ]≥ 45 meters difference in change from baseline to month 12
- Difference in predictive value for volume response [ Time Frame: 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 predictive value for long-term patient outcome in both arms [ Time Frame: 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 long-term patient outcome in both arms [ Time Frame: 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
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04225520
Contacts
| Contact: Jens-Uwe Voigt, MD, PhD | +32 16 34 90 16 | jens-uwe.voigt@uzleuven.be | |
| Contact: Alexis Puvrez, MD | +32 16 34 58 43 | alexis.puvrez@kuleuven.be |
Locations
Show 24 study locations
Sponsors and Collaborators
Universitaire Ziekenhuizen KU Leuven
Investigators
| Principal Investigator: | Jens-Uwe Voigt, MD, PhD | Universitaire Ziekenhuizen KU Leuven |
| Responsible Party: | Jens-Uwe Voigt, MD, PhD, Principle Investigator, Universitaire Ziekenhuizen KU Leuven |
| ClinicalTrials.gov Identifier: | NCT04225520 |
| Other Study ID Numbers: |
S64188_v4.0 |
| First Posted: | January 13, 2020 Key Record Dates |
| Last Update Posted: | December 6, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Available upon reasonable request after acceptance of publications. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen KU Leuven:
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Cardiac resynchronization therapy Heart failure Mechanical dyssynchrony Echocardiography |
Apical rocking Septal flash Left ventricle |
Additional relevant MeSH terms:
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Heart Failure Cardiomyopathies Cardiomyopathy, Dilated Ventricular Remodeling Heart Diseases |
Cardiovascular Diseases Cardiomegaly Laminopathies Genetic Diseases, Inborn Pathological Conditions, Anatomical |