AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

Sponsor
Universitaire Ziekenhuizen Leuven (Other)
Overall Status
Recruiting
CT.gov ID
NCT04225520
Collaborator
(none)
700
Enrollment
13
Locations
2
Arms
71.7
Anticipated Duration (Months)
53.8
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
  • Device: Cardiac resynchronization therapy ON
  • Device: Cardiac resynchronization therapy OFF
N/A

Study Design

Study Type:
Interventional
Anticipated 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 :
Dec 10, 2020
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2026

Arms and Interventions

ArmIntervention/Treatment
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.

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

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.

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.

Outcome Measures

Primary Outcome Measures

  1. Volume response and Packer Clinical Composite Score [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 continuously measured left ventricular end-systolic volume per arm and the percentage 'worsened' according to the Packer Clinical Composite Score per arm after 12 months follow-up

Secondary Outcome Measures

  1. Effect on left ventricular function in both arms [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

  2. 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]

    ≥ 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

  3. Difference in 6 minute walk test distance in both arms [12 months follow-up]

    ≥ 45 meters difference in change from baseline to month 12

  4. Difference in predictive value for volume response [12 months follow-up]

    ≥15% relative reduction in left ventricular end-systolic volume from baseline to month 12 will be considered as a response

  5. Difference in predictive value for long-term patient outcome in both arms [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

  6. Difference in long-term patient outcome in both arms [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

The proposed inclusion criteria represent the minimum recommendations for CRT implantation in heart failure patients according to the ESC 2016 guidelines. In addition:

  1. Patient has a LVEF ≤ 35%

  2. Patient has a LVEDD ≥ 55mm

  3. Patient has been in a stable medical condition for ≥ 1 month prior inclusion

  4. Patient receives Optimal Medical Treatment (OMT)

  5. Patient underwent complete revascularization in case of ischemia

  6. Patients is able to understand and willing to provide a written informed consent

  7. Patient is 18 years or older

Exclusion Criteria:
Patients who meet any of the following criteria will not participate in the study:
  1. Patient suffers from ventricular arrhythmias which do not allow to acquire 3 consecutive regular beats during echocardiography (e.g. frequent VES, bigemini, …)

  2. Patient suffers from severe MR, or otherwise more than moderate valvular disease

  3. Patient suffers from unstable angina

  4. Patient suffers from pulmonary hypertension, other than secondary to left heart disease

  5. Patient has a life expectancy of less than 1 year

  6. Patient is pregnant or breastfeeding

  7. Patient has either no pacemaker / ICD or has a right ventricular pacing of < 40%, and any of the following:

  8. Atrial fibrillation

  9. PR duration > 250ms

  10. Second or third degree atrioventricular block

  11. Intrinsic QRS duration < 130ms

  12. Patient has a right ventricular pacing of > 40% and any of the following

  13. Sensed AV delay > 250ms

  14. Paced AV delay > 280ms

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University Hospital AntwerpAntwerpBelgium2000
2ZNA MiddelheimAntwerpBelgium2020
3Hospital ErasmeBrusselsBelgium1070
4AZ Maria MiddelaresGhentBelgium9000
5Ghent University HospitalGhentBelgium9000
6UZ LeuvenLeuvenBelgium3000
7AZ DamiaanOstendBelgium8400
8AZ DeltaRoeselareBelgium8800
9Groupements des hôpitaux de l'institut catholique de LilleLilleFrance59800 Lille
10CHU Rennes - Pontchaillou HospitalRennesFrance35000
11St. Vinzenz-HospitalKölnGermany50733
12Klinika Wad Wrodzonych SercaWarsawPoland04-628
13Heart Institute Nicolae StancioiuCluj-NapocaRomania400001

Sponsors and Collaborators

  • Universitaire Ziekenhuizen Leuven

Investigators

  • Principal Investigator: Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen Leuven

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jens-Uwe Voigt, MD, PhD, Principle Investigator, Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier:
NCT04225520
Other Study ID Numbers:
  • S64188_v3.0
First Posted:
Jan 13, 2020
Last Update Posted:
Oct 6, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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, Principle Investigator, Universitaire Ziekenhuizen Leuven
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 6, 2021