MOre REsponse on Cardiac Resynchronization Therapy With MultiPoint Pacing

This study is designed as a prospective, randomized, multi-center trial. Data will be collected at enrollment, baseline, implant procedure, patient classification, 6 months and 12 months of follow-up. During the 6-month visit, the patient's response to CRT will be evaluated according to LVESV reduction. Patients with an LVESV reduction of at least 15% will be classified as responders. These patients will terminate their participation in the study and return to the center's standard practice. Patients with an LVESV reduction less than 15% will be classified as non-responders and the MPP feature will be activated according to randomization result and they will be followed until the 12-month visit.

• MPP (Device): All patients enrolled in the study will be implanted (according to current Guidelines) with an MPP compatible CRT device. The MPP feature will be evaluated in two study phases. Patients randomized to MPP in Phase I will have MPP programmed per the physician's discretion ("no mandated MPP programming") and patients randomized to MPP in Phase II will have MPP programmed per protocol requirements ("mandated MPP programming").

Primary outcomes

• Percentage of Non-responder Patients Who Converted to Responders [Non-responder to responder conversion rate between randomization at 6 months and 12 months]: The primary endpoint of this study is evaluated at 12 months after enrollment and it is defined as the percentage of non-responder patients converted to responders after 6 months of MPP feature turned ON compared to baseline, as measured by Left Ventricular End Systolic Volume (LVESV) reduction of at least 15%.

Secondary outcomes

• Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase [Baseline vs 6 Months]: Reduction of LVESV between baseline and 6 Months visit
• Clinical Composite Score Evaluation [Baseline vs 12 Months]: Packer's Clinical Composite Score evaluation between baseline and 12 months as defined below, * Worsened: the patient died because of cardiovascular reasons OR experienced a HF event OR demonstrated worsening in NYHA functional class, or had worsening of patient global assessment (PGA) score compared with the last observation * Improved: the patient survived without an HF event AND demonstrated either improvement in NYHA functional class or improvement in PGA score or both compared with the last observation * Unchanged: the patient was neither improved nor worsened
• Reverse Left Ventricular (LV) Remodeling [Baseline vs 12 Months]: Evaluation of Reverse LV remodeling, measured as changed in left ventricular end-systolic volume (LVESV) from baseline to 12 months
• NYHA Class Changes [Baseline vs 12 Months]: Evaluation of NYHA Class changes between baseline and 12 months. Increasing functional class is associated with greater risk of death or hospitalization.
• 6MWT Changes [Baseline vs 12 Months]: Evaluation of the patient's activity status using 6 Minutes Walking Test changes from baseline to 12 months FU
• Patient's QoL Score Changes (MLWHF) [Baseline vs 12 Months]: Evaluation of patient's Quality of Life score using Minnesota Living with Heart Failure (MLWHF) Questionnaires. The MLWHF Questionnaire consists of 21 questions with a range in overall scores of 0 to 105 points (lower scores indicate better quality of life).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Meets the current ESC Guidelines or ACCF/AHA/HRS Class I or Class IIa indications for CRT implant (including upgrades from single or dual chamber ICDs)
* Must be willing and able to comply with study requirements
* Must indicate their understanding of the study and willingness to participate by signing an appropriate informed consent form

Exclusion Criteria:

* Already had a CRT device implanted
* Myocardial Infarction, unstable angina within 40 days prior the enrollment
* Recent cardiac revascularization (PTCA, Stent or CABG) in the 4 weeks prior to enrollment or planned for the 3 months following
* Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA) in the 3 months prior the enrollment
* Primary valvular disease
* Atrial Fibrillation:

  * Persistent AF at the time of enrollment
  * Permanent AF not treated with AV node ablation within 2 weeks from the CRT implant
  * History or incidence of Paroxysmal or Persistent AF within 30 days prior the enrollment
* Unable to comply with the follow up schedule
* Less than 18 years of age
* Pregnant or are planning to become pregnant during the duration of the investigation
* Classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 12 months
* Undergone a cardiac transplantation
* Life expectancy < 12 months
* Currently participating in any other clinical investigation

Participant flow

Outcome results

• Percentage of Non-responder Patients Who Converted to Responders (Primary), Count of participants, Participants: MPP ON 84; BiVP 170
• Reduction of Left Ventricular End-systolic Volume (LVESV) in Acute Phase (Secondary), Mean, percentage of LVESV change: MPP ON 2.1 +/- 11.2; BiVP 0.1 +/- 3.3
• Clinical Composite Score Evaluation (Secondary), Count of participants, Participants: MPP ON 161; BiVP 312
• Reverse Left Ventricular (LV) Remodeling (Secondary), Mean, mL: MPP ON 3.0 +/- 24; BiVP 3.8 +/- 23.1
• NYHA Class Changes (Secondary), Count of participants, Participants: MPP ON 125; BiVP 287
• 6MWT Changes (Secondary), Mean, meters: MPP ON 41.1 +/- 113.6; BiVP 46 +/- 121.1
• Patient's QoL Score Changes (MLWHF) (Secondary), Mean, score on a scale: MPP ON -11.6 +/- 20.0; BiVP -12.2 +/- 21.7

Adverse events

Time frame: 6 months to 12 months after randomization

Serious adverse events by term

56 more terms not shown.

Other adverse events by term

106 more sites not listed.

• Results publication: Leclercq C, Burri H, Curnis A, Delnoy PP, Rinaldi CA, Sperzel J, Lee K, Calo L, Vicentini A, Concha JF, Thibault B. Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I. Eur Heart J. 2019 Sep 14;40(35):2979-2987. doi: 10.1093/eurheartj/ehz109. PMID 30859220
• Results publication: Leclercq C, Burri H, Curnis A, Delnoy PP, Rinaldi CA, Sperzel J, Lee K, Cohorn C, Thibault B; MORE-CRT MPP Investigators. Rationale and design of a randomized clinical trial to assess the safety and efficacy of multipoint pacing therapy: MOre REsponse on Cardiac Resynchronization Therapy with MultiPoint Pacing (MORE-CRT MPP-PHASE II). Am Heart J. 2019 Mar;209:1-8. doi: 10.1016/j.ahj.2018.12.004. Epub 2018 Dec 8. PMID 30616009

• Study Protocol and Statistical Analysis Plan (PDF, 2018-04-09)

• Christophe Leclercq, Study chair, Centre Cardio-Pneumologique, CHU Pontchaillou