Post-market Prospective, Multicenter, Randomized and Single-blinded Clinical Investigation to Evaluate Whether Cardiac Re-Synchronization Therapy (CRT) Using Automatic Continuous Atrioventricular (AV) Delay Optimization is Superior to CRT With Conventional Biventricular Stimulation (BiV). (CRUSTY +)

Post-market Prospective, Multicenter, Randomized and Single-blinded Clinical Investigation to Evaluate Whether Cardiac Re-Synchronization Therapy (CRT) Using Automatic Continuous Atrioventricular (AV) Delay Optimization is Superior to CRT With Conventional Biventricular Stimulation (BiV). (CRUSTY + Trial)

The goal of this randomized, multicenter prospective study is to demonstrate that the activation of biventricular pacing with fusion and AV optimization feature will increase the rate of CRT responders in terms of LV reverse remodeling, compared with conventional biventricular pacing.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: SyncAV function on

Detailed Description

Treatment of HFrEF with CRT. CRT is an established guideline-recommended treatment for patients who are refractory to optimized pharmacologic therapy, and have reduced ejection fraction and increased QRS duration. It works by restoring atrioventricular, inter- and intra-ventricular synchrony and in so doing, it has been shown to improve symptoms, LV systolic function and survival. Nevertheless, a significant proportion of patients (30-45%) do not benefit after CRT and are considered non-respondent. Non-response to CRT is multifactorial (poor substrate to resynchronize, difficulty in the implant, age, gender, aetiology, and/or comorbidities). Recently, other negative determinants have been identified as cause of non-responding to CRT such as the lack of fusion of ventricular contraction with the intrinsic right ventricular conduction and non-optimal AV delay programming which, in turn, is related to the duration of PR interval. Another possible reason for non-responding to CRT is a non-optimal LV pacing site.

The CRUSTY PLUS trial is aimed to establish the relevance for the success of CRT of these three factors: lack of fusion, non-optimized A-V conduction, and LV pacing site by comparing the response to CRT with a standard BIV device with fixed out-of-the-box A-V delay with that to a BIV device (Sync A-V plus) endowed with an algorithm which is continuously measuring the patients' A-V conduction and is able to adjust the stimulation parameters according to the measured PR interval, achieving a more dynamic A-V interval and allowing a perfect fusion of ventricular contraction. The algorithm is also able to optimize LV intraventricular synchrony. Sync A-V plus is endowed with a quadripolar multipoint pacing (MPP) CRT-D system allowing pacing of the LV with 2 vectors. This methodology allows a simultaneous earlier and wider excitation of ventricular tissue resulting in better synchronization and better cardiac output.

• Study Type: Interventional
• Enrollment (Estimated): 722
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio Rapacciuolo, Prof; Phone Number: 0817462235; Email: antonio.rapacciuolo@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• More than 18 years of age;
• Have signed the Informed Consent form.
• have been implanted with an Abbott CRT-D with the Sync-AV dynamic function under the current Class I or Class IIa ESC indications (2021 guidelines) for CRT implantation (including upgrades from single or dual chamber pacemakers or ICDs);
• Have to be in sinus rhythm at the Baseline visit and with Left Branch Block (LBBB) (2021 ESC/REVERSE):
• LVEF needs to be <35% while under optimal medical treatment
• to be willing to meet all study requirements and have the ability to do participate to this study.

Exclusion Criteria:

Inclusion / Exclusion criteria: Inclusion criteria: To participate in this clinical study, patients must meet ALL of the following inclusion criteria:

• More than 18 years of age;
• Have signed the Informed Consent form.
• And have been implanted with an Abbott CRT-D with the Sync-AV dynamic function under the current Class I or Class IIa ESC indications (2021 guidelines) for CRT implantation (including upgrades from single or dual chamber pacemakers or ICDs);
• Have to be in sinus rhythm at the Baseline visit and with Left Branch Block (LBBB) (2021 ESC/REVERSE):
• LVEF needs to be <35% while under optimal medical treatment
• In addition, patients need to be willing to meet all study requirements and have the ability to do participate to this study.

Exclusion criteria: Patients who meet any of the following exclusion criteria are NOT eligible to participate in the clinical study:

• Having suffered a myocardial infarction or unstable angina in the 40 days prior to inclusion.
• Having undergone coronary revascularization (PTCA, Stent or CABG) in the 4 weeks prior to inclusion.
• Having suffered a Cerebrovascular Accident (CVA) or a Transient Ischemic Accident (TIA) in the 3 months prior to inclusion.
• NYHA Class IV.
• Having received a heart transplant or being waiting to receive it (status I classification);
• Suffering from primary valve disease requiring surgical intervention.
• Having long-lasting or permanent atrial fibrillation
• Showing inadequate transthoracic echocardiographic images which will not allow to establish cardiac output and LV volumes.
• Having a life expectancy <12months.
• Being pregnant or planning to become pregnant during the clinical investigation.
• Inability to meet the monitoring schedule.
• Currently participating in any other clinical interventional research.
• Having a permanent high degree AV block

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SyncAV plus group; Patients implanted with a CRT-D programmed with SyncAV plus function ON.	Device: SyncAV function on; CRT-D with SyncAV plus activated
No Intervention: Biv Trad; Patients implanted with a CRT-D programmed with fixed AV delay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in left ventricular end systolic volume (LVESV) between baseline and 6 months	The primary endpoint is response to CRT defined as > 15% relative reduction in Left Ventricular End Systolic Volume (LVESV) at 6 months after implantation, evaluated by Echocardiography	Month 6
Reduction in QRS duration after randomization	The primary endpoint is the reduction of QRS duration compared to the intrinsic QRS. Defined as > 13% relative reduction in QRS duration compared with the intrinsic QRS, evaluated by ECG.Defined as > 13% relative reduction in QRS duration compared with the intrinsic QRS, evaluated by ECG.	within 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of CRT Responders at 12 months after MPP activation programmed after the 6 Months follow-up.	Percentage of non-responders at 6 Months responders at 12 Months with MPP	Month 6

Collaborators and Investigators

• Sponsor: Antonio Rapacciuolo
• Investigators: Study Chair: Jaume Francisco Pascual, Dr, Hospital Vall d'Hebron; Study Chair: Nuria Rivas Gandara, Dr, Hospital Vall d'Hebron; Study Chair: Angelo Auricchio, Prof, Istituto Cardiocentro Ticino

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: DE-66-22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No