Comparison of CRT-D and CRT-DX Systems (CRT-NEXT)

Heart Failure Clinical Trial

— CRT-NEXT  

Official title:

Non-inferiority Randomized Clinical Investigation of CRT-DX Versus CRT-D Systems

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03587064
• Other study ID #: APDIC
• Status: Recruiting
• Phase: N/A
• Start date: October 22, 2018
• Est. completion date: April 2025

Study information

• Verified date: November 2023
• Source: Associazione Portatori Dispositivi Impiantabili Cardiaci
• Contact: Mauro Biffi, MD
• Phone: 0516363434
• Email: mbiffi64[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The principal objective is to test non-inferiority of the CRT-DX system as compared to a conventional CRT-D system, in terms of the combined endpoint of mortality, hospitalizations due cardiovascular causes, any complication leading to loss of lead functionality, in the subset of patients without evidence of sinus dysfunction on optimal therapy.

Description:

Resting heart rate is strongly associated with incident worsening Heart Failure (HF) and mortality. Current devices for cardiac resynchronization (CRT-D) normally provide atrio-ventricular (AV) sequential pacing modes during resynchronization, but the best pacing programming strategy is not clear.

On the one hand a basic rate of 50 to 70 bpm (optionally with some rate-responsive function) could be considered for therapy up-titration, specifically betablockers; on the other hand, increasing pacing rates may partially reduce benefits from resynchronization, reducing filling time and contractility reservoir.

The Pegasus investigation is the only large randomized investigation comparing DDD with 70 bpm basic rate to DDD(R) @40 bpm. Results showed no difference in investigation endpoints, including mortality and HF-hospitalization.

These results may support the use of a device implementing both a CRT function and a right ventricular single-lead with and an atrial sensing dipole (CRT-DX system). This system can track ventricular pacing and resynchronization following atrial sensing, even if it cannot provide atrial pacing support. It should be assessed whether such limitation is counterbalanced by the advantages related to the reduced number of necessary leads, with simplified implantation and less complications.

The objective of the investigation is to assess whether atrial pacing support is really necessary in the subset of patients with indication to CRT-D and no evidence of sinus dysfunction on optimal therapy. The investigation will test the hypothesis that a CRT-DX system is not inferior to a conventional CRT-D system in this class of subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 640
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male and female patients = 18 years old

2. Patients willing to participate in the investigation and signing the Patient Informed Consent (PIC) Form;

3. Indication to CRT-D implant according to current ESC Guidelines on cardiac pacing and cardiac resynchronization therapy

4. Sinus rhythm at time of implant;

5. Optimized medical therapy according to current ESC Guidelines

6. Rest heart rate (HR) >45 bpm at baseline ECG, with betablocker therapy at optimal medical dosage; or, if rest HR<45 bpm: maximum heart rate at the 6- minute walking test >85 bpm.

Exclusion Criteria:

1. Any indication to atrial pacing according to current guidelines;

2. Both: resting heart rate <45 bpm at baseline ECG, with betablocker therapy at optimal medical dosage and maximum heart rate at the 6-minute walking test <85 bpm;

3. NYHA Class IV;

4. Permanent Atrial Fibrillation

5. Replacement of/upgrading from previously implanted pacing system;

6. Dialysis patients;

7. Pregnant or breast-feeding women.

Related Conditions & MeSH terms

• Cardiac Resynchronization Therapy
• Heart Failure

Intervention

Device:
• Conventional 3-lead CRT defibrillator system implantation
Conventional 3-lead(1 atrial and 2 ventricular leads) system implantation
• 2-lead CRT defibrillator system implantation
2-lead (2 ventricular leads with dipole for atrial sensing) DX system implantation

Locations

Country	Name	City	State
Italy	AOU Ospedali Riuniti Ancona	Ancona
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi	Bologna
Italy	Fondazione Giovanni Paolo II	Campobasso
Italy	Ospedale di Camposampiero	Camposampiero	Padova
Italy	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele - Presidio Ferrarotto	Catania
Italy	Azienda Ospedaliera Pugliese Ciaccio	Catanzaro
Italy	Clinica Sant'Anna	Catanzaro
Italy	Arcispedale Sant'Anna	Ferrara
Italy	Ospedale Santa Maria Nuova	Firenze
Italy	Ospedale di Gorizia	Gorizia
Italy	Ospedale Vito Fazzi	Lecce
Italy	Ospedale Mater Salutis di Legnago	Legnago
Italy	Ospedale Carlo Poma	Mantova
Italy	IRCSS - Centro Neurolesi Bonino Pulejo	Messina
Italy	Ospedale San Gerardo	Monza
Italy	AO dei Colli - PO Monaldi	Napoli
Italy	AOU Vanvitelli - Monaldi	Napoli
Italy	Ospedale Federico II	Napoli
Italy	Azienda Ospedaliero - Universitaria di Parma	Parma
Italy	Fondazione Toscana Gabriele Monasterio	Pisa
Italy	Ospedale Giovanni Paolo II	Ragusa
Italy	ASST Rhodense	Rho	Milano
Italy	Ospedale Molinette	Torino
Italy	Ospedali Riuniti Trieste	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
Associazione Portatori Dispositivi Impiantabili Cardiaci

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined endpoint of Mortality, hospitalization due to cardiac causes and lead-related complications	It includes number of patients who experienced death, hospitalization due to cardiac causes, or any lead-related complication leading to loss of functionality (including lead dislodgement, conduction or insulation failure, loss of sensing or capture that couldn't resolved by reprogramming)	1 year
Secondary	Rate of implant revisions	Rate of implant revisions to add, replace, reposition, and remove an atrial pacing lead.	1 year
Secondary	Rate of inappropriate therapy of the device	Inappropriate detections and interventions of high rate ventricular episodes.	1 year
Secondary	Atrial pacing percentage	In the conventional CRT-D group, atrial pacing percentage.	1 year
Secondary	Exercise test	Six minute walking test distance at one year	1 year
Secondary	Device detected AT	Incidence of atrial tachyarrhythmias (AT)	1 year
Secondary	Incidence of appropriate Ventricular therapy	Incidence of Ventricular Arrhythmias (VA) requiring therapy delivery	1 year
Secondary	Incidence of events due to short-long-short sequence	Incidence of both VA and AT due to bradycardia or short-long-short sequence	1 year
Secondary	Implant failure	Impossibility to implant any component (leads and device) of the initially planned system	1 year
Secondary	Procedure times	Skin-to-skin and fluoroscopy time	1 year
Secondary	Atrial sensing amplitude measured by device	Atrial sensing amplitude measured by devices in both investigation arms	1 year
Secondary	Far field oversensing incidence	Incidence of far field oversensing episodes in both investigation arms	1 year