Clinical trial NCT03587064: Comparison of CRT-D and CRT-DX Systems (CRT-NEXT)
Official title: Non-inferiority Randomized Clinical Investigation of CRT-DX Versus CRT-D Systems
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiac Resynchronization Therapy
Keywords: CRT-D
CRT-DX
Atrial pacing
Lead sponsor: Associazione Portatori Dispositivi Impiantabili Cardiaci
Sponsor class: OTHER
First posted: 2018-07-16
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Combined endpoint of Mortality, hospitalization due to cardiac causes and lead-related complications
timeFrame: 1 year
Secondary outcomes:
measure: Rate of implant revisions
timeFrame: 1 year
measure: Rate of inappropriate therapy of the device
timeFrame: 1 year
measure: Atrial pacing percentage
timeFrame: 1 year
measure: Exercise test
timeFrame: 1 year
measure: Device detected AT
timeFrame: 1 year
measure: Incidence of appropriate Ventricular therapy
timeFrame: 1 year
measure: Incidence of events due to short-long-short sequence
timeFrame: 1 year
measure: Implant failure
timeFrame: 1 year
measure: Procedure times
timeFrame: 1 year
measure: Atrial sensing amplitude measured by device
timeFrame: 1 year
measure: Far field oversensing incidence
timeFrame: 1 year
Other outcomes:
Locations:
city: Rho
country: Italy
facility: ASST Rhodense
state: Milano
city: Camposampiero
country: Italy
facility: Ospedale di Camposampiero
state: Padova
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti Ancona
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi
city: Campobasso
country: Italy
facility: Fondazione Giovanni Paolo II
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele - Presidio Ferrarotto
city: Catanzaro
country: Italy
facility: Clinica Sant'Anna
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese Ciaccio
city: Ferrara
country: Italy
facility: Arcispedale Sant'Anna
city: Firenze
country: Italy
facility: Ospedale Santa Maria Nuova
city: Gorizia
country: Italy
facility: Ospedale di Gorizia
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi
city: Legnago
country: Italy
facility: Ospedale Mater Salutis di Legnago
city: Mantova
country: Italy
facility: Ospedale Carlo Poma
city: Messina
country: Italy
facility: IRCSS - Centro Neurolesi Bonino Pulejo
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Napoli
country: Italy
facility: AOU Vanvitelli - Monaldi
city: Napoli
country: Italy
facility: AO dei Colli - PO Monaldi
city: Napoli
country: Italy
facility: Ospedale Federico II
city: Parma
country: Italy
facility: Azienda Ospedaliero - Universitaria di Parma
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio
city: Ragusa
country: Italy
facility: Ospedale Giovanni Paolo II
city: Torino
country: Italy
facility: Ospedale Molinette
city: Trieste
country: Italy
facility: Ospedali Riuniti Trieste
Study officials:
References: