Bifocal Right Ventricular PAcing in Right Bundle Branch blocK and Heart Failure With Reduced Ejection Fraction. The Study Tests the Superiority of Right Ventricular Bifocal Stimulation Over VVI Implantable Defibrillator in Right Bundle Branch Block and Heart Failure.

NCT03524001 | Terminated

• 1 other identifier: CE 194/17
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Cardiac resynchronization therapy (CRT) is known to improve cardiac performance and to reduce morbidity and mortality in reduced-ejection fraction heart failure (HFrEF) despite optimal medical therapy (OMT). Several studies have shown that patients with with left bundle branch block (LBBB) respond favourably to CRT, whereas there is less certainty about non-LBBB morphology. Specifically, whether patients with right bundle branch block (RBBB) and HFrEF benefit from CRT is unclear. Some studies suggest lack of favourable outcomes. It follows from this that VVI implantable defibrillator are implanted in most RBBB patients.On the other hand right ventricular bifocal stimulation could be useful as an alternative approach in patient with RBBB. It consists of two endocardial leads implanted in right ventricle. The first lead is implanted in His bundle area, and the second lead is in the right ventricle apex. In this way bifocal pacing could decrease the inter- and intraventricular delays, thus improving left ventricular hemodynamics. However no specifically randomized studies are designed to date. PURPOSE: To demonstrate the superiority of right ventricular bifocal stimulation over placebo (VVI implantable defibrillator) in RBBB and HFrEF despite OMT. DESIGN Multicenter prospective randomized, double blind cross-over study. MASKING Investigator responsible for device programming is masked from having knowledge about clinical, functional, and echocardiographic data. On the other hand echocardiographist is masked from having knowledge about stimulation mode. Patients are masked from having knowledge about their clinical, functional, and device data. POPULATION At least fifty patients would be enrolled. The enrollment period should be one year. Study overall duration should be two years. ELIGIBILITY CRITERIA RBBB and HFrEF (left ventricular ejection fraction ≤35%) in sinus rhythm, in NYHA class II-III or ambulatory IV despite OMT. EXCLUSION CRITERIA

• Refusal or withdrawal of informed consent.Renal failure (glomerular filtration rate ≤ 60 ml/min).Life expectancy \< 12 months.Active neoplasm.Permanent atrial fibrillation.40 days following acute coronary syndrome.Atrio-ventricular block (from second degree AV block).Valvular heart disease with surgery indications. PROTOCOL Each patient undergoes baseline assessment. Pharmacological therapy, hospitalization,NYHA functional class, QRS complex informations, type of heart disease and comorbidities are collected. Quality of life (QOL) is defined by Minnesota Living with Heart Failure questionnaire. Functional capacity is assessed by 6MWT (optionally by cardiopulmonary exercise test). Trans-thoracic echocardiogram is performed, analyzing: left-ventricle diameters and volumes, left-ventricle ejection fraction (LVEF), left atrial diameter and area, TAPSE,valvulopathy,systolic pulmonary artery pressure. All patients undergo bifocal right ventricular resynchronization therapy: right atrial lead is implanted, whereas the first ventricular lead is placed in His bundle area, and the second ventricular lead in the right ventricle apex. Then the leads are connected to the respective channels of a CRT-D generator.After the implant, all devices are programmed in VVI mode. After the first 40±10 days (first f-up) patients are 1:1 randomized to VVI mode 40 beats/minute (placebo arm) or bifocal DDD-mode 60 beats/minute (with VV delay 0 msec and optimal AV delay). After six months (second f-up) a clinical and instrumental assessment equal to baseline is performed, as well as devices electrical parameters control. Then arms cross-over is performed (from VVI-mode to bifocal DDD-mode and vice versa). At 12 months (end of follow-up) an evaluation equal to that performed at 6 months is assessed. Echocardiographic data are unravelled to the investigator responsible for device programming. In this way the stimulation mode able to determine the best clinical improved (VVI or bifocal DDD mode) is programmed and the study closes. PRIMARY ENDPOINT The main assumption is that bifocal stimulation can increase of at least 20% the distance walked during 6MWT in respect of baseline and VVI-mode.The primary endpoint is the distance walked (expressed by meters) during 6MWT, as assessed at baseline, 6-months follow-up and 12 months follow up. Specifically changes in 6MWT observed during bifocal DDD-mode compared to baseline and to VVI mode would be significative if there is an increase of at least 20%. SECONDARY ENDPOINT Secondary endpoint is bifocal stimulation therapy response, defined by at least one of the following criteria, evaluated at baseline, 6-months follow-up and 12 months-follow-up in comparison to baseline and VVI mode: NYHA functional class improvement; changes in 6MWT, defined by an increase in distance walked major or equal to 30%; LVEF improvement major or equal to 25%;Left ventricular telesystolic volume reduction major or equal to 15%

Conditions

Right Bundle-Branch Block; Heart Failure With Reduced Ejection Fraction; Bifocal Stimulation

Outcome Measures

Primary Outcomes (1)

• Change (expressed as a percentage) in distance walked during six-minute walk test (6MWT). 6MWT distance is expressed in meters

  the primary endpoint is the distance walked during 6MWT, expressed in meters. Specifically changes (expressed as a percentage) in 6MWT distance observed during bifocal DDD-mode compared to baseline and to VVI mode are registered and would be significative if there is an increase of at least 20%.

  baseline, 6 months follow-up, 12 months follow-up

Secondary Outcomes (3)

• New York Heart Association (NYHA) functional class improvement

  baseline, 6 months follow-up, 12 months follow-up

• Left ventricular ejection fraction (LVEF) improvement major or equal than 25% compared to baseline and VVI mode, as evaluated by echocardiography.

  baseline, 6 months follow-up, 12 months follow-up

• Left ventricular telesystolic volume reduction major or equal than 15% compared to baseline and VVI mode, as assessed by echocardiography.

  baseline, 6 months follow-up, 12 months follow-up

Study Arms (2)

Bifocal stimulation

ACTIVE COMPARATOR

Active comparator is represented by programming bifocal stimulation (bifocal DDD mode). Every patients will undergo crossover randomization (from bifocal DDD mode to VVI and vice versa).

Device: Compare VVi mode versus DDD bifocal stimulation through crossover randomization

VVI 40

PLACEBO COMPARATOR

Placebo comparator is represented by programming the device in VVI mode 40/mins. Every patients will undergo crossover randomization (from VVI to bifocal DDD mode and vice versa).

Device: Compare VVi mode versus DDD bifocal stimulation through crossover randomization

Interventions

Compare VVi mode versus DDD bifocal stimulation through crossover randomization DEVICE

All patients undergo bifocal right ventricular resynchronization therapy: right atrial lead is implanted, whereas first ventricular lead is placed in His bundle area, and the second ventricular lead in the right ventricle apex.Then the leads are connected to CRT-D generator.After the implant, all devices are programmed in VVI mode. After the first 40±10 days (first f-up) patients are 1:1 randomized to VVI mode 40 beats/minute (placebo arm) or bifocal DDD-mode 60 beats/minute.After six months (second follow-up) a clinical and instrumental assessment equal to baseline is performed. Then arms cross-over is performed (from VVI-mode to bifocal DDD-mode and vice versa). At 12 months (end of follow-up) an evaluation equal to that performed at 6 months is assessed. Echocardiographic data are unravelled to the investigator that plans stimulation mode able to determine the best clinical improved.

Bifocal stimulation; VVI 40

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with RBBB and HFrEF (defined by left ventricular ejection fraction ≤35%) in sinus rhythm, who remain in NYHA class II-III or ambulatory NYHA class IV despite OMT.

You may not qualify if:

• Refusal or withdrawal of informed consent.
• Renal failure (defined by an estimated glomerular filtration rate ≤ 60 ml/min)
• Life expectancy \< 12 months
• Active neoplasm
• Permanent atrial fibrillation
• days following acute coronary syndrome
• Atrio-ventricular block (from second degree AV block)
• Valvular heart disease with surgery indications

Sponsors & Collaborators

• Azienda Ospedaliero Universitaria Maggiore della Carita: lead

Study Sites (1)

Hospital "Maggiore della Carità", Division of Cardiology

Novara, 28100, Italy

Location

Related Publications (3)

• Nery PB, Ha AC, Keren A, Birnie DH. Cardiac resynchronization therapy in patients with left ventricular systolic dysfunction and right bundle branch block: a systematic review. Heart Rhythm. 2011 Jul;8(7):1083-7. doi: 10.1016/j.hrthm.2011.01.041. Epub 2011 Feb 4.

  PMID: 21300176 RESULT

• Barold SS, Audoglio R, Ravazzi PA, Diotallevi P. Is bifocal right ventricular pacing a viable form of cardiac resynchronization? Pacing Clin Electrophysiol. 2008 Jul;31(7):789-94. doi: 10.1111/j.1540-8159.2008.01093.x. No abstract available.

  PMID: 18684274 RESULT

• Res JC, Bokern MJ, de Cock CC, van Loenhout T, Bronzwaer PN, Spierenburg HA; BRIGHT Investigators. The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study. Europace. 2007 Oct;9(10):857-61. doi: 10.1093/europace/eum147. Epub 2007 Aug 7.

  PMID: 17684064 RESULT

MeSH Terms

Conditions

Bundle-Branch Block

Condition Hierarchy (Ancestors)

Heart Block; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 14, 2018
• Study Start: February 1, 2018
• Primary Completion: June 27, 2022
• Study Completion: July 10, 2022
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)