Clinical trial NCT05815745: "Physiological vs Right Ventricular Pacing Outcome Trial Evaluated for bradyCardia Treatment" (PROTECT-HF)
Official title: Physiological vs Right Ventricular Pacing Outcome Trial Evaluated for bradyCardia Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bradycardia
Pacing
Right Ventricular Pacing
His Bundle Pacing
Left Bundle Branch Area Pacing
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2023-04-18
Enrollment: 2600
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 PROTECT-HF multi-centre randomised controlled trial will compare two different pacing approaches for treating patients with slow heart rates. In it the investigators will compare a long-standing standard approach for pacing; right ventricular pacing, with a new form of pacing, physiological pacing (His and Left bundle area pacing) in 2600 patients.

Patients will be allocated at random to receive either right ventricular pacing or physiological pacing. Endpoint measurements will be undertaken at baseline, and at six-monthly intervals post-randomisation. Treatment allocation will be blinded to the endpoint assessor and the patient.

Recruitment and pacemaker implantation will be carried out at each participating centre. The primary analysis will be intention to treat. The investigators will also perform an on-treatment analysis.

2048 patients are needed to detect the expected effect size with 85% power. A total of 2600 patients will be recruited to allow for patient drop-out and crossover.

500-patient sub-study will assess within patient, and between groups, echocardiographic changes over a 24-month period to try and improve mechanistic understanding of PICM (Pacing Induced Cardiomyopathy).

Detailed description: Patients entering the study will attend for implantation of a pacemaker device and be randomised to either right ventricular pacing or physiological pacing.

Patients at sites participating in echo sub-study will be informed of and given opportunity to consent to echo sub-study, this will be optional to them, even if they have consented to the main study.

Eligibility criteria: We will recruit patients who are referred for clinically indicated pacemaker implantation

Inclusion Criteria:

1. Adults aged over 18 with left ventricular ejection fraction \>35% and one or more of the following guideline based ventricular pacing indications:

1. Permanent or intermittent 3rd degree AV block
2. Permanent or intermittent Mobitz type II AV block
3. First Degree AV block with a pacing indication
4. Slow chronic Atrial Fibrillation or Proposed AV node ablation
5. Bifascicular block with a pacing indication
6. Trifascicular block with a pacing indication
7. Wenckebach with a pacing indication

Exclusion Criteria:

1. Patients who are likely to only need occasional ventricular pacing, i.e. those with isolated sick sinus syndrome.
2. Pregnant women.
3. Unable to provide informed consent.
4. Those with comorbidity leading to a life expectancy \<1year.

Primary outcomes:
measure: Mortality
timeFrame: From date of consent, until date of death from any cause, assessed up until 78 months.
measure: Heart Failure Morbidity
timeFrame: From date of consent, assessed up until 78 months, or death from any cause, whichever came first.
Secondary outcomes:
measure: Incidence of clinically indicated upgrade to conventional biventricular pacing (CRT device)
timeFrame: From date of randomisation until the date of first documented incident of device upgrade, or death from any cause, whichever came first, assessed up to 78 months.
measure: Patient quality of life assessed via questionnaires (EQ-5D-5L) EQ-5D is the name of the instrument and is not an acronym.
timeFrame: From date of consent, assessed up to 78 months or until death of any cause, whichever came first.
measure: Patient symptoms assessed on a scale of 0-100 monthly
timeFrame: From one month after device implant date, assessed up to 78 months or until death of any cause, whichever came first.
measure: Safety endpoints: Device infections (requiring device extraction), pacing thresholds, need for lead revision or reimplantation, generator change, haematoma and pneumothorax
timeFrame: From device implant date, assessed up to 78 months or until death of any cause, whichever came first.
measure: Pacemaker derived endpoints: a) Atrial fibrillation (duration >6minutes) b) Ventricular arrhythmia incidence c) Daily patient activity (hours stratified by device vendor)
timeFrame: From device implant date, assessed up to 78 months or until death of any cause, whichever came first.
measure: Patient quality of life assessed via questionnaires '36-Item Short Form Health Survey' (SF-36)
timeFrame: From date of consent, assessed up to 78 months or until death of any cause, whichever came first.
measure: Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within group differences
timeFrame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).
measure: Echo Sub-Study Endpoint: Ejection Fraction (EF) within patient changes
timeFrame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).
measure: Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within patient changes
timeFrame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).
measure: Echo Sub-Study Endpoint: Ejection Fraction (EF) within group differences
timeFrame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Beacon Hospital
city: Ljubljana
country: Slovenia
facility: Univerisity Medical Centre Ljubljana
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Barking
country: United Kingdom
facility: Queen's Hospital
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bournemouth
country: United Kingdom
facility: University Hospital Dorset
city: Brighton
country: United Kingdom
facility: Royal SUSSEX County Hospital
city: Bristol
country: United Kingdom
facility: Bristol Heart Institute
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
city: Chichester
country: United Kingdom
facility: St Richard's Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Croydon
country: United Kingdom
facility: Croydon
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Fife Keith
country: United Kingdom
facility: Victoria Hospital
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: High Wycombe
country: United Kingdom
facility: Wycombe Hospital
city: Larbert
country: United Kingdom
facility: Forth Valley Royal Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Kettering Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Free London/ Barnet Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Watford General Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook Hospital
city: Nottingham
country: United Kingdom
facility: King's Mill Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire
city: Redhill
country: United Kingdom
facility: East Surrey
city: Rotherham
country: United Kingdom
facility: Rotherham General Hospital
city: Sheffield
country: United Kingdom
facility: Northern General
city: Slough
country: United Kingdom
facility: Wexham Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton
city: Swansea
country: United Kingdom
facility: Morriston Hospital
city: Swindon
country: United Kingdom
facility: Great Western
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital
city: Worthing
country: United Kingdom
facility: UHS Worthing
city: York
country: United Kingdom
facility: York Hospital
Study officials:
References: