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"Physiological vs Right Ventricular Pacing Outcome Trial Evaluated for bradyCardia Treatment" (PROTECT-HF)

Not Applicable
Recruiting
Conditions
Right Ventricular Pacing
Bradycardia
Pacing
His Bundle Pacing
Left Bundle Branch Area Pacing
Interventions
Device: Pacemaker - Physiological pacing
Device: Pacemaker - Right Ventricular pacing
Registration Number
NCT05815745
Lead Sponsor
Imperial College London
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2600
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:

  2. Permanent or intermittent 3rd degree AV block

  3. Permanent or intermittent Mobitz type II AV block

  4. First Degree AV block with a pacing indication

  5. Slow chronic Atrial Fibrillation or Proposed AV node ablation

  6. Bifascicular block with a pacing indication

  7. Trifascicular block with a pacing indication

  8. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Physiological pacingPacemaker - Physiological pacingThe approach for physiological pacing will be either His bundle pacing or left bundle pacing at the operator's discretion. If both of these are not achieved biventricular pacing will be performed.
Right ventricular pacingPacemaker - Right Ventricular pacingRight ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice)
Primary Outcome Measures
NameTimeMethod
Heart Failure MorbidityFrom date of consent, assessed up until 78 months, or death from any cause, whichever came first.

Adjudicated unplanned heart failure acute care (hospital admissions or ambulatory diuretic therapy i.e. diuretic lounge visit).

MortalityFrom date of consent, until date of death from any cause, assessed up until 78 months.

Death, any cause

Secondary Outcome Measures
NameTimeMethod
Safety endpoints: Device infections (requiring device extraction), pacing thresholds, need for lead revision or reimplantation, generator change, haematoma and pneumothoraxFrom device implant date, assessed up to 78 months or until death of any cause, whichever came first.
Incidence of clinically indicated upgrade to conventional biventricular pacing (CRT device)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.
Patient symptoms assessed on a scale of 0-100 monthlyFrom one month after device implant date, assessed up to 78 months or until death of any cause, whichever came first.

This questionnaire will be sent to participants on a monthly basis for the duration of the study, 78 months from one month post pacemaker implant until end of study (78 months) or death from any cause, whichever came first.

Patient quality of life assessed via questionnaires (EQ-5D-5L) EQ-5D is the name of the instrument and is not an acronym.From date of consent, assessed up to 78 months or until death of any cause, whichever came first.

The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ 'visual analogue scale' (EQ VAS).

The descriptive system is made up of 5 sections: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.

A High score on the descriptive section means a worse health outcome. A Low score on the descriptive section means a better health outcome. A value set is required to convert the outcomes into scores.

The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative (numerical) measure of health outcome that reflect the patient's own judgement.

A high score on the VAS means a better outcome. A low score on the VAS means a worse outcome.

Pacemaker derived endpoints: a) Atrial fibrillation (duration >6minutes) b) Ventricular arrhythmia incidence c) Daily patient activity (hours stratified by device vendor)From device implant date, assessed up to 78 months or until death of any cause, whichever came first.
Patient quality of life assessed via questionnaires '36-Item Short Form Health Survey' (SF-36)From date of consent, assessed up to 78 months or until death of any cause, whichever came first.

A high score defines a more favourable health state. Range 0 to 100.

Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within patient changesFrom baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).

Within patient changes of Left Ventricular End Systolic Volume (\>10mls) for differences according to treatment allocation

Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within group differencesFrom baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).

Within group differences of Left Ventricular End Systolic Volume (\>10mls) for differences according to treatment allocation.

Echo Sub-Study Endpoint: Ejection Fraction (EF) within patient changesFrom baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).

Within patient changes in Ejection Fraction will be assessed for differences according to treatment allocation.

Echo Sub-Study Endpoint: Ejection Fraction (EF) within group differencesFrom baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).

Within group differences in Ejection Fraction will be assessed for differences according to treatment allocation.

Trial Locations

Locations (45)

Hammersmith Hospital

🇬🇧

London, United Kingdom

Good Hope Hospital

🇬🇧

Birmingham, United Kingdom

University Hospital Dorset

🇬🇧

Bournemouth, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

Bristol Heart Institute

🇬🇧

Bristol, United Kingdom

Wycombe Hospital

🇬🇧

High Wycombe, United Kingdom

Liverpool Heart and Chest Hospital

🇬🇧

Liverpool, United Kingdom

Derriford Hospital

🇬🇧

Plymouth, United Kingdom

Royal Berkshire

🇬🇧

Reading, United Kingdom

Wexham Park Hospital

🇬🇧

Slough, United Kingdom

Southampton

🇬🇧

Southampton, United Kingdom

Morriston Hospital

🇬🇧

Swansea, United Kingdom

Royal SUSSEX County Hospital

🇬🇧

Brighton, United Kingdom

St Richard's Hospital

🇬🇧

Chichester, United Kingdom

King's Mill Hospital

🇬🇧

Nottingham, United Kingdom

St Bartholomew's Hospital

🇬🇧

London, United Kingdom

Watford General Hospital

🇬🇧

London, United Kingdom

Torbay Hospital

🇬🇧

Torquay, United Kingdom

York Hospital

🇬🇧

York, United Kingdom

Queen's Hospital

🇬🇧

Barking, United Kingdom

Aberdeen Royal Infirmary

🇬🇧

Aberdeen, United Kingdom

Royal Infirmary of Edinburgh

🇬🇧

Edinburgh, United Kingdom

Victoria Hospital

🇬🇧

Fife Keith, United Kingdom

Royal Papworth Hospital

🇬🇧

Cambridge, United Kingdom

Croydon

🇬🇧

Croydon, United Kingdom

Medway Maritime Hospital

🇬🇧

Gillingham, United Kingdom

University Hospital Coventry

🇬🇧

Coventry, United Kingdom

Leeds Teaching Hospital

🇬🇧

Leeds, United Kingdom

Forth Valley Royal Hospital

🇬🇧

Larbert, United Kingdom

Glenfield Hospital

🇬🇧

Leicester, United Kingdom

King's College Hospital

🇬🇧

London, United Kingdom

Royal Free London/ Barnet Hospital

🇬🇧

London, United Kingdom

Kettering Hospital

🇬🇧

London, United Kingdom

Nottingham City Hospital

🇬🇧

Nottingham, United Kingdom

James Cook Hospital

🇬🇧

Middlesbrough, United Kingdom

John Radcliffe Hospital

🇬🇧

Oxford, United Kingdom

Queen Alexandra Hospital

🇬🇧

Portsmouth, United Kingdom

Northern General

🇬🇧

Sheffield, United Kingdom

East Surrey

🇬🇧

Redhill, United Kingdom

Rotherham General Hospital

🇬🇧

Rotherham, United Kingdom

Great Western

🇬🇧

Swindon, United Kingdom

Musgrove Park Hospital

🇬🇧

Taunton, United Kingdom

UHS Worthing

🇬🇧

Worthing, United Kingdom

Beacon Hospital

🇮🇪

Dublin, Ireland

Univerisity Medical Centre Ljubljana

🇸🇮

Ljubljana, Slovenia

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