"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

Overview

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.

Interventions

• Device Pacemaker - Physiological pacing
  The 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.
• Device Pacemaker - Right Ventricular pacing
  Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice).

Primary outcome measures

• Mortality [Time frame: From date of consent, until date of death from any cause, assessed up until 78 months.]
• Heart Failure Morbidity [Time frame: From date of consent, assessed up until 78 months, or death from any cause, whichever came first.]

Secondary outcome measures (10)

• Incidence of clinically indicated upgrade to conventional biventricular pacing (CRT device) [Time frame: 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 quality of life assessed via questionnaires (EQ-5D-5L) EQ-5D is the name of the instrument and is not an acronym. [Time frame: From date of consent, assessed up to 78 months or until death of any cause, whichever came first.]
• Patient symptoms assessed on a scale of 0-100 monthly [Time frame: From one month after device implant date, assessed up to 78 months or until death of any cause, whichever came first.]
• Safety endpoints: Device infections (requiring device extraction), pacing thresholds, need for lead revision or reimplantation, generator change, haematoma and pneumothorax [Time frame: From device implant date, assessed up to 78 months or until death of any cause, whichever came first.]
• Pacemaker derived endpoints: a) Atrial fibrillation (duration >6minutes) b) Ventricular arrhythmia incidence c) Daily patient activity (hours stratified by device vendor) [Time frame: 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) [Time frame: From date of consent, assessed up to 78 months or until death of any cause, whichever came first.]
• Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within group differences [Time frame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).]
• Echo Sub-Study Endpoint: Ejection Fraction (EF) within patient changes [Time frame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).]
• Echo Sub-Study Endpoint: Left Ventricular End Systolic Volume (LVESV) (>10mls) within patient changes [Time frame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).]
• Echo Sub-Study Endpoint: Ejection Fraction (EF) within group differences [Time frame: From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).]

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:

• Permanent or intermittent 3rd degree AV block
• Permanent or intermittent Mobitz type II AV block
• First Degree AV block with a pacing indication
• Slow chronic Atrial Fibrillation or Proposed AV node ablation
• Bifascicular block with a pacing indication
• Trifascicular block with a pacing indication
• Wenckebach with a pacing indication

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United Kingdom · 43 centers

• Aberdeen Royal Infirmary — Aberdeen
• Queen's Hospital — Barking
• Good Hope Hospital — Birmingham
• Queen Elizabeth Hospital — Birmingham
• University Hospital Dorset — Bournemouth
• Royal SUSSEX County Hospital — Brighton
• Bristol Heart Institute — Bristol
• Royal Papworth Hospital — Cambridge
• … and 35 more centers

Ireland · 1 center

• Beacon Hospital — Dublin

Slovenia · 1 center

• Univerisity Medical Centre Ljubljana — Ljubljana

Identifiers

NCT: NCT05815745 · 22HH7931

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗