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

November 21, 2025 updated by: Imperial College London

Physiological vs Right Ventricular Pacing Outcome Trial Evaluated for bradyCardia Treatment

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

2600

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Ireland
      • Dublin, Ireland
  • Slovenia
      • Ljubljana, Slovenia
        • Recruiting
        • Univerisity Medical Centre Ljubljana
        • Contact:
        • Principal Investigator:
          • Dr David Zizek
  • United Kingdom
      • Aberdeen, United Kingdom
        • Recruiting
        • Aberdeen Royal Infirmary
        • Contact:
        • Principal Investigator:
          • Dr Santhosh Raga
      • Barking, United Kingdom
        • Recruiting
        • Queen's Hospital
        • Contact:
        • Principal Investigator:
          • Dr Afzal Sohaib
      • Birmingham, United Kingdom
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
        • Principal Investigator:
          • Prof Francisco Levya
      • Birmingham, United Kingdom
        • Recruiting
        • Good Hope Hospital
        • Contact:
        • Principal Investigator:
          • Dr Hossam Elsayed
      • Bournemouth, United Kingdom
        • Recruiting
        • University Hospital Dorset
        • Contact:
        • Principal Investigator:
          • Dr Girish Ganesha Babu
      • Brighton, United Kingdom
        • Recruiting
        • Royal Sussex County Hospital
        • Contact:
        • Principal Investigator:
          • Dr Susan Ellery
      • Bristol, United Kingdom
      • Cambridge, United Kingdom
        • Recruiting
        • Royal Papworth Hospital
        • Contact:
        • Principal Investigator:
          • Dr Sharad Agarwal
      • Chichester, United Kingdom
        • Recruiting
        • St Richard's Hospital
        • Contact:
        • Principal Investigator:
          • Dr Mark Tanner
      • Coventry, United Kingdom
        • Recruiting
        • University Hospital Coventry
        • Contact:
        • Principal Investigator:
          • Dr Michael Kuehl
      • Croydon, United Kingdom
      • Edinburgh, United Kingdom
      • Fife Keith, United Kingdom
        • Recruiting
        • Victoria Hospital
        • Contact:
        • Principal Investigator:
          • Dr Jagdeep Singh
      • Gillingham, United Kingdom
        • Recruiting
        • Medway Maritime Hospital
        • Contact:
        • Principal Investigator:
          • Dr Shaumik Adhya
      • High Wycombe, United Kingdom
        • Recruiting
        • Wycombe Hospital
        • Contact:
        • Principal Investigator:
          • Dr Norman Qureshi
      • Larbert, United Kingdom
        • Recruiting
        • Forth Valley Royal Hospital
        • Contact:
        • Principal Investigator:
          • Dr Gareth Padfield
        • Principal Investigator:
          • Dr Omar Fersia
      • Leeds, United Kingdom
      • Leicester, United Kingdom
      • Liverpool, United Kingdom
        • Recruiting
        • Liverpool Heart and Chest Hospital
        • Contact:
        • Principal Investigator:
          • Dr Archana Rao
      • London, United Kingdom
        • Recruiting
        • King's College Hospital
        • Contact:
        • Principal Investigator:
          • Dr Paul Scott
      • London, United Kingdom
      • London, United Kingdom
        • Recruiting
        • St Bartholomew's Hospital
        • Contact:
        • Principal Investigator:
          • Dr Phil Moore
      • London, United Kingdom
        • Recruiting
        • Kettering Hospital
        • Contact:
        • Principal Investigator:
          • Dr Rachana Prasad
      • London, United Kingdom
        • Recruiting
        • Royal Free London/ Barnet Hospital
        • Contact:
          • Susana Ramos Vasquez
        • Contact:
        • Principal Investigator:
          • Dr Joseph Tomson
      • London, United Kingdom
        • Recruiting
        • Watford General Hospital
        • Contact:
        • Principal Investigator:
          • Dr Louisa Malcome Lawes
      • Middlesbrough, United Kingdom
        • Recruiting
        • James Cook Hospital
        • Contact:
        • Principal Investigator:
          • Dr Mike Chapman
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham City Hospital
        • Principal Investigator:
          • Dr Phil Moore
        • Contact:
      • Nottingham, United Kingdom
        • Recruiting
        • King's Mill Hospital
        • Contact:
        • Principal Investigator:
          • Dr Sukh Bassi
      • Oxford, United Kingdom
        • Recruiting
        • John Radcliffe Hospital
        • Contact:
        • Principal Investigator:
          • Dr Julian Ormerod
      • Plymouth, United Kingdom
        • Recruiting
        • Derriford Hospital
        • Contact:
        • Principal Investigator:
          • Dr Edward Davies
      • Portsmouth, United Kingdom
      • Reading, United Kingdom
      • Redhill, United Kingdom
      • Rotherham, United Kingdom
        • Recruiting
        • Rotherham General Hospital
        • Contact:
        • Principal Investigator:
          • Dr Simon Smith
      • Sheffield, United Kingdom
        • Recruiting
        • Northern General
        • Contact:
        • Principal Investigator:
          • Dr Nigel Lewis
      • Slough, United Kingdom
        • Recruiting
        • Wexham Park Hospital
        • Contact:
        • Principal Investigator:
          • Dr Sofia Metaxa
      • Southampton, United Kingdom
      • Swansea, United Kingdom
      • Swindon, United Kingdom
        • Recruiting
        • Great Western
        • Contact:
        • Principal Investigator:
          • Dr Badri Chandrasekaran
      • Taunton, United Kingdom
      • Torquay, United Kingdom
        • Recruiting
        • Torbay Hospital
        • Contact:
        • Principal Investigator:
          • Dr Lisa Yung
      • Worthing, United Kingdom
      • York, United Kingdom
        • Recruiting
        • York Hospital
        • Contact:
        • Principal Investigator:
          • Dr Chris Hayes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Right ventricular pacing
Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice)
Device: Pacemaker - Right Ventricular pacing
Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice).
Experimental: 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 - 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: From date of consent, until date of death from any cause, assessed up until 78 months.
Death, any cause
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.
Adjudicated unplanned heart failure acute care (hospital admissions or ambulatory diuretic therapy i.e. diuretic lounge visit).
From date of consent, assessed up until 78 months, or death from any cause, whichever came first.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.

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.
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.
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.
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.
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.
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.
A high score defines a more favourable health state. Range 0 to 100.
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).
Within group differences of Left Ventricular End Systolic Volume (>10mls) for differences according to treatment allocation.
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).
Within patient changes in Ejection Fraction will be assessed for differences according to treatment allocation.
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).
Within patient changes of Left Ventricular End Systolic Volume (>10mls) for differences according to treatment allocation
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).
Within group differences in Ejection Fraction will be assessed for differences according to treatment allocation.
From baseline echocardiogram (0 to 6 weeks post pacemaker implant) to follow-up echocardiogram (24±1 months post pacemaker implant).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

British Heart Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2023

Primary Completion (Estimated)

December 4, 2029

Study Completion (Estimated)

December 4, 2029

Study Registration Dates

First Submitted

February 13, 2023

First Submitted That Met QC Criteria

April 4, 2023

First Posted (Actual)

April 18, 2023

Study Record Updates

Last Update Posted (Actual)

November 28, 2025

Last Update Submitted That Met QC Criteria

November 21, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22HH7931

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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