Pacing-Induced CardiomyopathyPROTECT-UPNCT06052475
Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades
A study testing Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing) and Continued RV Pacing (Right Ventricular Pacing) in people with Pacing-Induced Cardiomyopathy and Heart Failure, run by Imperial College London at 12 sites in United Kingdom.
Trial summary
Guidelines for patients having first-time implants advocate that even when heart function is only mildly impaired, modern pacing approaches should be utilised to avoid the potentially damaging effects of RV pacing to preventing symptoms from pacing induced or worsened cardiomyopathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pacing-Induced Cardiomyopathy, Heart Failure
- What is being tested?
- Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing) and Continued RV Pacing (Right Ventricular Pacing)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 12 sitesUnited Kingdom
- Study dates
- 4 Sep 2023to 4 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Those unable to provide informed consent
- Patients under age 18
- Pregnant women
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
United Kingdom12 sites, 12 recruiting
- Recruiting
Royal Papworth Hospital
Cambridge
Sharad Agarwal, sharad.agarwal@nhs.net
Sharad Agarwal
- Recruiting
St. Richard's Hospital - University Hospitals Sussex
Chichester
Mark Tanner, marktanner@nhs.net
Mark Tanner
- Recruiting
University Hospitals Coventry and Warwickshire NHS Trust,
Coventry
Michael Michael, Michael.Kuehl@uhcw.nhs.uk
Michael Kuehl
- Recruiting
Croydon University Hospital - Croydon Health Services
Croydon
Ravi Kamdar, ravi.kamdar@nhs.net
Ravi Kamdar
- Recruiting
Glenfield Hospital
Leicester
Ibrahim Mokhtar, mokhtar.ibrahim@uhl-tr.nhs.uk
Ibrahim Mokhtar
- Recruiting
Hammersmith Hospital
London
Daniel Keene, PhD
- Recruiting
King's College Hospital
London
Paul Scott, paulscott3@nhs.net
Paul Scott
- Recruiting
St Bartholomew's Hospital - Barts Health NHS Trust
London
Amal Muthumala, a.muthumala@nhs.net
Amal Muthumala
- Recruiting
Oxford University Hospitals
Oxford
Julian Ormerod, Julian.Ormerod@ouh.nhs.uk
Julian Ormerod
- Recruiting
University Hospitals Southampton
Southampton
John Paisey, john.paisey@uhs.nhs.uk
John Paisey
- Recruiting
Great Western Hospitals
Swindon
Badri Chandrasekaran, badri.chandrasekaran1@nhs.net
Badri Chandrasekaran
- Recruiting
Worthing Hospital - University Hospitals Sussex
Worthing
Marian Bencat, marian.bencat@nhs.net
Marian Bencat
About this study
Guidelines for patients having first-time implants advocate that even when heart function is only mildly impaired, modern pacing approaches should be utilised to avoid the potentially damaging effects of RV pacing to preventing symptoms from pacing induced or worsened cardiomyopathy.
However, once a traditional (RV) pacemaker is implanted, development of impaired heart function does not prompt a device upgrade. Even at the end of battery life, physicians simply replace it like-for-like.
Read more
This trial tests whether such patients have better symptoms and quality of life if changed to a modern physiological pacing strategy from the traditional RV pacing approach.
In this crossover trial, participants will be upgraded to a physiological pacing strategy.
After their procedure, they will have a one-month run-in period to recover from the procedure (their pacemaker will be programmed to continued RV pacing).
They will be have 2 one-month blinded time periods, randomised to physiological pacing or right ventricular pacing alternately. They will subsequently undergo two six-month blinded randomised time periods.
Patients will document symptoms monthly on a mobile phone application or computer. At the end of each time period, they will have measurements of heart function, a walking test and quality-of-life questionnaires including the SF-36 questionnaire.
The investigators hypothesise that upgrading to physiological pacing strategies will improve patients' quality of life.
- Conditions
- Pacing-Induced Cardiomyopathy, Heart Failure
- Being tested
- Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing), Continued RV Pacing (Right Ventricular Pacing)
- Keywords
- Physiological Pacing, RV Pacing, Biventricular Pacing, Pacemaker Upgrade
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing)Device
The approach for physiological pacing upgrade 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.
Continued RV Pacing (Right Ventricular Pacing)Device
Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice).
| Study group | Role | What they receive |
|---|---|---|
| Physiological Pacing (Conduction System Pacing or Biventricular Pacing) | Experimental | 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. Receives: Device: Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing) |
| Right Ventricular Pacing | Active comparator | Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice) Receives: Device: Continued RV Pacing (Right Ventricular Pacing) |
What is being measured
The primary outcome is the main question the study is designed to answer.
SF-36 (Short Form 36 Health Survey Questionnaire) Physical Component Summary
Measured: From date of baseline, until end of trial follow-up at fourteen months post-baseline
Secondary outcomes (12)
Left ventricular ejection fraction
(% ejection fraction)
Measured: From date of baseline, until end of trial follow-up at fourteen months
Left ventricular end systolic volume
(millilitres)
Measured: From date of baseline, until end of trial follow-up at fourteen months
Minnesota Living with Heart Failure Questionnaire
Measured: From date of baseline, until end of trial follow-up at fourteen months
Six-minute walk test
Measured in distance in metres
Measured: From date of baseline, until end of trial follow-up at fourteen months
Atrial fibrillation
(atrial fibrillation percentage burden as measured by pacemaker device - %)
Measured: From date of baseline, until end of trial follow-up at fourteen months
Patient preference based on blinded symptomatic preference
Measured: At 2 months following baseline and 14 months following baseline visit
EQ-5D Questionnaire
EQ-5D is the name of the instrument and is not an acronym. 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.
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.
Measured: From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Patient symptoms assessed on a scale of 0-100 monthly
This questionnaire will be sent to participants on a monthly basis for the duration of the study
Measured: From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Safety endpoints
Device infections (requiring device extraction), pacing thresholds, need for lead revision or reimplantation, generator change, haematoma and pneumothorax
Measured: From device implant date, assessed up to 15 months at the end of the trial (including a one-month run-in period post-procedure prior to the first baseline visit)
SF-36 (Short Form 36 Health Survey Questionnaire) Overall Score
Measured: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
SF-36 (Short Form 36 Health Survey Questionnaire) Individual Component Scores
Measured: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
BNP (B-type natriuretic peptide)
B-type natriuretic peptide blood test
Measured: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2023
- Study start4 Sep 2023
- Primary completion30 Sep 2026 (estimated)
- Study completion4 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pacing-Induced CardiomyopathyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Keene, PhD, Principal investigator, Imperial College LondonNandita Kaza, MRCP, Study director, Imperial College LondonMatthew Shun-Shin, PhD, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06052475
- Sponsor's protocol ID
- 23HH8156
- Acronym
- PROTECT-UP
- Status last verified
- Jun 2026
- First submitted
- 19 Sep 2023
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades
- ClinicalTrials.gov ID
- NCT06052475
- Acronym / sponsor ID
- PROTECT-UP / 23HH8156
- Conditions
- Pacing-Induced Cardiomyopathy, Heart Failure
- Keywords
- Physiological Pacing, RV Pacing, Biventricular Pacing, Pacemaker Upgrade
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 4 Sep 2023 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 4 Sep 2027 (estimated)
- First posted
- 25 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Guidelines for patients having first-time implants advocate that even when heart function is only mildly impaired, modern pacing approaches should be utilised to avoid the potentially damaging effects of RV pacing to preventing symptoms from pacing induced or worsened cardiomyopathy.
However, once a traditional (RV) pacemaker is implanted, development of impaired heart function does not prompt a device upgrade. Even at the end of battery life, physicians simply replace it like-for-like.
This trial tests whether such patients have better symptoms and quality of life if changed to a modern physiological pacing strategy from the traditional RV pacing approach.
In this crossover trial, participants will be upgraded to a physiological pacing strategy.
After their procedure, they will have a one-month run-in period to recover from the procedure (their pacemaker will be programmed to continued RV pacing).
They will be have 2 one-month blinded time periods, randomised to physiological pacing or right ventricular pacing alternately. They will subsequently undergo two six-month blinded randomised time periods.
Patients will document symptoms monthly on a mobile phone application or computer. At the end of each time period, they will have measurements of heart function, a walking test and quality-of-life questionnaires including the SF-36 questionnaire.
The investigators hypothesise that upgrading to physiological pacing strategies will improve patients' quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Physiological Pacing (Conduction System Pacing or Biventricular Pacing) | Experimental | Device: Physiological Pacing Upgrade (Conduction System Pacing or Biventricular 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. |
| Right Ventricular Pacing | Active comparator | Device: Continued RV Pacing (Right Ventricular Pacing)Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (3 listed)
- Those unable to provide informed consent
- Patients under age 18
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing)The approach for physiological pacing upgrade 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 | Physiological Pacing (Conduction System Pacing or Biventricular Pacing) |
| Continued RV Pacing (Right Ventricular Pacing)Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice). | Device | Right Ventricular Pacing |
Primary outcome
SF-36 (Short Form 36 Health Survey Questionnaire) Physical Component Summary
Time frame: From date of baseline, until end of trial follow-up at fourteen months post-baseline
12 secondary outcomes
Left ventricular ejection fraction
Time frame: From date of baseline, until end of trial follow-up at fourteen months
Left ventricular end systolic volume
Time frame: From date of baseline, until end of trial follow-up at fourteen months
Minnesota Living with Heart Failure Questionnaire
Time frame: From date of baseline, until end of trial follow-up at fourteen months
Six-minute walk test
Time frame: From date of baseline, until end of trial follow-up at fourteen months
Atrial fibrillation
Time frame: From date of baseline, until end of trial follow-up at fourteen months
Patient preference based on blinded symptomatic preference
Time frame: At 2 months following baseline and 14 months following baseline visit
EQ-5D Questionnaire
Time frame: From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Patient symptoms assessed on a scale of 0-100 monthly
Time frame: From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Safety endpoints
Time frame: From device implant date, assessed up to 15 months at the end of the trial (including a one-month run-in period post-procedure prior to the first baseline visit)
SF-36 (Short Form 36 Health Survey Questionnaire) Overall Score
Time frame: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
SF-36 (Short Form 36 Health Survey Questionnaire) Individual Component Scores
Time frame: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
BNP (B-type natriuretic peptide)
Time frame: From date of baseline, until end of trial follow-up at fourteen months post baseline visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Pacing-Induced Cardiomyopathy
Active, not recruiting
Physiological Pacing for AV Block to Prevent Pacemaker-induced Cardiomyopathy
Conduction System Pacing, Conventional Ventricular Pacing
RecruitingObservational study
Patient Selection and Long-Term Outcomes of Pace & Ablate Strategy in Atrial Fibrillation
Atrial Fibrillation (AF), Cardiomyopathy, Secondary
RecruitingObservational study
Pacing Advancements With Cost and Experience VALuation for Unified Patient-Led Clinical Evidence - the PACEVALUE Study
Cardiomyopathy, Secondary, Arrhythmias, Cardiac
Not yet recruiting
Procedural Endpoint in Left Bundle Branch Area Pacing: Conduction System Capture Versus LV Septal Capture
Bradycardia, Atrioventricular Block
RecruitingObservational study
Comparing the Effects of Newer Pacemakers and Their Effects on the Heart and Valve Function in the Short-term.
Pacemaker-Induced Cardiomyopathy, Tricuspid Regurgitation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Keene, PhD principal investigator
Imperial College London
Nandita Kaza, MRCP study director
Imperial College London
Matthew Shun-Shin, PhD study director
Imperial College London
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Physiological Pacing Upgrade (Conduction System Pacing or Biventricular Pacing) and Continued RV Pacing (Right Ventricular Pacing) in people with Pacing-Induced Cardiomyopathy and Heart Failure, run by Imperial College London at 12 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aya Khalil (07749576830, a.khalil@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SF-36 (Short Form 36 Health Survey Questionnaire) Physical Component Summary (time frame: From date of baseline, until end of trial follow-up at fourteen months post-baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.