Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades (PROTECT-UP)

July 8, 2024 updated by: Imperial College London

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

155

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

  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • Hammersmith Hospital
        • Contact:
          • Daniel Keene, PhD

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

Patients with an RV pacemaker and LVEF 35-50% who are clinically indicated for a cardiac resynchronisation therapy upgrade procedure and:

  1. EF reduced by >5% of increase in LVESV by 10ml since implant
  2. NT-proBNP >250ng/L in sinus rhythm
  3. NT-proBNP > 750 Ng/L if AF
  4. Left atrial volume index > 30ml/m2
  5. Regular loop diuretics prescribed
  6. Decline in daily patient activity by >1 hour per day since implant
  7. Decrease in device measured thoracic impedance
  8. Patient reported decline in functional class or exercise tolerance

Exclusion Criteria:

  • Those unable to provide informed consent
  • Patients under age 18
  • Pregnant women

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: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
From date of baseline, until end of trial follow-up at fourteen months post-baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction
Time Frame: From date of baseline, until end of trial follow-up at fourteen months
(% ejection fraction)
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
(millilitres)
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
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
Measured in distance in metres
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
(atrial fibrillation percentage burden as measured by pacemaker device - %)
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
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

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.
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
This questionnaire will be sent to participants on a monthly basis for the duration of the study
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)
Device infections (requiring device extraction), pacing thresholds, need for lead revision or reimplantation, generator change, haematoma and pneumothorax
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
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
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
B-type natriuretic peptide blood test
From date of baseline, until end of trial follow-up at fourteen months post baseline visit

Collaborators and Investigators

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

Sponsor

Imperial College London

Investigators

  • Principal Investigator: Daniel Keene, PhD, Imperial College London
  • Study Director: Nandita Kaza, MRCP, Imperial College London
  • Study Director: Matthew Shun-Shin, PhD, Imperial College London

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)

September 25, 2023

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

August 31, 2026

Study Registration Dates

First Submitted

September 19, 2023

First Submitted That Met QC Criteria

September 19, 2023

First Posted (Actual)

September 25, 2023

Study Record Updates

Last Update Posted (Actual)

July 10, 2024

Last Update Submitted That Met QC Criteria

July 8, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23HH8156

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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