Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades

Heart Failure Clinical Trial

— PROTECT-UP  

Official title:

Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06052475
• Other study ID #: 23HH8156
• Status: Recruiting
• Phase: N/A
• Start date: September 25, 2023
• Est. completion date: August 31, 2026

Study information

• Verified date: February 2024
• Source: Imperial College London
• Contact: Aya Khalil
• Phone: 07749576830
• Email: a.khalil[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: August 31, 2026
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bradycardia
• Cardiomyopathies
• Heart Failure
• Pacing-Induced Cardiomyopathy

Intervention

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.
• Continued RV Pacing (Right Ventricular Pacing)
Right ventricular pacing (apical or septal lead locations as per the implanting physicians' normal practice).

Locations

Country	Name	City	State
United Kingdom	Hammersmith Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SF-36 (Short Form 36 Health Survey Questionnaire) Physical Component Summary		From date of baseline, until end of trial follow-up at fourteen months post-baseline
Secondary	Left ventricular ejection fraction	(% ejection fraction)	From date of baseline, until end of trial follow-up at fourteen months
Secondary	Left ventricular end systolic volume	(millilitres)	From date of baseline, until end of trial follow-up at fourteen months
Secondary	Minnesota Living with Heart Failure Questionnaire		From date of baseline, until end of trial follow-up at fourteen months
Secondary	Six-minute walk test	Measured in distance in metres	From date of baseline, until end of trial follow-up at fourteen months
Secondary	Atrial fibrillation	(atrial fibrillation percentage burden as measured by pacemaker device - %)	From date of baseline, until end of trial follow-up at fourteen months
Secondary	Patient preference based on blinded symptomatic preference		At 2 months following baseline and 14 months following baseline visit
Secondary	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.	From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Secondary	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	From date of baseline, until end of trial follow-up at fourteen months post-baseline visit
Secondary	Safety endpoints	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)
Secondary	SF-36 (Short Form 36 Health Survey Questionnaire) Overall Score		From date of baseline, until end of trial follow-up at fourteen months post baseline visit
Secondary	SF-36 (Short Form 36 Health Survey Questionnaire) Individual Component Scores		From date of baseline, until end of trial follow-up at fourteen months post baseline visit
Secondary	BNP (B-type natriuretic peptide)	B-type natriuretic peptide blood test	From date of baseline, until end of trial follow-up at fourteen months post baseline visit