Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades

Overview

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.

Interventions

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

Primary outcome measures

• 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]

Secondary outcome measures (12)

• 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]

Eligibility criteria

Patients with an RV pacemaker and LVEF 35-50% and a high burden of right ventricular pacing (>40%) who are clinically indicated for a cardiac resynchronisation therapy upgrade procedure and:

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

Exclusion criteria

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

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

Crossover

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United Kingdom · 12 centers

• Royal Papworth Hospital — Cambridge
• St. Richard's Hospital - University Hospitals Sussex — Chichester
• University Hospitals Coventry and Warwickshire NHS Trust, — Coventry
• Croydon University Hospital - Croydon Health Services — Croydon
• Glenfield Hospital — Leicester
• Hammersmith Hospital — London
• King's College Hospital — London
• St Bartholomew's Hospital - Barts Health NHS Trust — London
• … and 4 more centers

Identifiers

NCT: NCT06052475 · 23HH8156

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗