Comparing Three Types of Specialist Pacemakers to Improve Heart Function and Reduce Rhythm Problems in Heart Failure

NCT07430553 | Recruiting DMC

• 2 other identifiers: 172375FS/CRTF/25/24768
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to find out which type of specialist pacemaker-known as cardiac resynchronisation therapy (CRT)-works best for people with heart failure and a delay in how the lower chambers of the heart beat together (called electrical dyssynchrony). The main aims of the study are: To compare the effects of conventional biventricular pacing (BVP), conduction system pacing (CSP) and left-bundle optimised CRT (LOT-CRT) on heart failure symptoms and heart rhythm problems over six months. To explore how these pacing methods affect heart muscle strength, electrical activity, and overall heart function. Participants will: Attend four hospital visits over a six-month period. At Visit 1, meet a member of the research team to discuss the study and have screening tests to check eligibility. Participants will also have a smartphone app installed and receive training on how to record their daily heart failure symptoms. At Visit 2, have a CRT pacemaker implanted. The type of pacemaker will be chosen at random, with a 1 in 3 chance of receiving:

• Biventricular pacing (BVP); the current standard treatment
• Conduction system pacing (CSP)
• LOT-CRT (Left-bundle optimised CRT); a combination of both At Visit 3 (around 12 weeks after implantation) and Visit 4 (6 months after implantation), take part in routine follow-up assessments to check the pacemaker and heart function. At Visits 2 and 4, also undergo non-invasive electrical mapping tests, including wearing a specialised vest and having a low-dose CT scan of the chest. These tests help researchers understand how the heart's electrical system responds to different pacing methods.

Conditions

Heart Failure and Reduced Ejection Fraction; Dyssynchrony

Keywords

Cardiac resynchronisation therapy; Conduction system pacing; optimised CRT; LOT-CRT; heart failure; dyssynchrony; left bundle branch pacing

Outcome Measures

Primary Outcomes (3)

• Primary outcome: Daily ordinal symptom score with clinical over-rides

  Daily ordinal scale with mobile application based assessment of quality of life (using visual analogue scale), with clinical over-rides as detailed below: 1. Death 2. Intractable symptoms leading to trial exit/unblinding 3. Heart failure hospitalisation 4. Non-heart failure hospitalisation 5. Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device) 6. Symptom score (1-600, with 1 representing minimum limitation from patient ascribed heart failure symptom and 600 representing maximum limitation)

  From randomisation to 6-months post device implant

• Primary arrhythmia outcome

  Ordinal arrhythmia scale using clinical endpoints as detailed below: 1. Death 2. Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device) 3. Sustained ventricular arrhythmia (VA) (\>30s of rhythm determined to be ventricular in origin by clinical team on device interrogation) 4. Sustained atrial arrhythmia 5. Non-sustained VA 6. \>10% ventricular ectopy on 24h ECG

  From randomisation to 6-months post device implant

• Primary contractility outcome

  Ordinal contractility scale using clinical endpoints as detailed below: 1. Death 2. Intractable symptoms leading to trial exclusion/unblinding 3. Heart failure hospitalisation 4. Non-heart failure hospitalisation 5. Left ventricular ejection fraction (measured on transthoracic echocardiogram)

  From randomisation to 6-months post device implant

Secondary Outcomes (27)

• Rate of death

  From randomisation up to 36 months, or death from any cause, whichever came first.

• Number of participants with intractable symptoms leading to trial exit/unblinding

  From randomisation up to 36 months, or intractable symptoms leading to trial exit/unblinding, whichever came first.

• Rate of heart failure hospitalisation

  From randomisation up to 36 months

• Rate of non-heart failure hospitalisation

  From randomisation up to 36 months

• Rate of appropriate implantable cardioverter defibrillator device therapy

  From randomisation up to 36 months

Study Arms (3)

Biventricular pacing

ACTIVE COMPARATOR

Current standard of care cardiac resynchronisation therapy with biventricular pacing (one lead to right ventricular endocardium and one lead to left ventricular epicardium, accessed via the coronary sinus).

Device: Biventricular pacing

Conduction system pacing

EXPERIMENTAL

Cardiac resynchronisation therapy with single lead targeting direct capture of the conduction system. Primary target should be left bundle area, with backup target of His bundle.

Device: Conduction system pacing

Left bundle optimised cardiac resynchronisation therapy (LOT-CRT)

EXPERIMENTAL

Cardiac resynchronisation therapy delivered by conduction system optimised hybrid configurations. Primary configuration should be conduction system pacing lead targeted at the left bundle area combined with left ventricular epicardial lead accessed via the coronary sinus (LOT-CRT). Backup configuration of conduction system pacing lead targeted at the His bundle combined with left ventricular epicardial lead accessed via the coronary sinus (HOT-CRT).

Device: Left bundle optimised cardiac resynchronisation therapy

Interventions

Biventricular pacing DEVICE

Cardiac resynchronisation therapy with one lead to right ventricular endocardium and one lead to left ventricular epicardium, accessed via the coronary sinus.

Also known as: BVP

Biventricular pacing

Conduction system pacing DEVICE

Cardiac resynchronisation therapy with single lead targeting direct capture of the conduction system. Primary target should be left bundle area, with backup target of His bundle. If direct capture of the conduction system cannot be achieved by conventional clinical criteria, left septal pacing targeted at the left bundle branch area will be accepted.

Also known as: Physiological pacing, CSP, Left bundle branch pacing, Left bundle branch area pacing, Left septal pacing, His bundle pacing, LBBP, LBBAP, LSP, HBP

Conduction system pacing

Left bundle optimised cardiac resynchronisation therapy DEVICE

Cardiac resynchronisation therapy delivered by conduction system optimised hybrid configurations. Primary configuration should be conduction system pacing lead targeted at the left bundle area combined with left ventricular epicardial lead accessed via the coronary sinus (LOT-CRT). Backup configuration of conduction system pacing lead targeted at the His bundle combined with left ventricular epicardial lead accessed via the coronary sinus (HOT-CRT).

Also known as: LOT-CRT, His bundle optimised cardiac resynchronisation therapy, HOT-CRT

Left bundle optimised cardiac resynchronisation therapy (LOT-CRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients referred/scheduled for a CRT procedure (new implant or upgrade) who have:
• Symptomatic heart failure (NYHA II-IV)
• Reduced ejection fraction (LVEF≤40%)
• Prolonged QRS duration (≥130ms) and left bundle branch block ECG morphology or very prolonged QRS duration (\>150ms) and non-left bundle branch block ECG
• Optimal medical therapy for HF

You may not qualify if:

• Unable to provide informed consent
• \<18 years old
• Pregnant patients (with female patients of childbearing age requiring a negative urine BHCG)

Sponsors & Collaborators

• Imperial College London: lead
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

Hammersmith Hospital, Imperial College Healthcare NHS Trust

London, Greater London, W12 0HS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Heart Failure, Systolic; Heart Failure

Interventions

Cardiac Resynchronization Therapy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Pacing, Artificial; Electric Stimulation Therapy; Therapeutics

Study Officials

• Zachary I Whinnett, MBBS, BMedSci, MRCP, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Ahran D Arnold, MBBS, BSc, MSc, MRCP, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jack W Samways, MBChB, MRes, MRCP

CONTACT

+4420 331 33000; jsamways@ic.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3-arm parallel (1:1:1) study

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: February 24, 2026
• Study Start: November 12, 2025
• Primary Completion (Estimated): October 24, 2028
• Study Completion (Estimated): October 24, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

GB (1)