Comparing Three Types of Specialist Pacemakers to Improve Heart Function and Reduce Rhythm Problems in Heart Failure (RIPCORD-CRT)

Randomised Investigation of Physiological, Conventional and Optimised Resynchronisation Therapy in Heart Failure With Prolonged QRS Duration (RIPCORD-CRT)

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.

Study Overview

• Status: Recruiting
• Conditions: Dyssynchrony; Heart Failure and Reduced Ejection Fraction
• Intervention / Treatment: Device: Biventricular pacing; Device: Conduction system pacing; Device: Left bundle optimised cardiac resynchronisation therapy

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jack W Samways, MBChB, MRes, MRCP; Phone Number: +4420 331 33000; Email: jsamways@ic.ac.uk

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, W12 0HS
      • Recruiting
      • Hammersmith Hospital, Imperial College Healthcare NHS Trust
      • Contact: Jack W Samways, MBChB MRes (Merit) MRCP(UK); Phone Number: Ask for JWS +44 (0) 20 3311 3311; Email: jsamways@ic.ac.uk
      • Contact: Ahran D Arnold, MBBS BSc MSc MRCP PhD; Phone Number: Ask for ADA +44 (0) 20 3311 3311; Email: ada104@ic.ac.uk
      • Principal Investigator: Zachary I Whinnett, BMBS BMEDSCI MRCP PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Biventricular pacing; 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; Cardiac resynchronisation therapy with one lead to right ventricular endocardium and one lead to left ventricular epicardium, accessed via the coronary sinus.; Other Names: BVP
Experimental: Conduction system pacing; 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; 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.; Other Names: CSP; LBBAP; HBP; Physiological pacing; Left bundle branch pacing; Left bundle branch area pacing; Left septal pacing; His bundle pacing; LBBP; LSP
Experimental: Left bundle optimised cardiac resynchronisation therapy (LOT-CRT); 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; 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).; Other Names: LOT-CRT; His bundle optimised cardiac resynchronisation therapy; HOT-CRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Death; Intractable symptoms leading to trial exit/unblinding; Heart failure hospitalisation; Non-heart failure hospitalisation; Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device); 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: Death; Appropriate implantable cardioverter defibrillator therapy (anti-tachycardia pacing or shock, deemed appropriate as per clinical care team interrogating device); Sustained ventricular arrhythmia (VA) (>30s of rhythm determined to be ventricular in origin by clinical team on device interrogation); Sustained atrial arrhythmia; Non-sustained VA; >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: Death; Intractable symptoms leading to trial exclusion/unblinding; Heart failure hospitalisation; Non-heart failure hospitalisation; Left ventricular ejection fraction (measured on transthoracic echocardiogram)	From randomisation to 6-months post device implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of death	Death, any cause	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	Intractable symptoms leading to exit of trial considered to be a single event. Symptoms will be assessed routinely at a single remote consultation with a blinded research team member 1-4 months after device implant. If at this visit or after a patient directed consultation, symptoms are felt to have deteriorated after the device implant likely due to the device, the case will be discussed with the blinded principal-investigator to adjudicate. If the conclusion is that the deterioration is device mediated, the patient will be unblinded, exit from the trial and the device will be programmed to whatever is felt to be optimal by the clinical team.	From randomisation up to 36 months, or intractable symptoms leading to trial exit/unblinding, whichever came first.
Rate of heart failure hospitalisation	Adjudicated unplanned heart failure acute care (hospital admissions or ambulatory diuretic therapy i.e. diuretic lounge visit)	From randomisation up to 36 months
Rate of non-heart failure hospitalisation	Adjudicated unplanned non-heart failure acute care (hospital admissions or ambulatory service i.e. ambulatory emergency clinic).	From randomisation up to 36 months
Rate of appropriate implantable cardioverter defibrillator device therapy	Anti-tachycardia pacing or shock delivered by device adjudicated to be appropriate for ventricular arrhythmia	From randomisation up to 36 months
Daily heart failure symptom score	Bespoke mobile phone application based daily ordinal symptom score. Patients asked to identify their most associated heart failure symptom at the beginning of the study, they then grade that symptom on a 0-600 (non-labelled) continuum rating this symptom's severity for the previous day (0 being not limited at all, 600 being extremely limited).	From randomisation up to 36 months
Rate of sustained ventricular arrhythmia	Adjudicated sustained arrhythmia suspected to be ventricular in origin of >30s on device interrogation	From randomisation up to 36 months
Rate of sustained atrial arrhythmia	Adjudicated sustained arrhythmia suspected to be atrial in origin of >30s on device interrogation	From randomisation up to 36 months
Rate of non-sustained ventricular arrhythmia	Adjudicated non-sustained arrhythmia suspected to be ventricular in origin of <30s on device interrogation	From randomisation up to 36 months
Number of participants with >10% ventricular ectopy on 24h ECG		At 12-weeks post implant
Left ventricular ejection fraction (LVEF)	LVEF within group differences	From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months)
Left ventricular repolarisation heterogeneity	Non-invasive epicardial electrical mapping (ECGi) derived left ventricular repolarisation time and left ventricular repolarisation gradient	From implant to 6-months
Left ventricular activation	Non-invasive epicardial electrical mapping (ECGi) derived left ventricular activation time and left ventricular activation recovery interval	From implant to 6-months
QT dispersion	Measured from 24h ECG monitors patients are fitted with 12 weeks after device implant	From randomisation to 6 months post device implant
Left ventricular end diastolic volume (LVEDV)	LVEDV within group differences	From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months)
Left ventricular end systolic volume (LVESV)	LVESV within group differences	From baseline echocardiogram (pre device implant) to follow-up echocardiogram (at 6 months)
Six minute walk test	Within group comparison	From baseline to 6 months post device implantation
Serum B-type natriuretic peptide (BNP)	Within group comparison	From baseline to 6 months post device implant
Quality of life assessed via HeartQoL questionnaire	14 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart disease. Score between 0-42 with a lower score indicating worse quality of life.	From baseline to 6 months post device implant
Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12)	12 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart failure. Scores between 12-70 with the lower score suggesting a greater reduction in quality of life and worse symptoms.	From baseline to 6 months post device implant
Minnesota Living With Hearth Failure Questionnaire (MLWHFQ)	21 point questionnaire consisting of Likert scale answers to determine quality of life affected by heart disease. Scores between 0-125 with a lower score representing a better quality of life.	From baseline to 6 months post device implant
Heart failure status assessed by New York Heart Association classification		From baseline to 6 months post device implantation
Device derived patient activity level	Activity levels as measured by the implanted pacemaker generator.	At 6 months post device implant
Device determined atrial fibrillation burden	Proportion of time rhythm is atrial fibrillation as determined by implanted pacemaker detetection.	At 6 months post pacemaker implant
Percentage of days outside of the normal range device measured intrathoracic impedance or triggering device warning for fluid status	Taken from device checks at 3 and 6 months. Manufacturer specific defined alerts and intrathoracic normal ranges used, to allow to inter-manufacturer comparisons.	From implant to 6 months post pacemaker implant
Blinding index	Assessed using Bang Blinding Index (BBI), with patients asked regarding allocated treatment arm at the point of discharge following device implant and again before unblinding at 6 months. Scores will be allocated -1 for stating the incorrect treatment arm, 0 for the patient stating they do not know he treatment arm and +1 for a correctly stating the treatment arm.	From device implant, to 6 months post device implant
Number of patients with treatment related adverse events	Treatment related adverse events include; device infections (requiring device extraction or hospital admission), need for lead revision or reimplantation, premature generator change within study period, haematoma, pericardial effusion requiring intervention and pneumothorax. Other treatment related adverse events non included in this list, but adjudicated by trial steering committee may also be included.	From device implant to 36 months post device implant

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: Zachary I Whinnett, MBBS, BMedSci, MRCP, PhD, Imperial College London; Principal Investigator: Ahran D Arnold, MBBS, BSc, MSc, MRCP, PhD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2025
• Primary Completion (Estimated): October 24, 2028
• Study Completion (Estimated): October 24, 2028

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: heart failure; Cardiac resynchronisation therapy; Conduction system pacing; left bundle branch pacing; dyssynchrony; optimised CRT; LOT-CRT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Systolic; Therapeutics; Electric Stimulation Therapy; Cardiac Pacing, Artificial; Cardiac Resynchronization Therapy
• Other Study ID Numbers: 172375; FS/CRTF/25/24768 (Other Grant/Funding Number: British Heart Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No