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| ID | Type | Description | Link |
|---|---|---|---|
| FS/CRTF/25/24768 | Other Grant/Funding Number | British Heart Foundation |
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| Name | Class |
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| Imperial College Healthcare NHS Trust | OTHER |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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. |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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:
| From randomisation to 6-months post device implant |
| Primary arrhythmia outcome | Ordinal arrhythmia scale using clinical endpoints as detailed below:
| From randomisation to 6-months post device implant |
| Primary contractility outcome | Ordinal contractility scale using clinical endpoints as detailed below:
| From randomisation to 6-months post device implant |
| 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 |
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Inclusion Criteria:
Patients referred/scheduled for a CRT procedure (new implant or upgrade) who have:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jack W Samways, MBChB, MRes, MRCP | Contact | +4420 331 33000 | jsamways@ic.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Hospital, Imperial College Healthcare NHS Trust | Recruiting | London | Greater London | W12 0HS | United Kingdom |
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3-arm parallel (1:1:1) study
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| 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. |
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| 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). |
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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 |
| ID | Term |
|---|---|
| D054143 | Heart Failure, Systolic |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D058406 | Cardiac Resynchronization Therapy |
| ID | Term |
|---|---|
| D002304 | Cardiac Pacing, Artificial |
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
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