Clinical trial NCT02671903: The His Optimised Pacing Evaluated for Heart Failure Trial (HOPE-HF).
Official title: AV Optimisation Delivered With Direct His Bundle Pacing, in Patients With Heart Failure, Long PR Without Left Bundle Branch Block: Randomised Multi-centre Clinical Outcome Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: Medtronic
First posted: 2016-02-02
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a multi-centre, prospective randomised double-blinded cross over study, recruiting a sub-population of patients with heart failure.

All patients will be implanted with a CRT (Cardiac Resynchronisation Therapy) pacemaker with one of the leads positioned on the His bundle in order to obtain direct His-bundle capture. There will be a 2-month run-in period where the device is not active.

A double-blinded cross-over design will then be employed to investigate the effect of His bundle pacing. Patients will be allocated in random order to six month treatment periods in each of the following two states (1) No pacing; (2) AV optimised direct His-bundle pacing. Endpoint measurements will be taken at baseline, 6 months and 12 months post randomisation. Treatment allocation will be blinded to the endpoint assessor and the patient.

126 patients will be needed to detect the expected effect size on the primary endpoint with 90% power. A total of 160 patients will be recruited to allow for patient drop-out.

Detailed description: Patients entering the study will attend for implantation of a CRT pacemaker device with one lead positioned on the His bundle. This will be performed either at the patient's local hospital or at Imperial College NHS healthcare Trust, no later than 4 months after the patient's screening visit.

All patients will be implanted with a Pacemaker or Implantable cardioverter defibrillator (ICD). In all patients a pacing lead will be positioned in the right atrium (typically the right atrial appendage). All patients will have a pacemaker lead positioned on the His bundle in order to obtain direct His-bundle capture. If it is not possible to successfully implant a His-bundle lead with selective direct His bundle capture or non-selective capture with \< 40ms prolongation of the QRS duration, then a lead will be implanted in a lateral branch of the coronary sinus.

In patients who do not have an indication for an Implantable cardioverter defibrillator (ICD) a second ventricular lead will be implanted in a lateral branch of the coronary sinus. If direct His pacing has not been successfully achieved then a further lead will be positioned at the RV apex. In patients who do have an indication for an Implantable cardioverter defibrillator the ICD lead will be positioned in the right ventricle (either RV apex or RV septum).

AV delay optimisation will be performed using acute non-invasive blood pressure acquired using the Finometer device (Finapres Medical systems, Netherlands). The BHF (British Heart Foundation) alternation protocol will be used in order to minimise the effect of background noise.

After implantation of the device there will be a 2 month run-in period prior to randomisation, the device will be programmed not to deliver His bundle pacing therapy during this period.(Back up only pacing and defibrillator function will be enabled).

Two months after patients are implanted with their device, patients will be randomised to either receive active pacing treatment or back up only pacing (pacemaker programmed to VVI 30 bpm). After a further 6 months they will be crossed over to the alternative treatment arm. Treatment allocation will be obtained using an Interactive Web Response System (IWRS) programmed with a randomisation schedule provided by the trial statistician. Appropriate blocking will be used.

Eligibility criteria: Inclusion Criteria:

* Aged 18 or above
* Ventricular Ejection Fraction (EF) \< 40%; BNP needs to be ≥250ng/L for patients with EF 36-40%
* New York Heart Association (NYHA) class II-IV
* PR interval ≥200ms
* Narrow QRS duration (≤140ms) or prolonged QRS duration with typical Right Bundle Branch Block (RBBB) morphology on 12 lead ECG and sinus rhythm

Exclusion Criteria:

* Permanent or persistent atrial fibrillation (AF)
* Paroxysmal atrial fibrillation with history of sustained AF (more than 24 hours) in the 6 months prior to screening
* Patients who are unable to perform cardiopulmonary exercise testing
* Other serious medical condition with life expectancy of less than 1 year
* Lack of capacity to consent
* Pregnancy
* Contraindication to use of the relevant study device or leads (as per current manuals from manufacturer)

Primary outcomes:
measure: Changes in Exercise Capacity.
timeFrame: Baseline, 6 months and 12 months post randomisation.
Secondary outcomes:
measure: Changes in Echocardiographic Measurement of Left Ventricular Function (Ejection Fraction)
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in B-type Naturietic Peptide (BNP).
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in Quality of Life Scores. - Minnesota
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Cost Effectiveness Analysis (Using a Custom Designed Resource Utilisation Questionnaire)
timeFrame: Baseline.
measure: Changes in Percentage Pacing
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in Arrythmia Burden (%).
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in Pacing Thresholds (Volts).
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in R Wave Amplitude.
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Changes in Lead Impedance (Ohms).
timeFrame: Baseline, 6 months and 12 months post randomisation.
measure: Fluoroscopy Time During Device Insertion.
timeFrame: Taken at Device Insertion Visit (2). Baseline measure.
measure: Changes in Quality of Life Scores. - EQ5D Health State Score
timeFrame: Baseline, 6 months and 12 months post randomisation.
Other outcomes:
Locations:
city: Watford
country: United Kingdom
facility: West Hertfordshire Hospitals NHS Trust
state: Hertfordshire
city: Basildon
country: United Kingdom
facility: Basildon and Thurrock Hospitals NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Chichester
country: United Kingdom
facility: Western Sussex Hospitals NHS Foundation Trust
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
city: Papworth Everard
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Swindon
country: United Kingdom
facility: Great Western Hospitals NHS Foundation Trust
Study officials:
affiliation: Senior Lecturer, Consultant Cardiologist and Electrophysiologist
name: Zachary Whinnett, BMBS MRCP
role: PRINCIPAL_INVESTIGATOR
References: