The His Optimised Pacing Evaluated for Heart Failure Trial (HOPE-HF).

Heart Failure Clinical 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02671903
• Other study ID #: 15HH2828
• Status: Completed
• Phase: N/A
• Start date: January 2016
• Est. completion date: October 31, 2020

Study information

• Verified date: December 2020
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Heart Failure

Intervention

Device:
• Pacemaker: AV optimised, His pacing.
Direct His bundle pacing: a Medtronic Select Secure 3830 pacing lead will be positioned at the His bundle. If selective direct His bundle pacing cannot be achieved then non-selective His bundle pacing will be accepted. AV delay optimisation: will be performed using acute non-invasive blood pressure acquired using the Finometer device (Finapres Medical systems, Netherlands).

Locations

Country	Name	City	State
United Kingdom	Basildon and Thurrock Hospitals NHS Foundation Trust	Basildon
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Western Sussex Hospitals NHS Foundation Trust	Chichester
United Kingdom	Medway NHS Foundation Trust	Gillingham
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	London
United Kingdom	Papworth Hospital NHS Foundation Trust	Papworth Everard
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Great Western Hospitals NHS Foundation Trust	Swindon
United Kingdom	West Hertfordshire Hospitals NHS Trust	Watford	Hertfordshire

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	British Heart Foundation, Medtronic

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in exercise capacity.	Measured using peak oxygen uptake (VO2).	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in Echocardiographic measurement of left ventricular function (Ejection Fraction)	Measured during echocardiogram.	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in B-type Naturietic Peptide (BNP).	Measured from blood sample.	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in Quality of Life Scores.	Measured using Quality of Life Questionnaire.	Baseline, 6 months and 12 months post randomisation.
Secondary	Cost effectiveness analysis (using a custom designed Resource Utilisation Questionnaire)	The analysis will be based on an intention-to-treat (ITT) principle. The economic evaluation will compare incremental costs and incremental outcomes of the direct His-bundle pacing against the standard medical care. The study will be performed from a societal perspective, which takes all relevant cost-categories and effects into account. The economic evaluation will consist of two parts, a cost-effectiveness analysis (CEA) and a cost utility analysis (CUA). In the CEA the incremental cost-effectiveness ratio (ICER) will be expressed as the incremental costs per point improvement in exercise capacity in peak VO2. The primary outcome measure in the CUA will be Qualitative Adjusted Life Years (QALYs), based on the EQ5D and Minnesota questionnaire scores.	Baseline.
Secondary	Changes in percentage pacing.	Measured during pacing check.	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in arrythmia burden (%).	Measured during pacing check.	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in pacing thresholds (Volts).	Measured during pacing check.	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in R wave amplitude.	Measured from electrocardiogram (ECG).	Baseline, 6 months and 12 months post randomisation.
Secondary	Changes in lead impedance (Ohms).	Measured during pacing check.	Baseline, 6 months and 12 months post randomisation.
Secondary	Fluoroscopy time during device insertion.	Measured by time in minutes.	Baseline.