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

December 2, 2020 updated by: Imperial College London

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

198

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Basildon, United Kingdom
        • Basildon and Thurrock Hospitals NHS Foundation Trust
      • Birmingham, United Kingdom
        • University Hospitals Birmingham NHS Foundation Trust
      • Bristol, United Kingdom
        • University Hospitals Bristol NHS Foundation Trust
      • Chichester, United Kingdom
        • Western Sussex Hospitals NHS Foundation Trust
      • Gillingham, United Kingdom
        • Medway Nhs Foundation Trust
      • Leicester, United Kingdom
        • University Hospitals of Leicester NHS Trust
      • London, United Kingdom, W12 0HS
        • Hammersmith Hospital
      • London, United Kingdom
        • Barts Health NHS Trust
      • London, United Kingdom
        • King's College Hospital NHS Foundation Trust
      • London, United Kingdom
        • Guy's and St Thomas' NHS Foundation Trust
      • London, United Kingdom
        • Royal Brompton & Harefield NHS Foundation Trust
      • Papworth Everard, United Kingdom
        • Papworth Hospital NHS Foundation Trust
      • Sheffield, United Kingdom
        • Sheffield Teaching Hospitals NHS Foundation Trust
      • Swindon, United Kingdom
        • Great Western Hospitals NHS Foundation Trust
    • Hertfordshire
      • Watford, Hertfordshire, United Kingdom, WD18 0HB
        • West Hertfordshire Hospitals Nhs Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pacemaker: AV optimised, His pacing
Subjects will remain in this arm for 6 months before being crossed-over. See below intervention details.
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).
No Intervention: No pacing
Subjects will remain in this arm for 6 months before being crossed-over. The pacemaker will be programmed to VVI 30 bpm. Dynamic AV delay will be programmed off throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in exercise capacity.
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured using peak oxygen uptake (VO2).
Baseline, 6 months and 12 months post randomisation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Echocardiographic measurement of left ventricular function (Ejection Fraction)
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured during echocardiogram.
Baseline, 6 months and 12 months post randomisation.
Changes in B-type Naturietic Peptide (BNP).
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured from blood sample.
Baseline, 6 months and 12 months post randomisation.
Changes in Quality of Life Scores.
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured using Quality of Life Questionnaire.
Baseline, 6 months and 12 months post randomisation.
Cost effectiveness analysis (using a custom designed Resource Utilisation Questionnaire)
Time Frame: Baseline.
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.
Changes in percentage pacing.
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured during pacing check.
Baseline, 6 months and 12 months post randomisation.
Changes in arrythmia burden (%).
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured during pacing check.
Baseline, 6 months and 12 months post randomisation.
Changes in pacing thresholds (Volts).
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured during pacing check.
Baseline, 6 months and 12 months post randomisation.
Changes in R wave amplitude.
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured from electrocardiogram (ECG).
Baseline, 6 months and 12 months post randomisation.
Changes in lead impedance (Ohms).
Time Frame: Baseline, 6 months and 12 months post randomisation.
Measured during pacing check.
Baseline, 6 months and 12 months post randomisation.
Fluoroscopy time during device insertion.
Time Frame: Baseline.
Measured by time in minutes.
Baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Medtronic
British Heart Foundation

Investigators

  • Principal Investigator: Zachary Whinnett, BMBS MRCP, Senior Lecturer, Consultant Cardiologist and Electrophysiologist

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

October 31, 2020

Study Completion (Actual)

October 31, 2020

Study Registration Dates

First Submitted

January 26, 2016

First Submitted That Met QC Criteria

January 29, 2016

First Posted (Estimate)

February 2, 2016

Study Record Updates

Last Update Posted (Actual)

December 3, 2020

Last Update Submitted That Met QC Criteria

December 2, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15HH2828

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All IPD that underlie results in a publication. The data set will be created as an anonymised data sharing package and will be available post publication of data.

IPD Sharing Time Frame

6 months post publication of data

IPD Sharing Access Criteria

The anonymised data set will be shared with the journal in which the papers are published.

We will make the data available for analysis by non-commercial researchers on request to the Chief investigator.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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