Heart FailureHOPE-HFNCT02671903
The His Optimised Pacing Evaluated for Heart Failure Trial (HOPE-HF).
A study testing Pacemaker: AV optimised, His pacing. in people with Heart Failure, run by Imperial College London at 15 sites in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Pacemaker: AV optimised, His pacing.
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 15 sitesUnited Kingdom
- Study dates
- Jan 2016to 31 Oct 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United Kingdom15 sites
Basildon and Thurrock Hospitals NHS Foundation Trust
Basildon
University Hospitals Birmingham NHS Foundation Trust
Birmingham
University Hospitals Bristol NHS Foundation Trust
Bristol
Western Sussex Hospitals NHS Foundation Trust
Chichester
Medway NHS Foundation Trust
Gillingham
University Hospitals of Leicester NHS Trust
Leicester
Hammersmith Hospital
London, W12 0HS
Barts Health NHS Trust
London
Guy's and St Thomas' NHS Foundation Trust
London
King's College Hospital NHS Foundation Trust
London
Royal Brompton & Harefield NHS Foundation Trust
London
Papworth Hospital NHS Foundation Trust
Papworth Everard
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield
Great Western Hospitals NHS Foundation Trust
Swindon
West Hertfordshire Hospitals NHS Trust
Watford, Hertfordshire, WD18 0HB
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Pacemaker: AV optimised, His pacing.
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pacemaker: AV optimised, His pacing.Device
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).
| Study group | Role | What they receive |
|---|---|---|
| Pacemaker: AV optimised, His pacing | Active comparator | Subjects will remain in this arm for 6 months before being crossed-over. See below intervention details. Receives: Device: Pacemaker: AV optimised, His pacing. |
| No pacing | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
Changes in Exercise Capacity.
Measured using peak oxygen uptake (VO2).
Measured: Baseline, 6 months and 12 months post randomisation.
Secondary outcomes (11)
Changes in Echocardiographic Measurement of Left Ventricular Function (Ejection Fraction)
Measured during echocardiogram.
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in B-type Naturietic Peptide (BNP).
Measured from blood sample. Note: BNP was log-transformed before analysis in the mixed-model and then back transformed for presentation
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in Quality of Life Scores. - Minnesota
Measured using Minnesota Score obtained from the Minnesota Living with Heart Failure Questionnaire (MLHFQ).
Score range: 0 to 105, with higher scores indicating a worse outcome with more significant impairment in health-related quality of life
Measured: Baseline, 6 months and 12 months post randomisation.
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.
NOTE: Cost effectiveness was unable to be completed for HOPE-HF and as such null results are displayed
Measured: Baseline.
Changes in Percentage Pacing
Measured at completion of periods 1 \& 2 (M6 \& M12) - Percentage of time where device recorded ventricular pacing during each treatment period. Values are recorded across both arms.
Results are descriptive and displayed by treatment and by period.
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in Arrythmia Burden (%).
Measured upon completion of run-in (as baseline) and periods 1 \& 2 (M6 \& M12). Device detected Atrial Fibrillation/Supraventricular Tachycardia (AF/SVT) burden recorded as a percentage of time over the 6-month treatment period.
Results are descriptive and displayed by treatment and by period.
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in Pacing Thresholds (Volts).
Measured upon completion of run-in and periods 1 \& 2 (BL, M6 \& M12)
Results are descriptive and displayed by treatment and by period. Please also note that voltage is presented for both RA Lead and LV Lead.
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in R Wave Amplitude.
Measured from electrocardiogram (ECG).
Measured: Baseline, 6 months and 12 months post randomisation.
Changes in Lead Impedance (Ohms).
Measured upon completion of run-in and periods 1 \& 2 (BL, M6 \& M12).
Results are descriptive and displayed by treatment and by period. Please also note that lead impedance is presented for both RA Lead, HIS-Lead and LV Lead.
Measured: Baseline, 6 months and 12 months post randomisation.
Fluoroscopy Time During Device Insertion.
Measured by time in minutes.
Measured: Taken at Device Insertion Visit (2). Baseline measure.
Changes in Quality of Life Scores. - EQ5D Health State Score
Taken from the Visual Analog Scale (VAS) Score from EQ5D Health State Question in EuroQol, 5-dimension, 5-level (EQ5D5L) questionnaire.
Score is on a 0-100 scale with 100 representing a better outcome for patients health state.
Measured: Baseline, 6 months and 12 months post randomisation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2016 (estimated)
- Study startJan 2016
- Primary completion31 Oct 2020
- Study completion31 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Medtronic
- Responsible party
- Sponsor
- Investigators
- Zachary Whinnett, BMBS MRCP, Principal investigator, Senior Lecturer, Consultant Cardiologist and Electrophysiologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02671903
- Sponsor's protocol ID
- 15HH2828
- Acronym
- HOPE-HF
- Status last verified
- Jan 2025
- First submitted
- 26 Jan 2016
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02671903
- Acronym / sponsor ID
- HOPE-HF / 15HH2828
- Conditions
- Heart Failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- British Heart Foundation, Medtronic
- Study start
- Jan 2016 (actual)
- Primary completion
- 31 Oct 2020 (actual)
- Study completion
- 31 Oct 2020 (actual)
- First posted
- 2 Feb 2016 (estimated)
- Results
- Posted 4 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pacemaker: AV optimised, His pacing | Active comparator | Device: Pacemaker: AV optimised, His pacing.Subjects will remain in this arm for 6 months before being crossed-over. See below intervention details. |
| No pacing | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Device | Pacemaker: AV optimised, His pacing |
Primary outcome
Changes in Exercise Capacity.
Time frame: Baseline, 6 months and 12 months post randomisation.
Measured using peak oxygen uptake (VO2).
11 secondary outcomes
Changes in Echocardiographic Measurement of Left Ventricular Function (Ejection Fraction)
Time frame: 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.
Changes in Quality of Life Scores. - Minnesota
Time frame: Baseline, 6 months and 12 months post randomisation.
Cost Effectiveness Analysis (Using a Custom Designed Resource Utilisation Questionnaire)
Time frame: Baseline.
Changes in Percentage Pacing
Time frame: Baseline, 6 months and 12 months post randomisation.
Changes in Arrythmia Burden (%).
Time frame: Baseline, 6 months and 12 months post randomisation.
Changes in Pacing Thresholds (Volts).
Time frame: Baseline, 6 months and 12 months post randomisation.
Changes in R Wave Amplitude.
Time frame: Baseline, 6 months and 12 months post randomisation.
Changes in Lead Impedance (Ohms).
Time frame: Baseline, 6 months and 12 months post randomisation.
Fluoroscopy Time During Device Insertion.
Time frame: Taken at Device Insertion Visit (2). Baseline measure.
Changes in Quality of Life Scores. - EQ5D Health State Score
Time frame: Baseline, 6 months and 12 months post randomisation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zachary Whinnett, BMBS MRCP principal investigator
Senior Lecturer, Consultant Cardiologist and Electrophysiologist
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pacemaker: AV optimised, His pacing. in people with Heart Failure, run by Imperial College London at 15 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Exercise Capacity. (time frame: Baseline, 6 months and 12 months post randomisation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.