Heart Failure, SystolicPhase 2/3OPT-cont 2NCT04201015
Optimising Pacing for Contractility 2
A Phase 2/3 study testing Heart rate optimisation using force frequency data in people with Heart Failure, Systolic and Pacemaker, run by University of Leeds at 1 site in United Kingdom.
Trial summary
The investigators have demonstrated that they can reliably identify an optimum heart rate range for contractility of the left ventricle in patients with chronic heart failure (CHF). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic, Pacemaker
- What is being tested?
- Heart rate optimisation using force frequency data
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jun 2020to 31 Mar 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Clinical, echocardiographic and neurohormonal evidence of heart failure
- Cardiac pacemaker,
- Able to perform a peak exercise test,
- Willing and able to give informed consent.
Who cannot join
- Angina pectoris symptoms limiting exercise tolerance,
- Unstable heart failure symptoms (medical therapy changes in last three months), Poor image quality,
- Calcium channel blockers (CCBs).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Leeds General Infirmary
Leeds
Klaus K Witte, MD, k.k.witte@leeds.ac.uk
Klaus K Witte, MD
About this study
Official title: Mechanisms, Safety and Efficacy of Optimising Pacemaker Heart Rate for Contractility: Effects on Walk Time, Cardiac Remodelling and Quality of Life
The investigators have demonstrated that they can reliably identify an optimum heart rate range for contractility of the left ventricle in patients with chronic heart failure (CHF). They have also demonstrated in an acute cross-over and a small parallel group feasibility study that keeping the heart rate in this range (versus standard rate-response programming) in patients with CHF is associated with increased exercise time on a treadmill (around 60s or 10%). They now want to explore in a randomised, placebo-controlled 3-arm parallel group trial whether optimal programming versus standard rate-response programming versus no rate-response programming for 6 months leads to appreciable improvements in exercise time and quality of life, while having no adverse effects on left ventricular function and battery longevity and what the mechanisms of this might be.
450 patients with CHF and a pacemaker will undergo the non-invasive echocardiographic assessment to establish the force frequency relationship and the optimal heart rate for contractility. They will then perform a treadmill walk test, complete quality of life questionnaires and be offered the opportunity to participate in a series of mechanistic substudies. They will then be randomised to optimal rate-response settings, standard rate response settings or no rate-response settings and followed up at 6 months at which point the tests will be repeated.
Read the detailed description
Detailed Description:
Design: This will be a randomised, double-blind 'placebo' controlled trial of optimised programming versus standard rate-response settings, aiming to determine whether the short term improvements translate into longer term benefits.
Study participants: 450 adult patients (>18years).
Study Procedures: Patients attending the heart failure clinic, the pacemaker clinic or previous research participants will be approached with a standard letter and information sheet and then a telephone call to make sure any remaining questions are answered.
Patients agreeing to participate will attend the clinical research facility (CRF) and will be asked to sign a consent form. Each patient will have a standard device check, check of their demographic data, and co-morbidities. The investigators will record a resting cardiac ultrasound, and measure the force frequency relationship (FFR) to determine critical heart rate (HR), and the optimal range of HR rise. All images will be stored for offline analysis. Participants will then be asked to do a symptom-limited walk test on the treadmill (until they cannot do any more). At this first visit, participants will also complete quality of life questionnaires and be invited to participate in substudies including cardiac magnetic resonance, blood tests, tests of autonomic dysfunction. All of these activities will take place in the Clinical Research Facility at Leeds General Infirmary.
Randomisation: Each patient will then be randomised to either optimised programming (n=225) as predicted by their force-frequency curve (n=200), standard settings (n=112) or no rate response programming (n=113). In the optimised group, programming will keep heart rates below the critical HR. Randomisation will be by a random number generator and programming will be undertaken by one of my colleagues to maintain blinding.
Follow-up: Each patient will be called at one month to check that they are tolerating any changes and will then be invited back at 6 months for a repeat resting echocardiogram, treadmill walk test and quality of life assessment.
Data: All data will be stored on a bespoke Excel spreadsheet on an LTHT server in a password-protected folder.
Primary Endpoint: The effects of heart rate programming that optimises heart rate for contractility on change in treadmill-based walk distance over six months in patients with heart failure and a pacemaker.
Secondary endpoints: 1) the safety of pacemaker programming optimised for heart rate in patients with heart failure and a pacemaker, 2) the effect of this programming on change of quality of life at 6 months 3) the effect of this programming on change in cardiac function at 6 months.
Mechanistic endpoints: 1) The effect of heart rate programming on measures of autonomic function, 2) Changes in cardiac function during exercise, 3) The effect of optimised heart rate programming on strain, wall stress and perfusion by cardiac magnetic resonance, 4) changes in biomarkers associated with heart failure
- Conditions
- Heart Failure, Systolic, Pacemaker
- Being tested
- Heart rate optimisation using force frequency data
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heart rate optimisation using force frequency dataDevice
Programming heart rate rise according to the force frequency relationship
| Study group | Role | What they receive |
|---|---|---|
| Standard rate-response settings | No intervention | Patients allocated to standard rate-response settings. |
| Rate-response settings off | Active comparator | Patients allocated to deactivated rate-response settings. Receives: Device: Heart rate optimisation using force frequency data |
| Optimized rate-response settings | Experimental | Patients allocated to optimised rate-response settings. Receives: Device: Heart rate optimisation using force frequency data |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treadmill walk time
Time walked during a standard incremental treadmill test
Measured: 6 months
Secondary outcomes (7)
Quality of life 1
EQ5D-5L score
Measured: 6 months
Quality of life 2
KCCQ score
Measured: 6 months
Clinical composite score
Clinical outcomes combined (death, hospitalisation, NYHA symptom level, diuretic dose
Measured: 6 months
Cardiac function during exercise measured by LVEF on echocardiogrpahy
As assessed on a cycle ergometer
Measured: 6 months
Wall stress by cardiac MRI
Wall stress assessed by cardiac MRI
Measured: 6 months
Autonomic dysfunction
Measures of Muscle Sympathetic Nerve Activity
Measured: 6 months
Autonomic dysfunction
Heart rate variability
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start1 Jun 2020
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Klaus K Witte, MD, University of Leeds
- Investigators
- John Gierula, PhD, Principal investigator, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04201015
- Sponsor's protocol ID
- 277578
- Acronym
- OPT-cont 2
- Status last verified
- Sep 2024
- First submitted
- 11 Dec 2019
- Last updated
- 26 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: An application with appropriate ethical approval is made to the corresponding author and the deidentified data would be transferred securely to servers of the applicant's organisation.
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms, Safety and Efficacy of Optimising Pacemaker Heart Rate for Contractility: Effects on Walk Time, Cardiac Remodelling and Quality of Life
- ClinicalTrials.gov ID
- NCT04201015
- Acronym / sponsor ID
- OPT-cont 2 / 277578
- Conditions
- Heart Failure, Systolic, Pacemaker
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 16 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators have demonstrated that they can reliably identify an optimum heart rate range for contractility of the left ventricle in patients with chronic heart failure (CHF). They have also demonstrated in an acute cross-over and a small parallel group feasibility study that keeping the heart rate in this range (versus standard rate-response programming) in patients with CHF is associated with increased exercise time on a treadmill (around 60s or 10%). They now want to explore in a randomised, placebo-controlled 3-arm parallel group trial whether optimal programming versus standard rate-response programming versus no rate-response programming for 6 months leads to appreciable improvements in exercise time and quality of life, while having no adverse effects on left ventricular function and battery longevity and what the mechanisms of this might be.
450 patients with CHF and a pacemaker will undergo the non-invasive echocardiographic assessment to establish the force frequency relationship and the optimal heart rate for contractility. They will then perform a treadmill walk test, complete quality of life questionnaires and be offered the opportunity to participate in a series of mechanistic substudies. They will then be randomised to optimal rate-response settings, standard rate response settings or no rate-response settings and followed up at 6 months at which point the tests will be repeated.
Detailed description
Detailed Description:
Design: This will be a randomised, double-blind 'placebo' controlled trial of optimised programming versus standard rate-response settings, aiming to determine whether the short term improvements translate into longer term benefits.
Study participants: 450 adult patients (>18years).
Study Procedures: Patients attending the heart failure clinic, the pacemaker clinic or previous research participants will be approached with a standard letter and information sheet and then a telephone call to make sure any remaining questions are answered.
Patients agreeing to participate will attend the clinical research facility (CRF) and will be asked to sign a consent form. Each patient will have a standard device check, check of their demographic data, and co-morbidities. The investigators will record a resting cardiac ultrasound, and measure the force frequency relationship (FFR) to determine critical heart rate (HR), and the optimal range of HR rise. All images will be stored for offline analysis. Participants will then be asked to do a symptom-limited walk test on the treadmill (until they cannot do any more). At this first visit, participants will also complete quality of life questionnaires and be invited to participate in substudies including cardiac magnetic resonance, blood tests, tests of autonomic dysfunction. All of these activities will take place in the Clinical Research Facility at Leeds General Infirmary.
Randomisation: Each patient will then be randomised to either optimised programming (n=225) as predicted by their force-frequency curve (n=200), standard settings (n=112) or no rate response programming (n=113). In the optimised group, programming will keep heart rates below the critical HR. Randomisation will be by a random number generator and programming will be undertaken by one of my colleagues to maintain blinding.
Follow-up: Each patient will be called at one month to check that they are tolerating any changes and will then be invited back at 6 months for a repeat resting echocardiogram, treadmill walk test and quality of life assessment.
Data: All data will be stored on a bespoke Excel spreadsheet on an LTHT server in a password-protected folder.
Primary Endpoint: The effects of heart rate programming that optimises heart rate for contractility on change in treadmill-based walk distance over six months in patients with heart failure and a pacemaker.
Secondary endpoints: 1) the safety of pacemaker programming optimised for heart rate in patients with heart failure and a pacemaker, 2) the effect of this programming on change of quality of life at 6 months 3) the effect of this programming on change in cardiac function at 6 months.
Mechanistic endpoints: 1) The effect of heart rate programming on measures of autonomic function, 2) Changes in cardiac function during exercise, 3) The effect of optimised heart rate programming on strain, wall stress and perfusion by cardiac magnetic resonance, 4) changes in biomarkers associated with heart failure
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard rate-response settings | No intervention | –Patients allocated to standard rate-response settings. |
| Rate-response settings off | Active comparator | Device: Heart rate optimisation using force frequency dataPatients allocated to deactivated rate-response settings. |
| Optimized rate-response settings | Experimental | Device: Heart rate optimisation using force frequency dataPatients allocated to optimised rate-response settings. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical, echocardiographic and neurohormonal evidence of heart failure
- Cardiac pacemaker,
- Able to perform a peak exercise test,
- Willing and able to give informed consent.
Key exclusion criteria (3 listed)
- Angina pectoris symptoms limiting exercise tolerance,
- Unstable heart failure symptoms (medical therapy changes in last three months), Poor image quality,
- Calcium channel blockers (CCBs).
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 |
|---|---|---|
| Heart rate optimisation using force frequency dataProgramming heart rate rise according to the force frequency relationship | Device | Optimized rate-response settings, Rate-response settings off |
Primary outcome
Treadmill walk time
Time frame: 6 months
Time walked during a standard incremental treadmill test
7 secondary outcomes
Quality of life 1
Time frame: 6 months
Quality of life 2
Time frame: 6 months
Clinical composite score
Time frame: 6 months
Cardiac function during exercise measured by LVEF on echocardiogrpahy
Time frame: 6 months
Wall stress by cardiac MRI
Time frame: 6 months
Autonomic dysfunction
Time frame: 6 months
Autonomic dysfunction
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2024.
- Individual participant dataSharing planned: Yes. An application with appropriate ethical approval is made to the corresponding author and the deidentified data would be transferred securely to servers of the applicant's organisation.
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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.
John Gierula, PhD principal investigator
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Heart rate optimisation using force frequency data in people with Heart Failure, Systolic and Pacemaker, run by University of Leeds at 1 site 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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Klaus K Witte, MD (01133926642, k.k.witte@leeds.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treadmill walk time (time frame: 6 months). 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 26 Sep 2024.