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Optimising Pacing for Contractility 2 (OPT-cont 2)

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ClinicalTrials.gov Identifier: NCT04201015
Recruitment Status : Recruiting
First Posted : December 16, 2019
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
KK Witte, University of Leeds

Brief 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). 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.

360 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.


Condition or disease Intervention/treatment Phase
Heart Failure, Systolic Pacemaker Device: Heart rate optimisation using force frequency data Phase 2 Phase 3

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: 360 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=120) as predicted by their force-frequency curve, standard settings (n=120) or no rate response programming (n=120). 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Only the technician doing the programming will know how the pacemaker has been set.
Primary Purpose: Treatment
Official Title: Mechanisms, Safety and Efficacy of Optimising Pacemaker Heart Rate for Contractility: Effects on Walk Time, Cardiac Remodelling and Quality of Life
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

Arm Intervention/treatment
No Intervention: Standard rate-response settings
Patients allocated to standard rate-response settings.
Active Comparator: Rate-response settings off
Patients allocated to deactivated rate-response settings.
Device: Heart rate optimisation using force frequency data
Programming heart rate rise according to the force frequency relationship

Experimental: Optimized rate-response settings
Patients allocated to optimised rate-response settings.
Device: Heart rate optimisation using force frequency data
Programming heart rate rise according to the force frequency relationship




Primary Outcome Measures :
  1. Treadmill walk time [ Time Frame: 6 months ]
    Time walked during a standard incremental treadmill test


Secondary Outcome Measures :
  1. Quality of life 1 [ Time Frame: 6 months ]
    EQ5D-5L score

  2. Quality of life 2 [ Time Frame: 6 months ]
    KCCQ score

  3. Clinical composite score [ Time Frame: 6 months ]
    Clinical outcomes combined (death, hospitalisation, NYHA symptom level, diuretic dose

  4. Cardiac function during exercise measured by LVEF on echocardiogrpahy [ Time Frame: 6 months ]
    As assessed on a cycle ergometer

  5. Wall stress by cardiac MRI [ Time Frame: 6 months ]
    Wall stress assessed by cardiac MRI

  6. Autonomic dysfunction [ Time Frame: 6 months ]
    Measures of Muscle Sympathetic Nerve Activity

  7. Autonomic dysfunction [ Time Frame: 6 months ]
    Heart rate variability



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Left ventricular systolic dysfunction (LVEF<50%),
  • Cardiac pacemaker,
  • Able to perform a peak exercise test,
  • Willing and able to give informed consent.

Exclusion Criteria:

  • Angina pectoris symptoms limiting exercise tolerance,
  • Unstable heart failure symptoms (medical therapy changes in last three months), Poor image quality,
  • Calcium channel blockers (CCBs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04201015


Contacts
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Contact: Klaus K Witte, MD 01133926642 k.k.witte@leeds.ac.uk

Locations
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United Kingdom
Leeds General Infirmary Recruiting
Leeds, United Kingdom
Contact: Klaus K Witte, MD       k.k.witte@leeds.ac.uk   
Principal Investigator: Klaus K Witte, MD         
Sponsors and Collaborators
University of Leeds
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Responsible Party: KK Witte, Prinicipal Investigator, University of Leeds
ClinicalTrials.gov Identifier: NCT04201015    
Other Study ID Numbers: 277578
First Posted: December 16, 2019    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: after initial analysis

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure, Systolic
Heart Failure
Heart Diseases
Cardiovascular Diseases