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Recruiting NCT04201015

Optimising Pacing for Contractility 2

Phase II / Phase III Interventional Heart Failure, Systolic Pacemaker

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Heart rate optimisation using force frequency data.
Who it may be relevant to
Registry conditions: Heart Failure, Systolic, Pacemaker. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Mechanisms, Safety and Efficacy of Optimising Pacemaker Heart Rate for Contractility: Effects on Walk Time, Cardiac Remodelling and Quality of Life

Overview

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

Interventions

  • Device Heart rate optimisation using force frequency data
    Programming heart rate rise according to the force frequency relationship

Primary outcome measures

  • Treadmill walk time [Time frame: 6 months]
Secondary outcome measures (7)
  • 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]

Eligibility criteria

Inclusion criteria

  • Clinical, echocardiographic and neurohormonal evidence of heart failure
  • 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

United Kingdom · 1 center
  • Leeds General Infirmary — Leeds

Identifiers

NCT: NCT04201015 · 277578

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗