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Pacemaker Therapy for Drug-refractory Symptoms in Mid-cavity Hypertrophic Cardiomyopathy

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ClinicalTrials.gov Identifier: NCT03450252
Recruitment Status : Recruiting
First Posted : March 1, 2018
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Barts & The London NHS Trust

Brief Summary:
The main aim of this study is to assess the acute effects of a pacemaker on reducing abnormally high intracavity pressures in the hearts of patients with mid-cavity obstructive hypertrophic cardiomyopathy (HCM). During a 12-month period of double-blinded follow-up, descriptive data will be collected on patients symptomatic and physical performance during dichotomous pacemaker settings for 6-months each (active and back-up). The statistical information collected will be used to design a much larger research trial of patient benefit.

Condition or disease Intervention/treatment Phase
Cardiomyopathy, Hypertrophic Device: Active pacing Device: Back-up pacing Not Applicable

Detailed Description:

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, affecting 1 in 500 of the general population. It is characterised by abnormal thickening of the heart muscle. The various patterns of thickening of the muscle in the main pumping chamber, or left ventricle (LV), can result in obstruction to blood flow within the heart, raising the pressures in the heart and placing extra strain on the heart muscle.

The obstruction can cause patients to suffer from symptoms such as shortness of breath and chest pain, along with poor exercise tolerance, and dizzy spells. In very symptomatic patients with the commonest type of obstruction, invasive procedures performed either via an open-heart or keyhole operation can reduce the increased basal septal muscle mass at the point of obstruction. However, in around 1 in 10 HCM patients, the obstruction is deep within the LV where a ring of thick muscle blocks blood flow when it contracts. These patients provide a challenge for doctors, as this type of obstruction is much less suitable for open heart or keyhole operation.

An alternative is to use a cardiac pacemaker to alter the timing of the contraction in the ring of thick muscle such that different parts of the ring contract at different times and thereby reduce obstruction to blood flow. The investigators' early experience with this new treatment shows that carefully placing the pacemaker wires can reduce the obstruction and improve patient symptoms.

Key questions of this research include:

  • How much can optimal ventricular pacing reduce the obstruction by?
  • How important is choosing which part of the heart the pacemaker activates first?
  • Does reducing obstruction in this way make patients better in the short and long term?

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Taking part in this study will involve recording the information at a pre-implant visit, a visit for cardiac pacemaker implantation and follow-up visits six and twelve months later.

At the pre-implant visit, participants will undergo assessment of symptoms, physical performance and blood test for a protein, Brain natriuretic peptide (BNP).

During the pacemaker implantation, the investigators will record the pressures within the heart using a catheter during both active pacing and back-up pacing settings.

The day after the pacemaker implant participants will undergo double-blind randomisation into either the treatment or non-treatment arm (active or back-up pacing respectively). At six months, cross-over takes place with assessment as above, before device reprogramming into either the treatment or non-treatment arm depending on which was completed first.

At the end of the second six month period, participants will undergo repeat assessment as above. That will conclude the study.

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Distal Ventricular Pacing and Intraventricular Gradient Reduction for Symptomatic Relief in Drug Refractory Hypertrophic Cardiomyopathy Patients With Mid-cavity Obstruction
Actual Study Start Date : February 9, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Active pacing
Active ventricular pacing. The pacemaker is set-up with a short atrio-ventricular delay to allow for appropriate pacing capture of the ventricle.
Device: Active pacing
Ventricular pacing via the invasive haemodynamic study-defined optimal pacing site in order to relieve pressure gradient across the mid-cavity obstruction in mid-cavity obstructive variant hypertrophic cardiomyopathy.

Sham Comparator: Back-up pacing
Back-up pacing. The pacemaker is set-up to sense and pace only in the right atrium (AAI) without any pacing capacity in the ventricle.
Device: Back-up pacing
Back-up pacing. The pacemaker is set-up to sense and pace only in the right atrium (AAI) without any pacing capacity in the ventricle.




Primary Outcome Measures :
  1. Invasive gradient (mmHg) [ Time Frame: Measured during pacemaker implant. Pressure gradients will be measured at different pacing sites during the implant. ]
    Acute invasively defined gradient change in mmHg across the mid-cavity with optimal ventricular pacing setting


Secondary Outcome Measures :
  1. Symptomatic assessment via SF36 questionnaire [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Generalised health related questionnaire

  2. Symptomatic assessment via Kansas City Cardiomyopathy questionnaire [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Cardiomyopathy health related questionnaire

  3. Symptomatic assessment via calculation of New York Heart Association (NYHA) functional class [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Classification of extent of heart failure

  4. Exercise performance assessed by 6 minute walk test (6MWT) [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Sub-maximal exercise test

  5. Exercise performance assessed by Cardiopulmonary exercise testing (CPET) stress echocardiography. [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Maximal exercise test with simultaneous echocardiography

  6. Levels of Brain Natriuretic Peptide [ Time Frame: Pre-implant, 6 months, and 1 year. ]
    Protein associated with heart failure



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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:

  1. Male or female, >18 years.
  2. Referred for PPM +/- ICD implantation for either primary prevention of sudden cardiac death or other indications such as heart block or obstructive physiology.
  3. HCM patients with a mid-cavity gradient of ≥30 mmHg demonstrated by echocardiography and gradient confirmed by cardiac catheterisation at rest or with isoprenaline provocation. HCM morphology confirmed by cardiac MRI.
  4. All patients should be taking maximum tolerated doses of beta blockers or verapamil with or without disopyramide.
  5. Symptoms refractory to optimum medical therapy as above, for example breathlessness, chest pain, dizziness, or syncope.

Exclusion Criteria:

  1. Patients with multi-level obstruction, i.e. across the mid-cavity and outflow tract.
  2. Patients with moderate or severe valvular stenosis or regurgitation.
  3. Patients with a history of myocardial infarction or acute coronary syndrome.
  4. Patients unable to provide informed consent.
  5. Patients in atrial fibrillation.
  6. Pregnancy.
  7. Renal failure.
  8. If considered unsuitable by clinician.
  9. Patients already participating in trials involving invasive procedures.

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): NCT03450252


Contacts
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Contact: Saidi A Mohiddin, BSc, MBChB, FRCP, MD 020 7377 7000 saidi.mohiddin@bartshealth.nhs.uk
Contact: James W Malcolmson, BSc 020 7377 7000 ext 57040 james.malcolmson@bartshealth.nhs.uk

Locations
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United Kingdom
Barts Heart Centre Recruiting
London, Thames, United Kingdom, EC1A 7BE
Contact: Saidi A Mohiddin    020 7377 7000    saidi.mohiddin@bartshealth.nhs.uk   
Contact: James W Malcolmson, BSc    020 7377 7000 ext 57040    james.malcolmson@bartshealth.nhs.uk   
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
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Principal Investigator: Saidi A Mohiddin, BSc, MBChB, FRCP, MD Barts Health NHS Trust and Queen Mary University of London

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Responsible Party: Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT03450252     History of Changes
Other Study ID Numbers: V9_09 11 17
First Posted: March 1, 2018    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Barts & The London NHS Trust:
HCM
Mid-cavity
Pacing
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases