Cardiomyopathy, HypertrophicNCT03450252
Pacemaker Therapy for Drug-refractory Symptoms in Mid-cavity Hypertrophic Cardiomyopathy
A study testing Active pacing and Back-up pacing in people with Cardiomyopathy, Hypertrophic, run by Barts & The London NHS Trust at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiomyopathy, Hypertrophic
- What is being tested?
- Active pacing and Back-up pacing
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Feb 2018to 20 Jan 2023
- Phase
- Interventional
- 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
- Male or female, >18 years.
- Referred for PPM +/- ICD implantation for either primary prevention of sudden cardiac death or other indications such as heart block or obstructive physiology.
- HCM patients with evidence of mid-cavity gradient demonstrated by echocardiography and gradient ≥30 mmHg confirmed by cardiac catheterisation at rest or with isoprenaline provocation.
- All patients should be taking maximum tolerated doses of beta blockers or verapamil with or without disopyramide.
- Symptoms refractory to optimum medical therapy as above, for example breathlessness, chest pain, dizziness, or syncope.
Who cannot join
- Patients with multi-level obstruction, i.e. across the mid-cavity and outflow tract.
- Patients with moderate or severe valvular stenosis or regurgitation.
- Patients with a history of myocardial infarction or acute coronary syndrome.
- Patients unable to provide informed consent.
- Patients in atrial fibrillation.
- Pregnancy.
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- Renal failure.
- If considered unsuitable by clinician.
- Patients already participating in trials involving invasive procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Distal Ventricular Pacing and Intraventricular Gradient Reduction for Symptomatic Relief in Drug Refractory Hypertrophic Cardiomyopathy Patients With Mid-cavity Obstruction
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.
Read the 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?
- Conditions
- Cardiomyopathy, Hypertrophic
- Being tested
- Active pacing, Back-up pacing
- Keywords
- HCM, Mid-cavity, Pacing
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active pacingDevice
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.
Back-up pacingDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active pacing | Experimental | Active ventricular pacing. The pacemaker is set-up with a short atrio-ventricular delay to allow for appropriate pacing capture of the ventricle. Receives: Device: Active pacing |
| Back-up pacing | Sham comparator | 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. Receives: Device: Back-up pacing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive gradient (mmHg)
Acute invasively defined gradient change in mmHg across the mid-cavity with optimal ventricular pacing setting
Measured: Measured during pacemaker implant. Pressure gradients will be measured at different pacing sites during the implant.
Secondary outcomes (6)
Symptomatic assessment via SF36 questionnaire
Generalised health related questionnaire
Measured: Pre-implant, 4 months, and 8 months
Symptomatic assessment via Kansas City Cardiomyopathy questionnaire
Cardiomyopathy health related questionnaire
Measured: Pre-implant, 4 months, and 8 months
Symptomatic assessment via calculation of New York Heart Association (NYHA) functional class
Classification of extent of heart failure
Measured: Pre-implant, 4 months, and 8 months
Exercise performance assessed by 6 minute walk test (6MWT)
Sub-maximal exercise test
Measured: Pre-implant, 4 months, and 8 months
Exercise performance assessed by Cardiopulmonary exercise testing (CPET) stress echocardiography.
Maximal exercise test with simultaneous echocardiography
Measured: Pre-implant, 4 months, and 8 months
Levels of Brain Natriuretic Peptide
Protein associated with heart failure
Measured: Pre-implant, 4 months, and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start9 Feb 2018
- Primary completion20 Jan 2023
- Study completion20 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiomyopathy, HypertrophicStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 four and eight 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 four 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 four month period, participants will undergo repeat assessment as above. That will conclude the study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saidi A Mohiddin, BSc, MBChB, FRCP, MD, Principal investigator, Barts Health NHS Trust and Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03450252
- Sponsor's protocol ID
- V11_27 10 20
- Status last verified
- Feb 2023
- First submitted
- 17 Jan 2018
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Malcolmson JW, Hughes RK, Husselbury T, Khan K, Learoyd AE, Lees M, Wicks EC, Smith J, Simms AD, Moon JC, Lopes LR, O'Mahony C, Sekhri N, Elliott PM, Petersen SE, Dhinoja MB, Mohiddin SA. Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing. Circ Arrhythm Electrophysiol. 2024 Jul;17(7):e012570. doi: 10.1161/CIRCEP.123.012570. Epub 2024 Jun 19.
PubMed 39012930
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Distal Ventricular Pacing and Intraventricular Gradient Reduction for Symptomatic Relief in Drug Refractory Hypertrophic Cardiomyopathy Patients With Mid-cavity Obstruction
- ClinicalTrials.gov ID
- NCT03450252
- Acronym / sponsor ID
- V11_27 10 20
- Conditions
- Cardiomyopathy, Hypertrophic
- Keywords
- HCM, Mid-cavity, Pacing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Study start
- 9 Feb 2018 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 20 Jan 2023 (actual)
- First posted
- 1 Mar 2018 (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 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.
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?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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 four and eight 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 four 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 four month period, participants will undergo repeat assessment as above. That will conclude the study.
| Arm | Type | Receives |
|---|---|---|
| Active pacing | Experimental | Device: Active pacingActive ventricular pacing. The pacemaker is set-up with a short atrio-ventricular delay to allow for appropriate pacing capture of the ventricle. |
| Back-up pacing | Sham comparator | Device: Back-up pacingBack-up pacing. The pacemaker is set-up to sense and pace only in the right atrium (AAI) without any pacing capacity in the ventricle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female, >18 years.
- Referred for PPM +/- ICD implantation for either primary prevention of sudden cardiac death or other indications such as heart block or obstructive physiology.
- HCM patients with evidence of mid-cavity gradient demonstrated by echocardiography and gradient ≥30 mmHg confirmed by cardiac catheterisation at rest or with isoprenaline provocation.
- All patients should be taking maximum tolerated doses of beta blockers or verapamil with or without disopyramide.
- Symptoms refractory to optimum medical therapy as above, for example breathlessness, chest pain, dizziness, or syncope.
Key exclusion criteria (9 listed)
- Patients with multi-level obstruction, i.e. across the mid-cavity and outflow tract.
- Patients with moderate or severe valvular stenosis or regurgitation.
- Patients with a history of myocardial infarction or acute coronary syndrome.
- Patients unable to provide informed consent.
- Patients in atrial fibrillation.
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 |
|---|---|---|
| Active pacingVentricular 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. | Device | Active pacing |
| Back-up pacingBack-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 |
Primary outcome
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
6 secondary outcomes
Symptomatic assessment via SF36 questionnaire
Time frame: Pre-implant, 4 months, and 8 months
Symptomatic assessment via Kansas City Cardiomyopathy questionnaire
Time frame: Pre-implant, 4 months, and 8 months
Symptomatic assessment via calculation of New York Heart Association (NYHA) functional class
Time frame: Pre-implant, 4 months, and 8 months
Exercise performance assessed by 6 minute walk test (6MWT)
Time frame: Pre-implant, 4 months, and 8 months
Exercise performance assessed by Cardiopulmonary exercise testing (CPET) stress echocardiography.
Time frame: Pre-implant, 4 months, and 8 months
Levels of Brain Natriuretic Peptide
Time frame: Pre-implant, 4 months, and 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
- Derived from this study: PubMed 39012930Malcolmson JW, Hughes RK, Husselbury T, Khan K, Learoyd AE, Lees M, Wicks EC, Smith J, Simms AD, Moon JC, Lopes LR, O'Mahony C, Sekhri N, Elliott PM, Petersen SE, Dhinoja MB, Mohiddin SA. Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing. Circ Arrhythm Electrophysiol. 2024 Jul;17(7):e012570. doi: 10.1161/CIRCEP.123.012570. Epub 2024 Jun 19.
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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.
Saidi A Mohiddin, BSc, MBChB, FRCP, MD principal investigator
Barts Health NHS Trust and Queen Mary University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active pacing and Back-up pacing in people with Cardiomyopathy, Hypertrophic, run by Barts & The London NHS Trust 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 5 inclusion and 9 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 1 Feb 2023. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Invasive gradient (mmHg) (time frame: Measured during pacemaker implant. Pressure gradients will be measured at different pacing sites during the implant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03450252, which also lists 1 linked publication.
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 1 Feb 2023.