Hypertrophic CardiomyopathyPINCHcmNCT04231032
Paced Dyssynchrony and Myocardial Perfusion IN apiCal Hcm
A study testing Asynchronous dual chamber pacing (DOO) with paced ventricular activation and Asynchronous atrial pacing (AOO) with intrinsic ventricular activation in people with Hypertrophic Cardiomyopathy, run by Barts & The London NHS Trust at 1 site in United Kingdom.
Trial summary
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. A relatively common subgroup of HCM patients have apical HCM - a type of heart muscle disease that causes abnormal muscle thickening towards the tip (apex) of the heart. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertrophic Cardiomyopathy
- What is being tested?
- Asynchronous dual chamber pacing (DOO) with paced ventricular activation and Asynchronous atrial pacing (AOO) with intrinsic ventricular activation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Jun 2021to 20 Feb 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.
- HCM patients with apical HCM defined as apical hypertrophy with apical LV systolic obliteration and the presence of characteristic ECG changes. Participants with a mixed cardiac phenotype will be considered if they also meet these criteria and do not have resting outflow tract obstruction.
- A programmable intracardiac pacing device with a right atrial lead and an apically / low septal located right ventricular lead.
- Willing and able to provide informed consent.
Who cannot join
- Outflow tract obstruction >50 mmHg at rest due to systolic anterior mitral movement.
- Evidence of high-grade heart block.
- Moderate or severe primary valvular disease.
- Unrevascularised, known, significant coronary disease: the significance of any known coronary disease will be determined after discussion with an independent clinician.
- Atrial fibrillation at the time of randomisation.
- Inability to undergo CMR with adenosine stress and gadolinium contrast imaging.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
About this study
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. A relatively common subgroup of HCM patients have apical HCM - a type of heart muscle disease that causes abnormal muscle thickening towards the tip (apex) of the heart. This can impair the heart's own blood flow through the thickened heart muscle. We think this is one of the causes for symptoms such as shortness of breath and chest pain. If medications are ineffective at treating symptoms, there are few further options available, limited to invasive heart surgery.
This study aims to determine if it is possible to improve the blood flow within by altering the settings of patients' permanent pacemakers, dynamic microvascular obstruction is an important cause of perfusion abnormalities in HCM and whether introducing localized dyssynchrony with ventricular pacing improves this. This phased study will include patients with apical HCM that already have implanted pacemaker devices to remove risks associated with device implantation.
The study may provide insights into novel mechanisms for symptoms in HCM and provide new methods for treating a patient group in whom therapeutic options can be extremely limited.
Read the detailed description
The treatments for people with apical HCM and symptoms are limited but include medicines. The use of a pacemaker in this situation is an experimental treatment which has not yet been fully explored. We believe symptoms are linked with abnormalities in blood flow through the heart muscle at the tip / apex of the heart and wish to see if using a pacemaker can improve such abnormalities. We want to test if this treatment works using a clinical trial to help us decide whether this is a viable treatment option that may be offered to other patients with the condition. The null hypothesis states that there will be no difference in blood flow through the heart muscle with pacing. The alternative hypothesis states that there will be a significant difference in blood flow through the heart muscle with pacing. This was chosen based upon our current knowledge that abnormal blood flow in the heart muscle in apical HCM is linked with abnormal squeeze at the apex / tip and symptoms. Echocardiography pilot data has demonstrated a reduction in squeeze at the apex of the heart when using the pacemaker to cause the heart muscle to contract in a different way.
Our alternative hypothesis therefore is that we can use the pacemaker to reduce squeeze at the apex and improve blood flow through the heart muscle. This is a single centre, prospective pilot study. Because data on acute changes in perfusion with pacing in apical HCM are extremely limited, the most ethical methodology is to perform a two-phase study. Phase A of the study assesses acute changes in blood flow through the heart muscle during different pacemaker settings (active and back-up), looking for potential efficacy of the intervention. Secondary outcomes of Phase A include recruitment rate and proportion of patients willing to proceed to Phase B. Phase B of the study consists of entering those same patients into a randomised double-blind cross-over 6-month follow-up pilot to collect baseline statistical data and assess acceptability of study protocol to design a future study. Here, assessment of further secondary outcomes will allow establishment of baseline statistical data for the design of an outcomes-based clinical trial. Patients will only be entered into phase B of the study if an improvement is seen in myocardial perfusion with pacing during phase A.
- Conditions
- Hypertrophic Cardiomyopathy
- Being tested
- Asynchronous dual chamber pacing (DOO) with paced ventricular activation, Asynchronous atrial pacing (AOO) with intrinsic ventricular activation
- Keywords
- Apical hypertrophic cardiomyopathy, Pacemaker, Perfusion
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Apical Hypertrophic Cardiomyopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asynchronous dual chamber pacing (DOO) with paced ventricular activationOther
Alteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation).
Asynchronous atrial pacing (AOO) with intrinsic ventricular activationOther
Alteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation).
| Study group | Role | What they receive |
|---|---|---|
| Active ventricular pacing | Active comparator | Asynchronous dual chamber pacing (DOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm) Receives: Other: Asynchronous dual chamber pacing (DOO) with paced ventricular activation |
| Back-up ventricular pacing | Placebo comparator | Asynchronous atrial pacing with intrinsic ventricular activation (AOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm) Receives: Other: Asynchronous atrial pacing (AOO) with intrinsic ventricular activation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial perfusion mapping
Percentage change in regional myocardial perfusion between baseline and pacing measured using myocardial blood flow (MBF) mapping at Cardiovascular Magnetic Resonance (CMR) imaging.
Measured: Acute changes during the CMR scan on Visit 1 (day 1)
Secondary outcomes (13)
Proportion successfully completing the CMR scan with interpretable images.
Number of participants whose perfusion imaging is readable
Measured: After all visit 1 completed (within 6 months)
Myocardial contractility via CMR
Alterations in regional and global myocardial contractility and relaxation measured by cardiac magnetic resonance imaging.
Measured: Acute changes during the CMR scan on Visit 1 (day 1)
Myocardial contractility via echocardiography
Alterations in regional and global myocardial contractility and relaxation measured by echocardiography.
Measured: Acute changes during the echocardiogram scan on Visit 1 (day 1)
Proportion unwilling to proceed to Phase B.
Proportion of participants who are unwilling to proceed to Phase B.
Measured: After all visit 1 completed (within 6 months).
Recruitment rate.
The rate at which participants are recruited into the study.
Measured: 12 months.
Exercise performance on Bruce protocol treadmill exercise tolerance test (ETT)
Time in minutes on the Bruce protocol ETT with active or back-up ventricular pacing.
Measured: 3 and 6 months
Exercise performance on 6-minute walk test (6MWT).
Distance walked in metres during 6-minute walk test (6MWT) with active or back-up ventricular pacing.
Measured: 3 and 6 months
Seattle Angina Questionnaire score
Seattle Angina Questionnaire score with active or back-up ventricular pacing. The SAQ is a self-administered, disease-specific measure for patients with CAD that is valid, reproducible, and sensitive to clinical change. This instrument was developed and validated by John Spertus, Director of Cardiovascular Education and Outcomes Research at the Mid America Heart Institute and Professor of Medicine at the University of Missouri - Kansas City. The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life).
Measured: 3 and 6 months
Short-form 36 (SF36) questionnaire score
SF36 Questionnaire score with active or back-up ventricular pacing. The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: 3 and 6 months
Euroqol 5 domain 5 level (EQ5D-5L) questionnaire score
EQ5D-5L Questionnaire score with active or back-up ventricular pacing. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Measured: 3 and 6 months
New York Heart Association (NYHA) classification.
New York Heart Association (NYHA) classification with active or back-up ventricular pacing. The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina.
Measured: 3 and 6 months
Proportion of accidental un-blinding.
Proportion of participants who are accidentally un-blinded to their pacemaker settings during follow-up.
Measured: 12 months.
Proportion of patients requesting cross-over due to symptoms.
Proportion of patients requesting cross-over due to symptoms during the follow-up period.
Measured: 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start2 Jun 2021
- Primary completion20 Feb 2023
- Study completion20 Feb 2023
Why it stopped: Unable to recruit to target
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertrophic CardiomyopathyStudies 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
- Double-blind, randomised, cross-over design
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 11 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, MBChBFRCPMD, Principal investigator, Barts & The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04231032
- Sponsor's protocol ID
- V1.2_25 08 21
- Acronym
- PINCHcm
- Status last verified
- Apr 2023
- First submitted
- 9 Jan 2020
- Last updated
- 6 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paced Dyssynchrony and Myocardial Perfusion IN apiCal Hcm
- ClinicalTrials.gov ID
- NCT04231032
- Acronym / sponsor ID
- PINCHcm / V1.2_25 08 21
- Conditions
- Hypertrophic Cardiomyopathy
- Keywords
- Apical hypertrophic cardiomyopathy, Pacemaker, Perfusion
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit to target
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Study start
- 2 Jun 2021 (actual)
- Primary completion
- 20 Feb 2023 (actual)
- Study completion
- 20 Feb 2023 (actual)
- First posted
- 18 Jan 2020 (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.
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. A relatively common subgroup of HCM patients have apical HCM - a type of heart muscle disease that causes abnormal muscle thickening towards the tip (apex) of the heart. This can impair the heart's own blood flow through the thickened heart muscle. We think this is one of the causes for symptoms such as shortness of breath and chest pain. If medications are ineffective at treating symptoms, there are few further options available, limited to invasive heart surgery.
This study aims to determine if it is possible to improve the blood flow within by altering the settings of patients' permanent pacemakers, dynamic microvascular obstruction is an important cause of perfusion abnormalities in HCM and whether introducing localized dyssynchrony with ventricular pacing improves this. This phased study will include patients with apical HCM that already have implanted pacemaker devices to remove risks associated with device implantation.
The study may provide insights into novel mechanisms for symptoms in HCM and provide new methods for treating a patient group in whom therapeutic options can be extremely limited.
Detailed description
The treatments for people with apical HCM and symptoms are limited but include medicines. The use of a pacemaker in this situation is an experimental treatment which has not yet been fully explored. We believe symptoms are linked with abnormalities in blood flow through the heart muscle at the tip / apex of the heart and wish to see if using a pacemaker can improve such abnormalities. We want to test if this treatment works using a clinical trial to help us decide whether this is a viable treatment option that may be offered to other patients with the condition. The null hypothesis states that there will be no difference in blood flow through the heart muscle with pacing. The alternative hypothesis states that there will be a significant difference in blood flow through the heart muscle with pacing. This was chosen based upon our current knowledge that abnormal blood flow in the heart muscle in apical HCM is linked with abnormal squeeze at the apex / tip and symptoms. Echocardiography pilot data has demonstrated a reduction in squeeze at the apex of the heart when using the pacemaker to cause the heart muscle to contract in a different way.
Our alternative hypothesis therefore is that we can use the pacemaker to reduce squeeze at the apex and improve blood flow through the heart muscle. This is a single centre, prospective pilot study. Because data on acute changes in perfusion with pacing in apical HCM are extremely limited, the most ethical methodology is to perform a two-phase study. Phase A of the study assesses acute changes in blood flow through the heart muscle during different pacemaker settings (active and back-up), looking for potential efficacy of the intervention. Secondary outcomes of Phase A include recruitment rate and proportion of patients willing to proceed to Phase B. Phase B of the study consists of entering those same patients into a randomised double-blind cross-over 6-month follow-up pilot to collect baseline statistical data and assess acceptability of study protocol to design a future study. Here, assessment of further secondary outcomes will allow establishment of baseline statistical data for the design of an outcomes-based clinical trial. Patients will only be entered into phase B of the study if an improvement is seen in myocardial perfusion with pacing during phase A.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Double-blind, randomised, cross-over design
| Arm | Type | Receives |
|---|---|---|
| Active ventricular pacing | Active comparator | Other: Asynchronous dual chamber pacing (DOO) with paced ventricular activationAsynchronous dual chamber pacing (DOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm) |
| Back-up ventricular pacing | Placebo comparator | Other: Asynchronous atrial pacing (AOO) with intrinsic ventricular activationAsynchronous atrial pacing with intrinsic ventricular activation (AOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female, >18 years.
- HCM patients with apical HCM defined as apical hypertrophy with apical LV systolic obliteration and the presence of characteristic ECG changes. Participants with a mixed cardiac phenotype will be considered if they also meet these criteria and do not have resting outflow tract obstruction.
- A programmable intracardiac pacing device with a right atrial lead and an apically / low septal located right ventricular lead.
- Willing and able to provide informed consent.
Key exclusion criteria (7 listed)
- Outflow tract obstruction >50 mmHg at rest due to systolic anterior mitral movement.
- Evidence of high-grade heart block.
- Moderate or severe primary valvular disease.
- Unrevascularised, known, significant coronary disease: the significance of any known coronary disease will be determined after discussion with an independent clinician.
- Atrial fibrillation at the time of randomisation.
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 |
|---|---|---|
| Asynchronous dual chamber pacing (DOO) with paced ventricular activationAlteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation). | Other | Active ventricular pacing |
| Asynchronous atrial pacing (AOO) with intrinsic ventricular activationAlteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation). | Other | Back-up ventricular pacing |
Primary outcome
Myocardial perfusion mapping
Time frame: Acute changes during the CMR scan on Visit 1 (day 1)
Percentage change in regional myocardial perfusion between baseline and pacing measured using myocardial blood flow (MBF) mapping at Cardiovascular Magnetic Resonance (CMR) imaging.
13 secondary outcomes
Proportion successfully completing the CMR scan with interpretable images.
Time frame: After all visit 1 completed (within 6 months)
Myocardial contractility via CMR
Time frame: Acute changes during the CMR scan on Visit 1 (day 1)
Myocardial contractility via echocardiography
Time frame: Acute changes during the echocardiogram scan on Visit 1 (day 1)
Proportion unwilling to proceed to Phase B.
Time frame: After all visit 1 completed (within 6 months).
Recruitment rate.
Time frame: 12 months.
Exercise performance on Bruce protocol treadmill exercise tolerance test (ETT)
Time frame: 3 and 6 months
Exercise performance on 6-minute walk test (6MWT).
Time frame: 3 and 6 months
Seattle Angina Questionnaire score
Time frame: 3 and 6 months
Short-form 36 (SF36) questionnaire score
Time frame: 3 and 6 months
Euroqol 5 domain 5 level (EQ5D-5L) questionnaire score
Time frame: 3 and 6 months
New York Heart Association (NYHA) classification.
Time frame: 3 and 6 months
Proportion of accidental un-blinding.
Time frame: 12 months.
Proportion of patients requesting cross-over due to symptoms.
Time frame: 12 months.
Results and safety
The study was stopped early (reason given: Unable to recruit to target). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Individual participant dataSharing planned: No
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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, MBChBFRCPMD principal investigator
Barts & The London NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Asynchronous dual chamber pacing (DOO) with paced ventricular activation and Asynchronous atrial pacing (AOO) with intrinsic ventricular activation in people with Hypertrophic Cardiomyopathy, 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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 6 Apr 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 was stopped early (reason given: Unable to recruit to target). Results are not available in the source record.
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?
Myocardial perfusion mapping (time frame: Acute changes during the CMR scan on Visit 1 (day 1)). 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 6 Apr 2023.