Hypertrophic CardiomyopathyPhase 2RESOLVE-HCMNCT04426578
Role of Perhexiline in Hypertrophic Cardiomyopathy
A Phase 2 study testing Perhexiline in people with Hypertrophic Cardiomyopathy, run by Flinders University at 1 site in Australia.
Trial summary
Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart muscle condition affecting up to 1 in 200 of the general population. It results from mutations in genes encoding components of the contractile apparatus in the heart muscle cell (myocyte). 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?
- Perhexiline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Dec 2020to 1 Aug 2022
- Phase
- Phase 2
- 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
- Left Ventricular Ejection Fraction (LVEF) =/> 55% by echocardiography or CMR during the screening period or within 6 months prior to study entry
- Current / prior symptom(s) of HCM (New York Heart Association [NYHA] functional class II or class III, Canadian Cardiovascular Society [CCS] grade II or grade III) and requiring treatment with ß-blockers and /or non-dihydropyridine calcium antagonists and / or disopyramide for at least 30 days prior to study entry
- Structural heart disease as evidenced by interventricular septal thickness of (= 15 mm) on echocardiography or CMR in the absence of abnormal loading conditions
- Elevated N terminal pro-brain natriuretic peptide (NT-proBNP), >125 pg/ml
Who cannot join
- Any prior echocardiographic or CMR measurement of LVEF <55%
- Current acute decompensated heart failure requiring hospitalisation and / or augmented medical therapy
- Cardiac surgery or catheter-based septal reduction therapy planned or having occurred within the past 1 year
- Patients with a non-CMR conditional pacemaker / implantable cardioverter-defibrillator device
- History of a known chronic liver disease, peripheral neuropathy, recurrent hypoglycemia
- Serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or lactate dehydrogenase > 2.0 times upper limit of normal
Show all 10Show fewer
- Previous adverse reaction to perhexiline at therapeutic plasma levels of the drug
- Concomitant use of amiodarone, ranolazine or trimetazidine
- Life-threatening or uncontrolled dysrhythmia
- Contraindications to CMR, gadolinium, adenosine
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Flinders Medical Centre
Adelaide, South Australia, 5042
Joseph Selvanayagam, joseph.selva@sa.gov.au
Sau Lee, sau.lee@s.gov.au
About this study
Official title: Randomised Controlled Trial of pErhexiline on regreSsion Of Left Ventricular hypErtrophy (LVH) in Patients With Symptomatic Hypertrophic CardioMyopathy (RESOLVE-HCM)
Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart muscle condition affecting up to 1 in 200 of the general population. It results from mutations in genes encoding components of the contractile apparatus in the heart muscle cell (myocyte). These mutations result in increased energy cost of force production for the myocyte which then cumulatively causes a myocardial energy deficit. This myocardial energy deficit is then thought to lead to cardiac hypertrophy ('left ventricular hypertrophy' or LVH) in HCM.
LVH leads to impairments in heart muscle function, heart muscle oxygenation and microvascular blood flow and is the chief driver of patient symptoms in HCM. These symptoms consist of chest pain, shortness of breath, dizziness, fainting episodes or palpitations. Occasionally, the disease may cause sudden cardiac death (SCD). HCM is the most common cause of SCD in young people including competitive athletes. In addition, HCM has been found to result in significant global deterioration in health-related quality of life.
Read more
Treatment of HCM has focused on relief of symptoms by drugs such as ß-blockers which slow the heart rate and improve heart function. However, symptom relief is often incomplete and there is no evidence on the benefit of ß-blockers or related medications to reverse LVH. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor shifts myocardial metabolism to more efficient glucose utilisation and rectifies impaired myocardial energetics. It is currently used to treat angina in patients with coronary artery disease. There is some preliminary evidence that Perhexiline may aid in the improvement of symptoms in patients with HCM. However, the effect of any form of therapy on potential regression of LVH in HCM remains unexplored.
In this randomised double-blind placebo-controlled trial, the investigators will use state of the art cardiac imaging, principally advanced echocardiography and Cardiovascular Magnetic Resonance (CMR) to study the effects of perhexiline on LVH, cardiac function, and oxygenation in symptomatic patients with HCM. The investigators hypothesize that perhexiline will favourably reduce LVH and improve myocardial oxygenation by improving myocardial energetics, and that these putative morphological and functional changes can be accurately measured utilizing echocardiography and CMR. If this pilot study supports the hypothesis, then it will pave the way for a major randomised controlled trial to definitely determine the role of Perhexiline in HCM.
- Conditions
- Hypertrophic Cardiomyopathy
- Being tested
- Perhexiline, Placebo
- Keywords
- Heart function and structure, Hypertrophy, Heart Failure, Medication, Imaging
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Hypertrophy, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerhexilineDrug
Also called Pexsig
All eligible and consented patients will be randomised to initiation of perhexiline 100mg once daily or identical placebo. After 4 days of treatment, a blood sample will be collected to determine plasma perhexiline concentrations: timing of the sample need not be "trough" in view of the long-acting nature of perhexiline. Depending on the blood results, patients might require as little as 50mg/week (slow metabolisers) or as much as 600mg/day (ultra-rapid metabolisers). The initial sample will be utilized primarily to detect presence of hydroxylated metabolite: patients in whom perhexiline is detected in the absence of metabolite will be designated "slow metabolisers" and will have their dosage reduced to 50 mg/week in the first instance. Repeat assay at 30 days will be utilized for individual finer dose titration based on dose adjustment table. Paired dosage adjustment in placebo-treated patients will be performed to avoid unblinding.
Compliance will be assessed by capsule count.
PlaceboOther
All eligible and consented patients will be randomised to initiation of perhexiline 100mg once daily or identical placebo. After 4 days of treatment, a blood sample will be collected to determine plasma perhexiline concentrations: timing of the sample need not be "trough" in view of the long-acting nature of perhexiline. Depending on the blood results, patients might require as little as 50mg/week (slow metabolisers) or as much as 600mg/day (ultra-rapid metabolisers). The initial sample will be utilized primarily to detect presence of hydroxylated metabolite: patients in whom perhexiline is detected in the absence of metabolite will be designated "slow metabolisers" and will have their dosage reduced to 50 mg/week in the first instance. Repeat assay at 30 days will be utilized for individual finer dose titration based on dose adjustment table. Paired dosage adjustment in placebo-treated patients will be performed to avoid unblinding.
Compliance will be assessed by capsule count.
| Study group | Role | What they receive |
|---|---|---|
| Perhexiline | Experimental | Not described Receives: Drug: Perhexiline |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Left Ventricular Hypertrophy (LVH)
Change in LVH (septal thickness) in symptomatic at 12 months following perhexiline therapy in HCM patients assessed by CMR
Measured: 12 months post baseline
Secondary outcomes (10)
Change in Left Ventricular (LV) mass
Change in left ventricular mass in symptomatic at 12 months following perhexiline therapy in HCM patients assessed by CMR
Measured: 12 months post baseline
Change in oxygen-sensitive Cardiac Magnetic Resonance
Change in oxygen-sensitive CMR in symptomatic at 12 months following perhexiline therapy in HCM patients
Measured: 12 months post baseline
Change in left ventricular diastolic function
Change in left ventricular diastolic function at 12 months following perhexiline therapy in HCM patients assessed by echocardiography
Measured: 12 months post baseline
New York Heart Association (NYHA) functional classification
Change in NYHA classification of Class I, II, III and IV at 12 months following perhexiline therapy in HCM patients
Measured: 12 months post baseline
Canadian Cardiovascular Society (CCS) functional class
Change in CCS functional classification of Grade I, II, III and IV at 12 months following perhexiline therapy in HCM patients
Measured: 12 months post baseline
Quality of life assessment
Change in physical activity domain score of Short Form 36 Health Survey Questionnaire (SF36) at 12 months following perhexiline therapy in HCM patients
Measured: 12 months post baseline
Major adverse event on heart failure related hospitalisations
HCM patients admitted with heart failure during the study period
Measured: Monitored over the 12 months period
Major adverse event on arrhythmic events
HCM patients admitted with arrhythmic events during the study period
Measured: Monitored over the 12 months period
Major adverse event on abnormal liver function test
HCM patients with abnormal liver function tests during the study period
Measured: Liver function tests at baseline, 1 month, 6 months and 12 months
Major adverse event on sudden cardiac death
HCM patients with sudden cardiac death during the study period
Measured: Monitored over the 12 months period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start1 Dec 2020
- Primary completion1 Aug 2022 (estimated)
- Study completion1 Aug 2022 (estimated)
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Flinders University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Selvanayagam, Flinders University
- Investigators
- Joseph Selvanayagam, Study chair, Flinders Medical CentreRajiv Ananthakrishna, Principal investigator, Flinders Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04426578
- Sponsor's protocol ID
- HCM2020-01
- Acronym
- RESOLVE-HCM
- Status last verified
- Mar 2021
- First submitted
- 14 May 2020
- Last updated
- 11 Mar 2021
- 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 11 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Controlled Trial of pErhexiline on regreSsion Of Left Ventricular hypErtrophy (LVH) in Patients With Symptomatic Hypertrophic CardioMyopathy (RESOLVE-HCM)
- ClinicalTrials.gov ID
- NCT04426578
- Acronym / sponsor ID
- RESOLVE-HCM / HCM2020-01
- Conditions
- Hypertrophic Cardiomyopathy
- Keywords
- Heart function and structure, Hypertrophy, Heart Failure, Medication, Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Flinders UniversityUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Aug 2022 (estimated)
- Study completion
- 1 Aug 2022 (estimated)
- First posted
- 11 Jun 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 muscle condition affecting up to 1 in 200 of the general population. It results from mutations in genes encoding components of the contractile apparatus in the heart muscle cell (myocyte). These mutations result in increased energy cost of force production for the myocyte which then cumulatively causes a myocardial energy deficit. This myocardial energy deficit is then thought to lead to cardiac hypertrophy ('left ventricular hypertrophy' or LVH) in HCM.
LVH leads to impairments in heart muscle function, heart muscle oxygenation and microvascular blood flow and is the chief driver of patient symptoms in HCM. These symptoms consist of chest pain, shortness of breath, dizziness, fainting episodes or palpitations. Occasionally, the disease may cause sudden cardiac death (SCD). HCM is the most common cause of SCD in young people including competitive athletes. In addition, HCM has been found to result in significant global deterioration in health-related quality of life.
Treatment of HCM has focused on relief of symptoms by drugs such as ß-blockers which slow the heart rate and improve heart function. However, symptom relief is often incomplete and there is no evidence on the benefit of ß-blockers or related medications to reverse LVH. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor shifts myocardial metabolism to more efficient glucose utilisation and rectifies impaired myocardial energetics. It is currently used to treat angina in patients with coronary artery disease. There is some preliminary evidence that Perhexiline may aid in the improvement of symptoms in patients with HCM. However, the effect of any form of therapy on potential regression of LVH in HCM remains unexplored.
In this randomised double-blind placebo-controlled trial, the investigators will use state of the art cardiac imaging, principally advanced echocardiography and Cardiovascular Magnetic Resonance (CMR) to study the effects of perhexiline on LVH, cardiac function, and oxygenation in symptomatic patients with HCM. The investigators hypothesize that perhexiline will favourably reduce LVH and improve myocardial oxygenation by improving myocardial energetics, and that these putative morphological and functional changes can be accurately measured utilizing echocardiography and CMR. If this pilot study supports the hypothesis, then it will pave the way for a major randomised controlled trial to definitely determine the role of Perhexiline in HCM.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perhexiline | Experimental | Drug: Perhexiline |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Left Ventricular Ejection Fraction (LVEF) =/> 55% by echocardiography or CMR during the screening period or within 6 months prior to study entry
- Current / prior symptom(s) of HCM (New York Heart Association [NYHA] functional class II or class III, Canadian Cardiovascular Society [CCS] grade II or grade III) and requiring treatment with ß-blockers and /or non-dihydropyridine calcium antagonists and / or disopyramide for at least 30 days prior to study entry
- Structural heart disease as evidenced by interventricular septal thickness of (= 15 mm) on echocardiography or CMR in the absence of abnormal loading conditions
- Elevated N terminal pro-brain natriuretic peptide (NT-proBNP), >125 pg/ml
Key exclusion criteria (10 listed)
- Any prior echocardiographic or CMR measurement of LVEF <55%
- Current acute decompensated heart failure requiring hospitalisation and / or augmented medical therapy
- Cardiac surgery or catheter-based septal reduction therapy planned or having occurred within the past 1 year
- Patients with a non-CMR conditional pacemaker / implantable cardioverter-defibrillator device
- History of a known chronic liver disease, peripheral neuropathy, recurrent hypoglycemia
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 |
|---|---|---|
| PerhexilineAlso: PexsigAll eligible and consented patients will be randomised to initiation of perhexiline 100mg once daily or identical placebo. After 4 days of treatment, a blood sample will be collected to determine plasma perhexiline concentrations: timing of the sample need not be "trough" in view of the long-acting nature of perhexiline. Depending on the blood results, patients might require as little as 50mg/week (slow metabolisers) or as much as 600mg/day (ultra-rapid metabolisers). The initial sample will be utilized primarily to detect presence of hydroxylated metabolite: patients in whom perhexiline is detected in the absence of metabolite will be designated "slow metabolisers" and will have their dosage reduced to 50 mg/week in the first instance. Repeat assay at 30 days will be utilized for individual finer dose titration based on dose adjustment table. Paired dosage adjustment in placebo-treated patients will be performed to avoid unblinding. Compliance will be assessed by capsule count. | Drug | Perhexiline |
| PlaceboAll eligible and consented patients will be randomised to initiation of perhexiline 100mg once daily or identical placebo. After 4 days of treatment, a blood sample will be collected to determine plasma perhexiline concentrations: timing of the sample need not be "trough" in view of the long-acting nature of perhexiline. Depending on the blood results, patients might require as little as 50mg/week (slow metabolisers) or as much as 600mg/day (ultra-rapid metabolisers). The initial sample will be utilized primarily to detect presence of hydroxylated metabolite: patients in whom perhexiline is detected in the absence of metabolite will be designated "slow metabolisers" and will have their dosage reduced to 50 mg/week in the first instance. Repeat assay at 30 days will be utilized for individual finer dose titration based on dose adjustment table. Paired dosage adjustment in placebo-treated patients will be performed to avoid unblinding. Compliance will be assessed by capsule count. | Other | Placebo |
Primary outcome
Change in Left Ventricular Hypertrophy (LVH)
Time frame: 12 months post baseline
Change in LVH (septal thickness) in symptomatic at 12 months following perhexiline therapy in HCM patients assessed by CMR
10 secondary outcomes
Change in Left Ventricular (LV) mass
Time frame: 12 months post baseline
Change in oxygen-sensitive Cardiac Magnetic Resonance
Time frame: 12 months post baseline
Change in left ventricular diastolic function
Time frame: 12 months post baseline
New York Heart Association (NYHA) functional classification
Time frame: 12 months post baseline
Canadian Cardiovascular Society (CCS) functional class
Time frame: 12 months post baseline
Quality of life assessment
Time frame: 12 months post baseline
Major adverse event on heart failure related hospitalisations
Time frame: Monitored over the 12 months period
Major adverse event on arrhythmic events
Time frame: Monitored over the 12 months period
Major adverse event on abnormal liver function test
Time frame: Liver function tests at baseline, 1 month, 6 months and 12 months
Major adverse event on sudden cardiac death
Time frame: Monitored over the 12 months period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2021.
- 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.
Joseph Selvanayagam study chair
Flinders Medical Centre
Rajiv Ananthakrishna principal investigator
Flinders Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Perhexiline in people with Hypertrophic Cardiomyopathy, run by Flinders University at 1 site in Australia.
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 10 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: status not confirmed, as of the sponsor's last update on 11 Mar 2021. 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 Australia. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joseph Selvanayagam (+61882045619, joseph.selva@sa.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Left Ventricular Hypertrophy (LVH) (time frame: 12 months post baseline). 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 11 Mar 2021.