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Trial registered on ANZCTR


Registration number
ACTRN12620000785909
Ethics application status
Approved
Date submitted
14/05/2020
Date registered
3/08/2020
Date last updated
3/08/2020
Date data sharing statement initially provided
3/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the role of perhexiline (new medication treatment) in patients with abnormally thickened heart muscle (hypertrophic cardiomyopathy)
Scientific title
Randomised controlled trial of pErhexiline on regreSsion Of Left Ventricular hypErtrophy in patients with symptomatic Hypertrophic CardioMyopathy (RESOLVE-HCM)
Secondary ID [1] 301209 0
Nil known
Universal Trial Number (UTN)
Trial acronym
RESOLVE-HCM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chest pain
 317358 0
Shortness of breath
 317610 0
Abnormally thickened heart muscle 317611 0
Condition category
Condition code
Cardiovascular 315465 315465 0 0
Other cardiovascular diseases
Human Genetics and Inherited Disorders 315687 315687 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventional

Experimental: Perhexiline
Control: Placebo
Mode of administration: Oral tablets
Overall duration of treatment: 12 months

All eligible and consented patients will be randomised to initiation of perhexiline 100mg (tablet) 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. In all other patients, a dose of 100mg/day of trial medication will be continued for the first 30 days. Repeat assay on plasma perhexiline concentration at 30 days will be utilized for individual finer dose titration based on dose adjustment table. Dose titration will then be reviewed by cardiologist (study investigators) and pharmacists for all participants at each visit (i.e. Visit 1 month, 3 months, 6 months, 9 months, and 12 months). Compliance will be assessed by pill count. Paired dosage adjustment in placebo-treated patients will be performed to avoid unblinding.

Reference for dose adjustments:
Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, et al. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005; 112:3280-8.
Intervention code [1] 317511 0
Treatment: Drugs
Comparator / control treatment
Placebo lactose tablet
Control group
Placebo

Outcomes
Primary outcome [1] 323705 0
Change in left ventricular hypertrophy (septal thickness) in symptomatic HCM patients at 12 months following perhexiline therapy as assessed by CMR
Timepoint [1] 323705 0
At 12 months post baseline
Secondary outcome [1] 382681 0
Change in left ventricular mass in symptomatic HCM patients at 12 months following perhexiline therapy via CMR assessment in HCM patients
Timepoint [1] 382681 0
At 12 months post baseline
Secondary outcome [2] 382682 0
Change in oxygen-sensitive CMR in symptomatic HCM patients at 12 months following perhexiline therapy in HCM patients
Timepoint [2] 382682 0
At 12 months post baseline
Secondary outcome [3] 382684 0
Change in echocardiographic left ventricular diastolic function in HCM patients at 12 months following perhexiline therapy.
Timepoint [3] 382684 0
At 12 months post baseline
Secondary outcome [4] 382686 0
Change in NYHA at 12 months in HCM patients
Timepoint [4] 382686 0
At 1, 6, 12 months post baseline
Secondary outcome [5] 383374 0
Change in CCS functional class
Timepoint [5] 383374 0
At 1, 6, 12 months post baseline
Secondary outcome [6] 383375 0
Change in physical activity domain score of SF36
Timepoint [6] 383375 0
At 1, 6, 12 months post baseline
Secondary outcome [7] 383640 0
Major adverse event on heart failure related hospitalisations
Timepoint [7] 383640 0
Monitored over the 12 months period, assessed via patient medical records
Secondary outcome [8] 383641 0
Major adverse event on arrhythmic events
Timepoint [8] 383641 0
Monitored over the 12 months period, assessed via patient medical records
Secondary outcome [9] 383642 0
Major adverse event on abnormal liver function test
(Number of HCM patients receiving perhexiline with deranged liver function tests during the study period)
Timepoint [9] 383642 0
Liver function tests at baseline, 1 month, 6 months and 12 months
Secondary outcome [10] 383643 0
Major adverse event on sudden cardiac death
Timepoint [10] 383643 0
Monitored over the 12 months period, assessed via patient medical records
Secondary outcome [11] 384556 0
Change in strain parameters at 12 months following perhexiline therapy via echochardiography assessment in HCM patients
Timepoint [11] 384556 0
Monitored over the 12 months period

Eligibility
Key inclusion criteria
a) LVEF =/> 55% by echocardiography or CMR during the screening period or within 6 months prior to study entry
b) 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
c) Structural heart disease as evidenced by interventricular septal thickness of (=/> 15 mm) on echocardiography or CMR in the absence of abnormal loading conditions
d) Elevated NT-proBNP (>125 pg/ml)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Any prior echocardiographic or CMR measurement of LVEF <55%
b) Current acute decompensated heart failure requiring hospitalisation and / or augmented medical therapy
c) Cardiac surgery or catheter-based septal reduction therapy planned or having occurred within the past 1 year
d) Patients with a non-CMR conditional pacemaker / implantable cardioverter-defibrillator device
e) History of a known chronic liver disease, peripheral neuropathy, recurrent hypoglycemia
f) Presence of an additional diagnosis that in the opinion of investigator could account for patient's symptoms (e.g. significant pulmonary disease)
g) Serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or lactate dehydrogenase > 2.0 times upper limit of normal
h) Previous adverse reaction to perhexiline at therapeutic plasma levels of the drug
i) Concomitant use of amiodarone, ranolazine or trimetazidine
j) Life-threatening or uncontrolled dysrhythmia
k) Contraindications to CMR, gadolinium, adenosine

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2020
Actual
Date of last participant enrolment
Anticipated
1/09/2021
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 16610 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 16611 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 16613 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 16614 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [5] 16615 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 30206 0
5042 - Bedford Park
Recruitment postcode(s) [2] 30207 0
5011 - Woodville
Recruitment postcode(s) [3] 30209 0
2050 - Camperdown
Recruitment postcode(s) [4] 30210 0
4029 - Herston
Recruitment postcode(s) [5] 30211 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 305721 0
Other
Name [1] 305721 0
SAHMRI
Country [1] 305721 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
1, Flinders Drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 306855 0
None
Name [1] 306855 0
Address [1] 306855 0
Country [1] 306855 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305942 0
The Southern Adelaide Local Health Network
Ethics committee address [1] 305942 0
Ethics committee country [1] 305942 0
Australia
Date submitted for ethics approval [1] 305942 0
23/03/2020
Approval date [1] 305942 0
09/06/2020
Ethics approval number [1] 305942 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102150 0
Prof Joseph Selvanayagam
Address 102150 0
Flinders Medical Centre
1, Flinders Drive
Bedford Park
SA 5042
Country 102150 0
Australia
Phone 102150 0
+61 8 8204 5619
Fax 102150 0
+61 8 8204 5625
Email 102150 0
[email protected]
Contact person for public queries
Name 102151 0
Joseph Selvanayagam
Address 102151 0
Flinders Medical Centre
1, Flinders Drive
Bedford Park
SA 5042
Country 102151 0
Australia
Phone 102151 0
+61 8 8204 5619
Fax 102151 0
+61 8 8204 5625
Email 102151 0
[email protected]
Contact person for scientific queries
Name 102152 0
Joseph Selvanayagam
Address 102152 0
Flinders Medical Centre
1, Flinders Drive
Bedford Park
SA 5042
Country 102152 0
Australia
Phone 102152 0
+61 8 8204 5619
Fax 102152 0
+61 8 8204 5625
Email 102152 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRandomized controlled trial of perhexiline on regression of left ventricular hypertrophy in patients with symptomatic hypertrophic cardiomyopathy (RESOLVE-HCM trial).2021https://dx.doi.org/10.1016/j.ahj.2021.06.010
N.B. These documents automatically identified may not have been verified by the study sponsor.