Randomised Controlled Trial of pErhexiline on regreSsion Of Left Ventricular hypErtrophy (LVH) in Patients With Symptomatic Hypertrophic CardioMyopathy (RESOLVE-HCM)
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Left Ventricular Hypertrophy (LVH)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Perhexiline
干预措施: Perhexiline (Drug)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Change in Left Ventricular Hypertrophy (LVH)
时间窗: 12 months post baseline
Change in LVH (septal thickness) in symptomatic at 12 months following perhexiline therapy in HCM patients assessed by CMR
次要结局
- Change in oxygen-sensitive Cardiac Magnetic Resonance(12 months post baseline)
- New York Heart Association (NYHA) functional classification(12 months post baseline)
- Major adverse event on heart failure related hospitalisations(Monitored over the 12 months period)
- Change in Left Ventricular (LV) mass(12 months post baseline)
- Canadian Cardiovascular Society (CCS) functional class(12 months post baseline)
- Major adverse event on abnormal liver function test(Liver function tests at baseline, 1 month, 6 months and 12 months)
- Change in left ventricular diastolic function(12 months post baseline)
- Major adverse event on sudden cardiac death(Monitored over the 12 months period)
- Quality of life assessment(12 months post baseline)
- Major adverse event on arrhythmic events(Monitored over the 12 months period)
研究者
Joseph Selvanayagam
Professor
Flinders University