Role of Perhexiline in Hypertrophic Cardiomyopathy
关键词
抽象
日期
| 最后验证: | 04/30/2020 |
| 首次提交: | 05/13/2020 |
| 提交的预估入学人数: | 06/08/2020 |
| 首次发布: | 06/10/2020 |
| 上次提交的更新: | 06/08/2020 |
| 最近更新发布: | 06/10/2020 |
| 实际学习开始日期: | 07/31/2020 |
| 预计主要完成日期: | 07/31/2022 |
| 预计完成日期: | 07/31/2022 |
状况或疾病
干预/治疗
Drug: Perhexiline
Other: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: Perhexiline | Drug: Perhexiline 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. |
| Placebo Comparator: Placebo | Other: Placebo 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. |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: 1. Left Ventricular Ejection Fraction (LVEF) =/> 55% by echocardiography or CMR during the screening period or within 6 months prior to study entry 2. 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 3. Structural heart disease as evidenced by interventricular septal thickness of (= 15 mm) on echocardiography or CMR in the absence of abnormal loading conditions 4. Elevated N terminal pro-brain natriuretic peptide (NT-proBNP), >125 pg/ml Exclusion Criteria: 1. Any prior echocardiographic or CMR measurement of LVEF <55% 2. Current acute decompensated heart failure requiring hospitalisation and / or augmented medical therapy 3. Cardiac surgery or catheter-based septal reduction therapy planned or having occurred within the past 1 year 4. Patients with a non-CMR conditional pacemaker / implantable cardioverter-defibrillator device 5. History of a known chronic liver disease, peripheral neuropathy, recurrent hypoglycemia 6. Serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or lactate dehydrogenase > 2.0 times upper limit of normal 7. Previous adverse reaction to perhexiline at therapeutic plasma levels of the drug 8. Concomitant use of amiodarone, ranolazine or trimetazidine 9. Life-threatening or uncontrolled dysrhythmia 10. Contraindications to CMR, gadolinium, adenosine |
结果
主要结果指标
1. Change in Left Ventricular Hypertrophy (LVH) [12 months post baseline]
次要成果指标
1. Change in Left Ventricular (LV) mass [12 months post baseline]
2. Change in oxygen-sensitive Cardiac Magnetic Resonance [12 months post baseline]
3. Change in left ventricular diastolic function [12 months post baseline]
4. New York Heart Association (NYHA) functional classification [12 months post baseline]
5. Canadian Cardiovascular Society (CCS) functional class [12 months post baseline]
6. Quality of life assessment [12 months post baseline]
7. Major adverse event on heart failure related hospitalisations [Monitored over the 12 months period]
8. Major adverse event on arrhythmic events [Monitored over the 12 months period]
9. Major adverse event on abnormal liver function test [Liver function tests at baseline, 1 month, 6 months and 12 months]
10. Major adverse event on sudden cardiac death [Monitored over the 12 months period]
