Does Allopurinol Regress Left Ventricular Hypertrophy in Patients With Treated Essential Hypertension?
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- The change LV mass index with allopurinol versus placebo.
研究概览
简要总结
The presence of Left ventricular hypertrophy (LVH) confers high cardiovascular risk in hypertensive patients. LVH remains highly prevalent even when blood pressure (BP) is controlled. There is increasing evidence that a major non-haemodynamic contributor to LVH is oxidative stress. Allopurinol is known to markedly reduce oxidative stress.
This pragmatic randomised double blind placebo controlled trial will examine whether allopurinol (300 mg bd) regresses LV mass as assessed by cardiac magnetic resonance (CMR) in 66 patients with treated hypertension but who have persisting LVH.
Endothelial and vascular function will also be assessed via flow mediated dilatation (FMD) and pulse wave analysis respectively (PWA) and plasma biomarkers of oxidative stress will be measured. The treatment (allopurinol or placebo) will last 12 months.
详细描述
Does Allopurinol regress Left Ventricular Hypertrophy in Patients with Treated Essential Hypertension?
People with high blood pressure are at increased risk of heart complications. One of the biggest problems is that the muscle wall of the heart thickens. The medical term for this is Left Ventricular Hypertrophy (LVH). LVH makes the heart less efficient and patients with LVH are at a 10 times greater risk of heart complications than those without it.
A goal of treating high blood pressure is to reduce the strain on the heart and to try to decrease this thickening of the heart wall. However, even when blood pressure is treated and is under control, LVH can persist, and as there are no symptoms to LVH it can go undetected.
Currently the only way to reduce LVH would be to lower blood pressure (BP) even further. This can cause side-effects from low BP such as dizziness and nausea.
It has previously been shown that a drug allopurinol, which is usually used to treat gout had the remarkable side effect of being able to reduce this thickening of the heart wall in patients who had kidney disease or diabetes. The aim now is to see if patients with high blood pressure and LVH may also benefit from treatment with allopurinol. If LVH can be reduced using allopurinol, this might be a new way to reduce cardiac risk in these patients without needing to lower BP even further.
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
- •are aged over 18 years
- •previously diagnosed with essential hypertension
- •been on stable antihypertensive therapy for at least 3 months prior to study screening
- •have screening ambulatory bloods pressure monitoring (ABPM) or home based BP monitoring if ABPM not tolerated with daytime average systolic <135mmHg
- •have screening echocardiography based diagnosis of left ventricular hypertrophy (LVH) based on American society of echocardiography (ASE) criteria (males >115g/m2, females >95g/m2)
排除标准
- •documented intolerance to allopurinol
- •left Ventricular Ejection Fraction <45% on echocardiography screening
- •severe aortic stenosis on echocardiography screening
- •active gout (i.e. flare within two years) or currently on allopurinol
- •severe hepatic disease
- •renal disease; chronic kidney disease (CKD) class 3B or worse
- •on azathioprine, 6 mercaptopurine, or theophylline
- •malignancy (receiving active treatment) or other life threatening diseases
- •pregnant or lactating women
- •any contraindication to magnetic resonance imaging (MRI) (claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention).
- •patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded.
- •patients who are unable to give informed consent
- •any other considered by a study physician to be inappropriate for inclusion.
研究组 & 干预措施
Allopurinol
Patients treated with Allopurinol 300mg daily for first month then 300mg twice daily for remainder trial.
干预措施: Allopurinol (Drug)
Placebo tablet
Microcrystalline cellulose one tablet daily for first month then twice daily for remainder of trial.
干预措施: Placebo (Drug)
结局指标
主要结局
The change LV mass index with allopurinol versus placebo.
时间窗: 12 months
Baseline and repeat CMRI examinations at baseline (+/- 2 weeks) and after the final 12 month (+/- 2 weeks) visit will be performed on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of left ventricular mass. This single observer will analyze all the scans. The reproducibility of the left ventricular mass assessment using MRI will be derived for this observer. The change LV mass index in participants treated with allopurinol will be compared with placebo.
次要结局
- Measure a change in left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction.(Twelve months)
- The change in C reactive protein (CRP), brain natriuretic peptide (BNP), troponin I (TnI), oxidized lactate dehydrogenase (oxidized LDH) and Procollagen carboxyl end peptide (PICP) with allopurinol versus placebo.(12 months)
- Change in average 24 hour BP control with allopurinol versus placebo.(12 months)
- % change in brachial artery diameter and change in augmentation index with allopurinol versus placebo.(12 months)
- The change in LV mass after subtracting the volume of scar with allopurinol versus placebo.(12 months)