A Randomised, Double-blind, Placebo-controlled Study Investigating the Effects of Dietary Nitrate on Vascular Function, Platelet Reactivity and Restenosis in Stable Angina
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Difference between groups in In-stent late loss, where late loss is defined as the difference between the minimum luminal diameter (MLD).
研究概览
简要总结
The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. Whilst this procedure has revolutionised treatment the incidence of secondary events remains a concern. These repeat events are due in part to continued enhanced platelet reactivity, endothelial dysfunction and a phenomenon called 'restenosis' i.e. the stent becomes blocked ultimately requiring another expensive and risky procedure. In this study it will be determined whether a once daily inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis.
详细描述
To address the aims a proof-of-concept study will be conducted to ascertain whether a dietary nitrate approach might prove useful adjunctive therapy improving vascular function in patients with stable angina post elective angioplasty.
Design: A prospective randomised, single-centre, double-blind, placebo-controlled trial
Setting: Patients with stable angina and single/multiple coronary artery stenosis undergoing elective percutaneous coronary intervention (PCI) who are haemodynamically stable (systolic BP>100 mmHg). These patients will be recruited at The Barts Health Heart Centre, based at St. Bartholomew's Hospital. This is one of the biggest centres in the United Kingdom, serving a population of almost two million people from The City of London and The North East up to the M25 and is a 24/7 centre performing approximately 2000 non-primary angioplasties a year.
The study will take place in the Clinical Trials Unit, William Harvey Heart Centre.
Target population: A total of 300 patients (male and female, age 18-85) with stable angina as per requirements indicated above. Follow-up will take place in the Clinical Trials Unit, William Harvey Research Institute.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with stable angina diagnosed by a cardiologist on optimal medical therapy undergoing angioplasty to treat residual symptoms.
- •Patients able and willing to give their written informed consent.
- •Patients undergoing successful PCI procedure.
排除标准
- •Unstable ischaemic heart disease, with an episode of chest pain in less than 24 hours.
- •Patients who have had previous coronary artery bypass surgery (CABG), if they are undergoing angioplasty within a non-native vessel.
- •Patients undergoing angioplasty with a bio-absorbable stent.
- •Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
- •Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
- •Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
- •Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study related procedures).
- •Severe acute infection, or significant trauma (burns, fractures).
- •Pregnancy. This will be tested by urine human chorionic gonadotropin (hCG) measurement
- •History of alcohol or drug abuse within the past 6 months.
- •A history of heart failure New York Heart Association (NYHA) class 3-4 or severe left ventricular dysfunction (left ventricular ejection fraction of <30%) regardless of symptom status.
- •Systemic autoimmune disease such as rheumatoid arthritis, connective tissue disease, or other conditions known to be associated with chronic inflammation such as inflammatory bowel disease.
- •Patients who have donated > 500mls blood within 56 days prior to study medication administration.
- •Anaemia with Hb <10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation.
- •A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder) or HIV.
- •Abnormal liver function due to acute or chronic liver conditions 3 x upper limit of normal at screening.
- •Renal impairment with creatinine clearance (eGFR) of 35ml/min at screening.
- •If patients are on mouthwash, they must be willing to stop using this at least 1 week before the start of the study and throughout the duration that they are involved in the study.
研究组 & 干预措施
Nitrate-rich beetroot juice
70 ml of a beetroot juice concentrate containing ~5 mmol nitrate
干预措施: Beetroot Juice (Dietary Supplement)
Nitrate-deplete beetroot juice
70 ml of a beetroot juice concentrate that is nitrate-depleted
干预措施: Beetroot Juice (Dietary Supplement)
结局指标
主要结局
Difference between groups in In-stent late loss, where late loss is defined as the difference between the minimum luminal diameter (MLD).
时间窗: 6 months +/- 1 month post intervention
次要结局
- Difference from baseline within the group and between groups in endothelial function assessed by flow-mediated dilatation of the brachial artery at 6 months compared to pre-procedure assessment.(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups in restenosis rate (diameter >50%).(6 months post intervention)
- Difference from baseline within the group and between groups in plasma and erythrocyte nitrite reductase.(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups in target vessel revascularisation (TVR).(6 months post intervention)
- Difference from baseline within the group and between groups in Interleukin-6 (IL-6).(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups in in-segment late loss.(6 months post intervention)
- Difference from baseline within the group and between groups in changes in plasma xanthine oxidase activity.(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups high-sensitivity C-reactive protein (hsCRP).(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups in platelet activation (P-Selectin and platelet-monocyte aggregates).(6 months and 12 months post intervention)
- Difference from baseline within the group and between groups in platelet aggregation ex vivo (ADP, collagen, arachidonic acid).(6 months and 12 months post intervention)
- Difference from baseline between groups in major adverse cardiac events (i.e. Myocardial Infarction, death, Cerebrovascular Accident, Target Vascular Revascularisation).(6 months, 12 months and 24 months post intervention)
- Difference from baseline within the group and between groups in inflammatory markers.(6 months and 12 months post intervention)