A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) With Aspirin in Patients Presenting With Anterior STEMI Treated With Primary PCI
试验速览
- 阶段
- 2 期
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Index of Myocardial Resistance (IMR)
研究概览
简要总结
This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients.
详细描述
The very early benefit of ticagrelor in STEMI is co-mediated by adenosine cardioprotection maintaining/ improving myocardial microcirculatory function, as well as via platelet inhibition or possibly other pleiotropic effects.
Ticagrelor increases circulating adenosine by reducing cellular re-uptake. Adenosine is a cardioprotective agent that utilizes cellular survival kinase pathways that may have beneficial effects on the microcirculation and myocardium in patients presenting with STEMI. Adenosine is currently used as a treatment for no-reflow and improves MVO post-STEMI when administered during PPCI. A recent study of healthy volunteers has confirmed that non-invasive coronary flow is augmented by ticagrelor and that this is mediated by adenosine. The Investigators propose that the very early beneficial effects of Ticagrelor in ACS may be adenosine mediated cardioprotection, rather than only due to an antiplatelet effect. This important research is original and a natural progression of the ticagrelor story. It expands the adenosine hypothesis and mode of action of ticagrelor and addresses a novel cardioprotective/ microcirculatory mechanism of action.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind until the point of primary endpoint.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI.
- •Male or female adult patient aged 18 - 90 years old
- •Anterior STEMI (ST elevation ≥ 2mmHg in contiguous chest leads) with chest pain symptom onset < 12 hours
排除标准
- •Cardiogenic shock*
- •Previous anterior myocardial infarction
- •Unfavourable coronary anatomy for PCI: left main / surgical or distal coronary disease
- •Already prescribed Ticagrelor at the time of admission
- •Factors affecting study drug administration/ absorption: vomiting or allergy
- •Concomitant use of potent CYP3A4 inhibitors/ inducers (e.g ketoconazole and rifampicin) or CYP3A4 substrates with a narrow therapeutic window (e.g. cisapride and ergot alkaloids) or simvastatin / lovostatin >40mg oral dose.
- •Severe bleeding diathesis or current active bleeding*
- •History of intracranial haemorrhage
- •Moderate or Severe hepatic impairment
- •Severe asthma or bradycardia/ complete heart block (contraindications to adenosine)*
- •Severe co-morbidity with a life expectancy < 3 months.
- •Women of child bearing potential (as determined by direct questioning of the patient to confirm and this will be documented in the medical notes).
- •Patients that are found to have any excluding factor (e.g., unfavourable coronary anatomy for PCI) or develop any excluding factor (e.g., vomiting or cardiogenic shock) before the point of final IMR assessment will be discontinued from the study and followed up at discharge and by telephone at 3 and 12 months for adverse event monitoring purposes only.
研究组 & 干预措施
Ticagrelor
Patients will receive Ticagrelor 180mg (2 x 90mg tablets)
干预措施: Ticagrelor (Drug)
Placebo
Patients will receive Placebo (2 matching tablets)
干预措施: Placebo (Other)
结局指标
主要结局
Index of Myocardial Resistance (IMR)
时间窗: Baseline to end of PPCI procedure.
To compare final Index of Myocardial Resistance (IMR) at the end of the PPCI procedure between the two arms.
次要结局
- ST segment resolution(Baseline to end of PPCI procedure.)
- OCT quantified clot volume pre/post PPCI(Baseline to end of PPCI procedure.)
- TIMI flow and TMBG pre/post PPCI(Baseline to end of PPCI procedure.)
- ACF and AMR pre/post PPCI(Baseline to end of PPCI procedure.)
- Baseline IMR and change in IMR during PPCI(Baseline to end of PPCI procedure.)
- Cardiac troponin - I and CKMB levels at 0, 12 and 24 hours(Baseline to 24 hours.)
- Cardiac MRI microvascular obstruction between 24-48 hours and infarct size at 3 months(Baseline to 3 months.)