A Randomised Trial to Evaluate the Efficacy of Low-dose Intracoronary Tenecteplase in ST-Elevation Myocardial Infarction (STEMI) Patients With High Microvascular Resistance Post-percutaneous Coronary Intervention (PCI).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 445
- 试验地点
- 22
- 主要终点
- To compare the number of participants who experience cardiovascular mortality and rehospitalisation for heart failure at 24 months in those given tenecteplase with those given placebo (Cardiac MRI cohort only)
研究概览
简要总结
Heart attacks are caused by a blood clot blocking the blood vessels of the heart, preventing blood getting to the heart muscle. Opening up the artery with a balloon (angioplasty) and a small mesh tube (stent) although life saving can cause this clot to break up and get washed downstream, which can make the heart attack worse. The investigators can measure the amount of damage caused to the microcirculation by calculating the IMR (Index of Microcirculatory resistance).
This can be measured by a wire in the coronary artery with a pressure sensor at the tip. If the IMR is elevated, it is suggestive of extensive microcirculatory damage. A clot dissolving medicine can be administered in the artery to try and reduce the IMR which can reduce damage to the heart muscle and improve outcomes.
Impaired microcirculatory perfusion in patients as a result of ST-elevation myocardial infarction (STEMI) is associated with poor clinical outcomes. This project seeks to identify patients with impaired microcirculatory perfusion after STEMI and to assess whether acute improvement in microcirculatory perfusion in these patients by the use of intracoronary thrombolytic therapy results in improved clinical outcomes.
详细描述
Patients presenting to the participating hospitals with a heart attack will be approached to participate in the study. After angioplasty has been performed, the IMR will be measured in the infarct related artery. If the IMR is >32 patients will be randomised to receive intracoronary clot dissolving therapy in the form of low dose tenecteplase (TNK) or water as a placebo. Patients who have an IMR ≤32 will be followed up in a registry. Cardiac enzymes will be measured at baseline and discharge. Randomised participants will receive a cardiac MRI at discharge (3-7 days post primary PCI) and at 6 months post PCI. All participants will be followed up at 30 days, and 6, 12 and 24 months following discharge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All parties involved will be blinded.
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
- •Adult men and women aged over 18 who present with STEMI within 6 hours of symptom onset. Patients will be eligible if they have symptoms consistent with myocardial ischaemia (chest pain, dyspnoea) for at least 20 minutes accompanied by definite ECGs indicating STEMI as defined by Australian National Heart Foundation (NHF) guidelines
- •Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances
- •Able to personally read and understand the Participant Information and Consent Form and provide written, signed and dated informed consent to participate in the study
- •(At time of PCI) Patient has received metallic drug-eluting stent
- •Participant consents to have a 3-7 day (discharge) and 5 month follow up cardiac MRI
排除标准
- •At the time of screening and/or prior to randomisation, no known;
- •Previous coronary bypass grafting
- •Other residual lesions with ≥50% diameter stenosis in the culprit vessel
- •Prior myocardial infarction in the target territory
- •Presence of contraindications to thrombolytic therapy (including history of stroke and recent brain surgery active internal bleeding; history of cerebrovascular accident; intracranial or intraspinal surgery, or trauma within 2 months; intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; and severe uncontrolled hypertension)
- •Presence of contraindications to adenosine infusion for IMR measurement including sinus node disease, moderate to severe bronchoconstrictive disease and second or third-degree atrioventricular (AV) block
- •Diagnosis of metastatic disease
- •Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- •Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
- •Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
- •Participation in any investigational study in the previous 30 days
- •Other exclusion criteria:
- •(Cardiac MRI cohort only) Presence of contraindications to contrast enhanced MRI including severe claustrophobia, pregnancy, pacemakers, non-MRI compatible aneurysm clips, defibrillators and estimated glomerular filtration rate of <30mL/min.
- •(At time of PCI)
- •Patients who received GpIIb/IIIa treatment prior to IMR measurement
- •Patients who do not undergo primary PCI due to lack of severity of culprit lesion or other reasons.
研究组 & 干预措施
Tenecteplase (1/3 systemic weight based dose)
Tenecteplase will be reconstituted in 20mL sterile water for injection at 1/3 of the weight based dose, and administered by intracoronary infusion over 3 minutes.
干预措施: Tenecteplase (1/3 systemic weight based dose) (Drug)
Sterile Water for injection (WFI)
Water for injection will be prepared to 20mL over an equivalent time period to the reconstitution time of the experimental arm, in order to maintain the blind, and administered by intracoronary infusion over 3 minutes.
干预措施: Sterile water for injection (WFI) (Other)
结局指标
主要结局
To compare the number of participants who experience cardiovascular mortality and rehospitalisation for heart failure at 24 months in those given tenecteplase with those given placebo (Cardiac MRI cohort only)
时间窗: 24 months
Cardiovascular mortality and rehospitalisation for heart failure assessed by medical record review.
To compare MI size as a % of LV mass and intramyocardial bleeding rates in participants at 6 months post PCI in those given low dose tenecteplase with those given placebo.
时间窗: 6 months after primary PCI procedure.
MI size and intramyocardial bleeding rates will be assessed upon cardiac MRI at discharge (3-7 days post procedure) as a baseline measure, and at 6 months post-PCI.
次要结局
- Number of participants who experience individual components of the primary endpoint: (a) cardiovascular mortality at 24 months, (b) rehospitalisation for heart failure at 24 months;(24 months after primary PCI procedure)
- All-cause mortality(24 months after primary PCI procedure)
- Fractional Flow Reserve (FFR)(0-2 hours)
- Myocardial Blush Grade(0-2 hours)
- Cardiac enzyme measurements(0-32 hours)
- TIMI Myocardial Perfusion Grade(0-2 hours)
- Number of stroke events(24 months after primary PCI procedure)
- Number of incidences of bailout treatment use for no-reflow syndrome(24 months after primary PCI procedure)
- Index of Microcirculatory Resistance (IMR)(0-2 hours)
- Coronary Flow Reserve (CFR)(0-2 hours)
- Number of Major Adverse Cardiac Events (MACE)(24 months after primary PCI procedure)
- Occurrence of major (Type 3 or greater) and minor (Type 2) bleeding as defined by the Bleeding Academic Research Consortium(24 months after primary PCI procedure)
- Wall Motion Score(0-6 months)
- Left ventricular ejection fraction (LVEF)(0-6 months)
- TIMI corrected frame count(0-2 hours)