None listed
Conditions
Brief summary
In patients with ST-elevated myocardial infarction, percutaneous coronary intervention restores epicardial coronary blood flow. Yet half of these patients continue to have impaired perfusion on the myocardial level and this portends a poor prognosis. Poor microcirculatory reperfusion has also been shown to be a predictor of death or rehospitalisation for heart failure after three years in post-PCI STEMI patients . The development of the index of microcirculatory resistance (IMR) by the study team has allowed easy assessment of the coronary microcirculation. Small, randomised trials have shown that intracoronary administration of the thrombolytic agent streptokinase improved the status of the coronary microcirculation and in turn reduced infarct size, preserved left ventricular dimensions and left ventricular function at six months follow-up. Despite these promising results, there has been no adequately powered clinical trial to confirm the long-term benefits of improving microvascular perfusion. PILOT STUDY COHORT: The study hypothesis is that in 50 adults with STEMI who have undergone primary PCI and have an IMR score greater than 32, low dose tenecteplase, compared with placebo treatment, improves long term clinical outcomes, benefits other clinical cardiovascular measures, and does not increase rates of MACE.
Interventions
All patients will have their Index of Micro-circulatory Resistance (IMR) measured using a standard pressure wire. Patients with an IMR greater than 32 who are randomised to the treatment arm will receive one intracoronary injection of tenecteplase (one-third of the weight-based systemic dose) after their percutaneous coronary intervention (procedure to open narrowed arteries).
The systematic dose is sourced by the manufacturer on the product information form.
The intracoronary injection will be
All patients will have their Index of Micro-circulatory Resistance (IMR) measured using a standard pressure wire. Patients with an IMR greater than 32 who are randomised to the treatment arm will receive one intracoronary injection of tenecteplase (one-third of the weight-based systemic dose) after their percutaneous coronary intervention (procedure to open narrowed arteries). The systematic dose is sourced by the manufacturer on the product information form. The intracoronary injection will be administered by an authorised study investigator or study nurse. The administration will be supervised by a separated study investigator or study nurse. The study treatment will be blinded (patients and the study team will not know which treatment arm was assigned).
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Adult men and women aged over 18 who present with STEMI within 12 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 NHF guidelines; 2) Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances; 3) 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. 4) (At time of PCI) Patient has received metallic drug-eluting stent
Exclusion criteria
At the time of screening or prior to randomisation, no known: 1) Previous coronary bypass grafting 2) Patients with other residual lesions with >50% diameter stenosis in the culprit vessel 3) Patients with prior myocardial infarction in the target territory 4) 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) 5) Presence of contraindications to adenosine infusion for IMR measurement including sinus node disease, moderate to severe bronchoconstrictive disease and second or third-degree AV block 6) Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety 7) Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol 8) 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. 9) (Imaging (CMR) substudy only) Presence of contraindications to contrast enhanced MRI including pacemakers, metallic prostheses and estimated glomerular filtration rate of <30mL/min. 10) (At time of PCI) Patients who do not undergo primary PCI due to lack of severity of culprit lesion or other reasons.
Outcome results
None listed