A phase 3 study of low-dose intracoronary thrombolytic therapy in STEMI (heart attack) patients

• Register: ANZCTR
• Last refreshed on: 9 October 2023
• Main ID: ACTRN12618000778280
• Date of registration: 09/05/2018
• Prospective Registration: Yes
• Primary sponsor: University of Sydney
• Public title: A phase 3 study of low-dose intracoronary thrombolytic therapy in STEMI (heart attack) patients
• Scientific title: Restoring Microcirculatory Perfusion in ST-Elevation Myocardial Infarction (STEMI): A randomised trial to evaluate the efficacy of low-dose intracoronary tenecteplase in STEMI patients with high microvascular resistance post-percutaneous coronary intervention (PCI).
• Date of first enrolment: 16/10/2018
• Target sample size: 50
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12618000778280.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Efficacy;
• Phase: Phase 3

Countries of recruitment

Australia

Contacts

• Name: Prof Martin Ng

• Name: Ms RESTORE-MI Trial Coordinator

Key inclusion & exclusion criteria

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.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

ST elevation myocardial infarction;
ST elevation myocardial infarction

Cardiovascular - Coronary heart disease

Intervention(s)

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).

Primary Outcome(s)

Cardiovascular mortality assessed by medical record review[ 24 months after primary PCI procedure]

Re-hospitalisation for heart failure assessed by medical record review[ 24 months after primary PCI procedure]

Secondary Outcome(s)

Thrombolysis in myocardial infarction score with corrected frame count from angiogram to assess myocardial perfusion[ prior to randomisation and post primary PCI ]

Use of Bailout treatment for no-reflow syndrome assessed by medical record review[ 24 months after primary PCI procedure]

Coronary Flow Reserve measurement assessed by coronary pressure wire data output review [ prior to randomisation and immediately after primary PCI]

Thrombolysis in myocardial infarction score from angiogram will be used to assess myocardial perfusion [ prior to randomisation and post primary PCI ]

Fractional Flow Reserve measurement assessed by coronary pressure wire data output review [ prior to randomisation and immediately after primary PCI]

Left ventricular ejection fraction measurement from echocardiogram will be used to assess cardiac function[ prior to randomisation, 48 hours and 6 months post primary PCI ]

Index of microcirculatory resistance (IMR) measurement assessed by coronary pressure wire data output review[ prior to randomisation and immediately after primary PCI]

Major Adverse Coronary Events (these are combination events involving cardiovascular death, non-fatal MI, non-fatal stroke and unstable angina) assessed from physical assessment and medical record review[ 24 months after primary PCI procedure]

Myocardial Blush Grade measurement from angiogram will be used to assess cardiac function. [ prior to randomisation and post primary PCI ]

All-cause mortality assessed by physical assessment and medical record review.[ 24 months after primary PCI procedure]

Cardiac function as a composite measure of cardiac enzymes including troponin T, creatine kinase, creatine kinase-MB and high sensitivity troponin T, from blood samples collected during hospitalisation [ prior to primary PCI and at 8, 16, 24 and 32 hours post primary PCI]

Major (Type 3 or greater) and minor (Type 2) bleeding as defined by the Bleeding Academic Research Consortium. Assessed by medical record review.[ 24 months after primary PCI procedure]

Stroke events will be assessed by medical record review. Assessment will cover all aspects of the stroke event (including type, severity, frequency). [ 24 months after primary PCI procedure]

Wall Motion Score measurement from echocardiogram will be used to assess cardiac function. [ prior to randomisation, 48 hours and 6 months post primary PCI ]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Abbott Pty Ltd

National Health and Medical Research Council

Ethics review

Status: Approved
Approval date: 26/06/2017
Contact:

Results

• Results available: Yes
• Date Posted: 03/05/2022
• Date Completed: 05/09/2023