A Phase 3 interventional study of Tenecteplase (1/3 systemic weight based dose) and Sterile water for injection (WFI) in STEMI and Elevated IMR (>32), sponsored by University of Sydney. Recruiting at 22 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-27.
Sponsored by University of Sydney · Phase 3, Interventional, and Other
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.
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.
667 studies on the registry are indexed under ST Elevation Myocardial Infarction; 180 are open to participants now.
This study's planned enrollment of 445 is above the median of 194 across 427 interventional studies indexed under ST Elevation Myocardial Infarction.
Browse ST Elevation Myocardial Infarction studies →University of Sydney is the lead sponsor of 91 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
At the time of screening and/or prior to randomisation, no known;
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)
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.
Drug: Tenecteplase (1/3 systemic weight based dose)
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.
Other: Sterile water for injection (WFI)
50mg reconstituted to 20mL for intracoronary infusion at 1/3 weight based dose.
Also known as: TNKase
Placebo comparative arm.
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)
Cardiovascular mortality and rehospitalisation for heart failure assessed by medical record review.
Time frame: 24 months
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.
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.
Time frame: 6 months after primary PCI procedure.
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;
Cardiovascular mortality and rehospitalisation for heart failure assessed by medical record review, respectively.
Time frame: 24 months after primary PCI procedure
Number of Major Adverse Cardiac Events (MACE)
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
Time frame: 24 months after primary PCI procedure
All-cause mortality
All-cause mortality assessed by physical assessment and medical record review.
Time frame: 24 months after primary PCI procedure
Number of stroke events
Stroke events will be assessed by medical record review. Assessment will cover all aspects of the stroke event (including type, severity, frequency).
Time frame: 24 months after primary PCI procedure
Number of incidences of bailout treatment use for no-reflow syndrome
Use of Bailout treatment for no-reflow syndrome assessed by medical record review
Time frame: 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
Major (Type 3 or greater) and minor (Type 2) bleeding as defined by the Bleeding Academic Research Consortium. Assessed by medical record review.
Time frame: 24 months after primary PCI procedure
Index of Microcirculatory Resistance (IMR)
Index of microcirculatory resistance (IMR) measurement assessed by coronary pressure wire data output review. This is a simple unit scale, with a higher number indicating a worse outcome with a score of more than 25 indicating abnormal microcirculatory function in the heart.
Time frame: 0-2 hours
Fractional Flow Reserve (FFR)
Fractional Flow Reserve measurement assessed by coronary pressure wire data output review prior to randomisation and immediately after primary PCI
Time frame: 0-2 hours
Coronary Flow Reserve (CFR)
Coronary Flow Reserve measurement assessed by coronary pressure wire data output review, prior to randomisation and immediately after primary PCI.
Time frame: 0-2 hours
Wall Motion Score
The score is measured by simple unit scale (1 = normal, 2 = hypokinetic (muscle impaired), 3= akinetic (muscle dead)). Each of the 16 segments of the hearts is scored, with the total being divided by 16 to derive the score.
Time frame: 0-6 months
Left ventricular ejection fraction (LVEF)
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
Time frame: 0-6 months
Myocardial Blush Grade
Myocardial Blush Grade measurement from angiogram will be used to assess cardiac function. The score goes from 0 to 3, with 3 being normal and 0 being absence of myocardial blush
Time frame: 0-2 hours
TIMI Myocardial Perfusion Grade
Thrombolysis in myocardial infarction score from angiogram will be used to assess myocardial perfusion. This score goes from 0 to 3, 3 indicates normal flow within the artery and 0 indicates a complete coronary occlusion.
Time frame: 0-2 hours
TIMI corrected frame count
Thrombolysis in myocardial infarction score with corrected frame count from angiogram to assess myocardial perfusion
Time frame: 0-2 hours
Cardiac enzyme measurements
Cardiac enzyme levels including troponin T, creatine kinase, creatine kinase-MB and high sensitivity troponin T, from blood samples collected during the hospitalisation period (prior to primary PCI and at 8, 16, 24 and 32 hours post primary PCI).
Time frame: 0-32 hours
DNA analyses (Subject to funding)
Samples of whole blood will be used for DNA analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
MicroRNA analyses (Subject to funding)
Samples of whole blood will be used for microRNA analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Vasoactive markers (Subject to funding)
Samples of whole blood will be used for vasoactive marker analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Inflammatory markers (Subject to funding)
Samples of whole blood will be used for inflammatory marker analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Angiogenic markers (Subject to funding)
Samples of whole blood will be used for angiogenic marker analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Liver function (Subject to funding)
Samples of whole blood will be used for liver function analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Thyroid Function (Subject to funding)
Samples of whole blood will be used for thyroid function analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Lipid profile (Subject to funding)
Samples of whole blood will be used for lipid profile analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Lipoprotein profile (Subject to funding)
Samples of whole blood will be used for lipoprotein profile analyses at baseline, post-PCI, discharge and 6 month follow up (6m follow up for Randomised participants only).
Time frame: 0-6 months
Plan to share: No — Please refer to the NHMRC Clinical Trials Centre publication and data sharing Standard Operating Procedure.
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University of Sydney