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STEMIPhase 3RESTORE-MINCT03998319

A Study of Low-dose Intracoronary Thrombolytic Therapy in STEMI (Heart Attack) Patients.

A Phase 3 study testing Tenecteplase (1/3 systemic weight based dose) and Sterile water for injection (WFI) in people with STEMI and Elevated IMR (>32), run by University of Sydney at 22 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
STEMI, Elevated IMR (>32)
What is being tested?
Tenecteplase (1/3 systemic weight based dose) and Sterile water for injection (WFI)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
445 participants
Where
22 sitesin 2 countries
Study dates
14 Oct 2021to 31 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 6 month follow up cardiac MRI

Who cannot join

  • 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
Show all 16Show fewer
  • 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.

Trial locations and contacts

22 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Martin Ng, MBBS (Hons) contact

+614 3407 8507

martin.ng@sydney.edu.au

Rebecca Mister contact

+612 9562 5000 ext. 5342

RESTORE-MI.Study@sydney.edu.au

22 sites in 2 countries

Australia18 sites, 17 recruiting

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

    Jerrett Lau, (08) 7074 1796, jerrett.lau@sa.gov.au

    Recruiting

  • Bankstown-Lidcombe Hospital

    Bankstown, New South Wales, 2200

    Kaleab Asrress, +612 9722 8486, kaleab.asrress@sydney.edu.au

    Not yet recruiting

  • Box Hill Hospital

    Box Hill, Victoria, 3128

    Jaya Chandrasekhar

    Recruiting

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

    Martin Ng, MBBS (Hons), +614 3407 8507, martin.ng@sydney.edu.au

    Recruiting

  • Jessie McPherson Private Hospital

    Clayton, Victoria, 3168

    Robert Gooley

    Recruiting

  • Victorian Heart Hospital

    Clayton, Victoria, 3168

    Robert Gooley

    Recruiting

  • Concord Repatriation General Hospital

    Concord, New South Wales, 2139

    Andy Yong, MBBS, +614 0130 1790, sze.yong@sydney.edu.au

    Recruiting

  • Lyell McEwin Hospital

    Elizabeth Vale, South Australia, 5112

    Purendra Pati, Purendra.Pati@sa.gov.au

    Recruiting

  • The Northern Hospital

    Epping, Victoria, 3076

    William van Gaal, William.vangaal@nh.org.au

    Recruiting

  • Frankston Hospital

    Frankston, Victoria, 3199

    Jamie Layland, (03) 9748 2687, jlayland@phcn.vic.gov.au

    Recruiting

  • Northern Beaches Hospital

    Frenchs Forest, New South Wales, 2086

    Antony Lau

    Not yet recruiting

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

    Sidney Lo, (02) 8738 3051, sidney.lo@health.nsw.gov.au

    Recruiting

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

    Matthew Erickson, 08 6152 6604, matthew.erickson@health.wa.gov.au

    Not yet recruiting

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

    Andrew Boyle, (02) 4921 4720, Andrew.Boyle@health.nsw.gov.au

    Recruiting

  • Royal Perth Hospital

    Perth, Western Australia, 6000

    Jonathan Spiro, (08) 9224 3290, Jonathan.Spiro@health.wa.gov.au

    Recruiting

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

    Sze-Yuan Ooi, (02) 9382 0770, szeyuan.ooi@ehc.com.au

    Not yet recruiting

  • Sunshine Hospital

    Saint Albans, Victoria, 3021

    William Chan, 0435 612 868, william.chan@unimelb.edu.au

    Recruiting

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

    Withdrawn

Other trials in Australia

New Zealand4 sites, 4 recruiting

  • Auckland City Hospital

    Auckland, 1023

    Jithendra Somaratne

    Not yet recruiting

  • Christchurch Hospital

    Christchurch, 4710

    Aniket Puri

    Not yet recruiting

  • Waikato Hospital

    Hamilton, 3240

    Sanjeevan Pasupati

    Recruiting

  • Wellington Hospital

    Wellington, 2820

    Scott Harding

    Not yet recruiting

Other trials in New Zealand

About this study

Official title: 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).

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.

Read the detailed description

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.

Being tested
Tenecteplase (1/3 systemic weight based dose), Sterile water for injection (WFI)
Keywords
STEMI, IMR, microcirculation, microvascular obstruction, myocardial infarction, physiology, angioplasty, PCI, thrombolysis treatment, thrombolysis
Medical subject headings
ST Elevation Myocardial Infarction, Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenecteplase (1/3 systemic weight based dose)Drug

    Also called TNKase

    50mg reconstituted to 20mL for intracoronary infusion at 1/3 weight based dose.

  • Sterile water for injection (WFI)Other

    Placebo comparative arm.

Study groups in NCT03998319
Study groupRoleWhat they receive
Tenecteplase (1/3 systemic weight based dose)ExperimentalTenecteplase 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.
Receives: Drug: Tenecteplase (1/3 systemic weight based dose)
Sterile Water for injection (WFI)Placebo comparatorWater 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.
Receives: Other: Sterile water for injection (WFI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 months

  2. 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.

    Measured: 6 months after primary PCI procedure.

Secondary outcomes (15)

  1. 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.

    Measured: 24 months after primary PCI procedure

  2. 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

    Measured: 24 months after primary PCI procedure

  3. All-cause mortality

    All-cause mortality assessed by physical assessment and medical record review.

    Measured: 24 months after primary PCI procedure

  4. 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).

    Measured: 24 months after primary PCI procedure

  5. Number of incidences of bailout treatment use for no-reflow syndrome

    Use of Bailout treatment for no-reflow syndrome assessed by medical record review

    Measured: 24 months after primary PCI procedure

  6. 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.

    Measured: 24 months after primary PCI procedure

  7. 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.

    Measured: 0-2 hours

  8. Fractional Flow Reserve (FFR)

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

    Measured: 0-2 hours

  9. Coronary Flow Reserve (CFR)

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

    Measured: 0-2 hours

  10. 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.

    Measured: 0-6 months

  11. 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

    Measured: 0-6 months

  12. 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

    Measured: 0-2 hours

  13. 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.

    Measured: 0-2 hours

  14. TIMI corrected frame count

    Thrombolysis in myocardial infarction score with corrected frame count from angiogram to assess myocardial perfusion

    Measured: 0-2 hours

  15. 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).

    Measured: 0-32 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2019
  2. Study start14 Oct 2021
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-Centre double-blind, placebo controlled randomised phase IIIb clinical trial, stratified and balanced between groups on important prognostic factors.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
445 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03998319
Sponsor's protocol ID
CTC0150
Acronym
RESTORE-MI
Status last verified
Sep 2024
First submitted
6 May 2019
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Please refer to the NHMRC Clinical Trials Centre publication and data sharing Standard Operating Procedure.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase (1/3 systemic weight based dose) and Sterile water for injection (WFI) in people with STEMI and Elevated IMR (>32), run by University of Sydney at 22 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Martin Ng, MBBS (Hons) (+614 3407 8507, martin.ng@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03998319.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.

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