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

NCT03998319 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CTC0150
• Study Type: interventional
• Target: 445
• Locations: 2 countries
• Sites: 22

Brief 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 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.

Conditions

STEMI; Elevated IMR (>32)

Keywords

STEMI; IMR; microcirculation; microvascular obstruction; myocardial infarction; physiology; angioplasty; PCI; thrombolysis treatment; thrombolysis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months after primary PCI procedure.

Secondary Outcomes (15)

• 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

• Number of Major Adverse Cardiac Events (MACE)

  24 months after primary PCI procedure

• All-cause mortality

  24 months after primary PCI procedure

• 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

Other Outcomes (9)

• DNA analyses (Subject to funding)

  0-6 months

• MicroRNA analyses (Subject to funding)

  0-6 months

• Vasoactive markers (Subject to funding)

  0-6 months

Study Arms (2)

Tenecteplase (1/3 systemic weight based dose)

EXPERIMENTAL

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)

Sterile Water for injection (WFI)

PLACEBO COMPARATOR

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)

Interventions

Tenecteplase (1/3 systemic weight based dose) DRUG

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

Also known as: TNKase

Tenecteplase (1/3 systemic weight based dose)

Sterile water for injection (WFI) OTHER

Placebo comparative arm.

Sterile Water for injection (WFI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• (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.

Sponsors & Collaborators

• University of Sydney: lead

Study Sites (22)

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, 2200, Australia

NOT YET RECRUITING

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

RECRUITING

Northern Beaches Hospital

Frenchs Forest, New South Wales, 2086, Australia

NOT YET RECRUITING

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

RECRUITING

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

RECRUITING

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

NOT YET RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

WITHDRAWN

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

RECRUITING

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

RECRUITING

Jessie McPherson Private Hospital

Clayton, Victoria, 3168, Australia

RECRUITING

Victorian Heart Hospital

Clayton, Victoria, 3168, Australia

RECRUITING

The Northern Hospital

Epping, Victoria, 3076, Australia

RECRUITING

Frankston Hospital

Frankston, Victoria, 3199, Australia

RECRUITING

Sunshine Hospital

Saint Albans, Victoria, 3021, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

NOT YET RECRUITING

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

Auckland City Hospital

Auckland, 1023, New Zealand

NOT YET RECRUITING

Christchurch Hospital

Christchurch, 4710, New Zealand

NOT YET RECRUITING

Waikato Hospital

Hamilton, 3240, New Zealand

RECRUITING

Wellington Hospital

Wellington, 2820, New Zealand

NOT YET RECRUITING

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Myocardial Infarction

Interventions

Tenecteplase; Injections

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Martin Ng, MBBS (Hons)

  Royal Prince Alfred Hospital, Sydney, Australia

  STUDY CHAIR

• Andy Yong, MBBS

  Concord Repatriation General Hospital

  STUDY CHAIR

• Anthony Keech, MBBS

  National Health and Medical Research Council, Australia

  STUDY CHAIR

• William Fearon, MD

  Stanford University

  STUDY CHAIR

• Jamie Layland, MBBS

  Peninsula Health

  STUDY CHAIR

• Harvey White, FRCS

  Green Lane Cardiovascular Service

  STUDY CHAIR

Central Study Contacts

Martin Ng, MBBS (Hons)

CONTACT

+614 3407 8507; martin.ng@sydney.edu.au

Rebecca Mister

CONTACT

+612 9562 5000; RESTORE-MI.Study@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties involved will be blinded.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-Centre double-blind, placebo controlled randomised phase IIIb clinical trial, stratified and balanced between groups on important prognostic factors.

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: June 26, 2019
• Study Start: October 14, 2021
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (4); AU (18)