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Trial registered on ANZCTR


Registration number
ACTRN12618000778280
Ethics application status
Approved
Date submitted
12/04/2018
Date registered
9/05/2018
Date last updated
9/05/2018
Type of registration
Prospectively registered

Titles & IDs
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).
Secondary ID [1] 291234 0
None
Universal Trial Number (UTN)
Trial acronym
RESTORE-MI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ST elevation myocardial infarction 302154 0
Condition category
Condition code
Cardiovascular 301768 301768 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will have their Index of Micro-circulatory Resistance (IMR) measured using a standard pressure wire. Patients with an IMR greater then 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).
Intervention code [1] 297234 0
Treatment: Drugs
Comparator / control treatment
Patients with an IMR measurement greater then 32 who are randomised to the placebo arm will receive one intracoronary injection of placebo (water for injection of equal volume to the tenecteplase dose specified above) immediately after their percutaneous coronary intervention (procedure to open narrowed arteries).

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.
Control group
Placebo

Outcomes
Primary outcome [1] 301164 0
Cardiovascular mortality assessed by medical record review
Timepoint [1] 301164 0
24 months after primary PCI procedure
Primary outcome [2] 305293 0
Re-hospitalisation for heart failure assessed by medical record review
Timepoint [2] 305293 0
24 months after primary PCI procedure
Secondary outcome [1] 331904 0
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
Timepoint [1] 331904 0
24 months after primary PCI procedure
Secondary outcome [2] 331905 0
All-cause mortality assessed by physical assessment and medical record review.
Timepoint [2] 331905 0
24 months after primary PCI procedure
Secondary outcome [3] 331906 0
Stroke events will be assessed by medical record review. Assessment will cover all aspects of the stroke event (including type, severity, frequency).
Timepoint [3] 331906 0
24 months after primary PCI procedure
Secondary outcome [4] 331907 0
Use of Bailout treatment for no-reflow syndrome assessed by medical record review
Timepoint [4] 331907 0
24 months after primary PCI procedure
Secondary outcome [5] 331908 0
Major (Type 3 or greater) and minor (Type 2) bleeding as defined by the Bleeding Academic Research Consortium. Assessed by medical record review.
Timepoint [5] 331908 0
24 months after primary PCI procedure
Secondary outcome [6] 331909 0
Index of microcirculatory resistance (IMR) measurement assessed by coronary pressure wire data output review
Timepoint [6] 331909 0
prior to randomisation and immediately after primary PCI
Secondary outcome [7] 331910 0
Fractional Flow Reserve measurement assessed by coronary pressure wire data output review
Timepoint [7] 331910 0
prior to randomisation and immediately after primary PCI
Secondary outcome [8] 331911 0
Coronary Flow Reserve measurement assessed by coronary pressure wire data output review
Timepoint [8] 331911 0
prior to randomisation and immediately after primary PCI
Secondary outcome [9] 331912 0
Wall Motion Score measurement from echocardiogram will be used to assess cardiac function.
Timepoint [9] 331912 0
prior to randomisation, 48 hours and 6 months post primary PCI
Secondary outcome [10] 331913 0
Left ventricular ejection fraction measurement from echocardiogram will be used to assess cardiac function
Timepoint [10] 331913 0
prior to randomisation, 48 hours and 6 months post primary PCI
Secondary outcome [11] 331914 0
Myocardial Blush Grade measurement from angiogram will be used to assess cardiac function.
Timepoint [11] 331914 0
prior to randomisation and post primary PCI
Secondary outcome [12] 331915 0
Thrombolysis in myocardial infarction score from angiogram will be used to assess myocardial perfusion
Timepoint [12] 331915 0
prior to randomisation and post primary PCI
Secondary outcome [13] 344756 0
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
Timepoint [13] 344756 0
prior to primary PCI and at 8, 16, 24 and 32 hours post primary PCI
Secondary outcome [14] 344757 0
Thrombolysis in myocardial infarction score with corrected frame count from angiogram to assess myocardial perfusion
Timepoint [14] 344757 0
prior to randomisation and post primary PCI

Eligibility
Key inclusion criteria
1. Adults presenting with STEMI (defined as chest pain consistent with myocardial ischaemia for at least 30 minutes accompanied by definite ECGs indicating STEMI as defined by ST elevation of 0.1mV or greater in 2 contiguous limb leads or <=0.2mV in 2 contiguous precordial lead) scheduled to undergo primary PCI within 12 hours of symptom onset.
2. (At time of PCI) Patient has received metallic drug-eluting stent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
5. Presence of contraindications to adenosine infusion for IMR measurement including sinus node disease, severe bronchospasm 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.
9. (At time of PCI) Patients who do not undergo primary PCI due to lack of severity of culprit lesion or other reasons.
10. Patients who received GpIIb/IIIa treatment prior to IMR measurement

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment allocation will be balanced using minimisation for the following characteristics; location of infarct (LAD vs. non-LAD), symptom to balloon time (< 3 hours> 3+), hours), known diabetes (yes/no), age (65+ vs. younger than 65), gender, whether the participant had prior MI and study site
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
RESTORE-MI is a multi-centre double-blind placebo-controlled randomised trial.
The first 20 patients will be single-blind placebo-controlled (patient and person assessing are not aware of treatment received).
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The study is powered on the primary endpoint. A total of 1666 subjects will be registered in the study registration database, of whom 800 will be enrolled into the randomised clinical trial and allowing for 1% non-adherence, RESTORE-MI would offer 80% power at 2P=0.05 for a 37% risk reduction in death or rehospitalisation for heart failure over 2 years.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 7520 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 7521 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 7522 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 7523 0
Prince of Wales Hospital - Randwick
Recruitment hospital [5] 7524 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [6] 7525 0
Frankston Hospital - Frankston
Recruitment hospital [7] 7526 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [8] 7527 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [9] 7528 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [10] 10520 0
Royal Perth Hospital - Perth
Recruitment hospital [11] 10521 0
Western Hospital - Footscray - Footscray
Recruitment postcode(s) [1] 15345 0
2050 - Camperdown
Recruitment postcode(s) [2] 15346 0
2139 - Concord
Recruitment postcode(s) [3] 15347 0
2170 - Liverpool
Recruitment postcode(s) [4] 15348 0
2031 - Randwick
Recruitment postcode(s) [5] 15349 0
3084 - Heidelberg
Recruitment postcode(s) [6] 15350 0
3199 - Frankston
Recruitment postcode(s) [7] 15351 0
3065 - Fitzroy
Recruitment postcode(s) [8] 15352 0
6009 - Nedlands
Recruitment postcode(s) [9] 15353 0
6150 - Murdoch
Recruitment postcode(s) [10] 22234 0
6000 - Perth
Recruitment postcode(s) [11] 22235 0
3011 - Footscray
Recruitment outside Australia
Country [1] 8680 0
Singapore
State/province [1] 8680 0
Country [2] 8681 0
New Zealand
State/province [2] 8681 0
Country [3] 8682 0
United States of America
State/province [3] 8682 0
California
Country [4] 8683 0
Korea, Republic Of
State/province [4] 8683 0
Country [5] 10266 0
United Kingdom
State/province [5] 10266 0

Funding & Sponsors
Funding source category [1] 295686 0
Government body
Name [1] 295686 0
National Health and Medical Research Council
Address [1] 295686 0
GPO Box 1421
Canberra ACT 2601
Country [1] 295686 0
Australia
Funding source category [2] 299102 0
Commercial sector/Industry
Name [2] 299102 0
Abbott Pty Ltd
Address [2] 299102 0
299 Lane Cove Road
Macquarie Park, NSW 2113
Australia
Country [2] 299102 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
c/o NHMRC Clinical Trials Centre, Locked bag 77, Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 294529 0
None
Name [1] 294529 0
Address [1] 294529 0
Country [1] 294529 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296996 0
Sydney Local Health District Human Research Ethics Committee – Concord Repatriation General Hospital
Ethics committee address [1] 296996 0
HREC Executive Committee
CRGH Research Office
Ground Floor – Building 20
Concord Repatriation General Hospital
Hospital Road
Concord
NSW 2139
Ethics committee country [1] 296996 0
Australia
Date submitted for ethics approval [1] 296996 0
24/01/2017
Approval date [1] 296996 0
26/06/2017
Ethics approval number [1] 296996 0
CH62/6/2017-017

Summary
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. We 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 hear muscle and improve outcomes.
Impaired microcirculatory perfusion in patients as a result of STelevation 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 left ventricular function.
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 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. An echocardiogram will be performed at baseline and at follow up at 1,6,12,24 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72658 0
Prof Martin Ng
Address 72658 0
Department of Cardiology
Royal Prince Alfred Hospital
Missenden Road, Camperdown NSW 2050
Country 72658 0
Australia
Phone 72658 0
+61 2 9562 5000
Fax 72658 0
Email 72658 0
restore-mi@ctc.usyd.edu.au
Contact person for public queries
Name 72659 0
Ms Annie Yeung
Address 72659 0
NHMRC Clinical Trial Centre
Locked Bag 77
Camperdown
NSW 1450
Country 72659 0
Australia
Phone 72659 0
+61 2 9562 5000
Fax 72659 0
Email 72659 0
restore-mi@ctc.usyd.edu.au
Contact person for scientific queries
Name 72660 0
Prof Martin Ng
Address 72660 0
Department of Cardiology
Royal Prince Alfred Hospital
Missenden Road, Camperdown NSW 2050
Country 72660 0
Australia
Phone 72660 0
+61 2 9562 5000
Fax 72660 0
Email 72660 0
restore-mi@ctc.usyd.edu.au

No data has been provided for results reporting
Summary results
Not applicable