A Trial of Low-dose Adjunctive alTeplase During prIMary PCI (T-TIME)
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ClinicalTrials.gov Identifier: NCT02257294 |
Recruitment Status :
Completed
First Posted : October 6, 2014
Last Update Posted : September 6, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Myocardial Infarction | Drug: Alteplase Other: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 440 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Randomised, Double Blind, Placebo-controlled, Parallel Group Trial of Low-dose Adjunctive alTeplase During prIMary PCI |
Actual Study Start Date : | March 2016 |
Actual Primary Completion Date : | July 2018 |
Actual Study Completion Date : | May 8, 2019 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Control Arm
two placebo vials
|
Other: Placebo
Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI. |
Active Comparator: Arm A
Alteplase 10mg and placebo vial
|
Drug: Alteplase
Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI.
Other Name: Actilyse Other: Placebo Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI. |
Active Comparator: Arm B
Alteplase 10mg and alteplase 10mg
|
Drug: Alteplase
Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI.
Other Name: Actilyse |
- The amount of MVO (% of Left Ventricular (LV) mass) revealed by late (10 - 15 min) gadolinium contrast enhancement MRI 2 days post-MI. [ Time Frame: 2-7 days ]Amount of MVO (% of LV mass) revealed by late gadolinium contrast-enhanced MRI 10-15 minutes after contrast administration on an MRI scan performed 2-7 days post-MI.
- Angiogram [ Time Frame: 0-2 hours ]TIMI Coronary flow grade at the end of PCI; TIMI blush grade at the end of PCI; TIMI frame count at the end of PCI; TIMI thrombus grade at the end of PCI
- ECG [ Time Frame: 0-2 hours ]% ST segment resolution on the 12-lead ECG (pre- vs. 60 mins post-reperfusion with primary PCI)
- Haematology [ Time Frame: 24 hours ]Coagulation
- MRI [ Time Frame: 2-7 days ]Late MVO (presence/absence); Infarct size; Myocardial salvage index (infarct size/area-at-risk); LV end-diastolic volume (LVEDV); LV end-systolic volume (LVESV); LV ejection fraction (LVEF); Myocardial haemorrhage (presence/absence); Myocardial haemorrhage extent (% of LV)
- Safety [ Time Frame: 2-7 days ]Acute cerebral (stroke) and systemic (GI, peripheral) bleeding (if any) with alteplase; Coagulation (fibrinogen concentration);
- MRI [ Time Frame: 12 weeks ]Infarct size; Myocardial salvage index (final infarct size/initial area-at-risk); LV end-diastolic volume (LVEDV); LV end-systolic volume (LVESV); LV ejection fraction (LVEF);
- ECG [ Time Frame: 12 weeks ]ECG for final infarct size
- Biochemistry [ Time Frame: 12 weeks ]Troponin T; NT-pro BNP
- Quality of Life [ Time Frame: 12 weeks ]EQ5D-5L assessment (2-7 days, 12 weeks)
- Histopathology (sub-study) [ Time Frame: 0 hours ]Fibrin histopathology in thrombus aspirate
- Angiogram [ Time Frame: 0-2 hours ]Intra-procedural changes in TIMI Coronary Flow Grade; Intra-procedural changes in TIMI blush grade; Intra-procedural changes in TIMI Frame Count; Intra-procedural changes in TIMI Thrombus Grade; Intra-procedural thrombotic events
- Coronary Physiology (sub-study) [ Time Frame: 0-2 hours ]IMR; CFR
- Optical Coherence Tomography (sub-study) [ Time Frame: 0-2 hours ]Thrombus area
- Biochemistry [ Time Frame: 24 hours ]Blood chemistry (standard of care blood tests)
- Haematology [ Time Frame: 24 hour ]Haemoglobin (standard of care blood tests)
- Safety [ Time Frame: 24 hours ]Haemoglobin (standard of care blood tests)
- ECG [ Time Frame: 12 weeks ]Surrogate ECG measures of infarct size - Anderson ST Acuteness score and Selvester QRS score; Acuteness of the ECG changes - Anderson Wilkins score;
- MRI [ Time Frame: 12 weeks ]First pass MVO extent (% of LV); Early MVO extent (% of LV) on 1 min post-gadolinium contrast enhanced MRI , adjusted for area-at-risk at baseline; LV remodelling index (minimum infarct wall thickness / maximum remote zone thickness mid-diastole); LV diastolic myocardial wall thickness to volume; LV sphericity index at end diastole (maximal longitudinal LV diameter (i.e. tip mitral valve to LV index) / maximal short-axis diameter); LV sphericity index at end-systole (maximal longitudinal LV diameter (i.e. tip mitral valve to LV apex) / maximal short-axis diameter); LV wall motion; Myocardial strain; Myocardial haemorrhage; Myocardial perfusion in the infarct zone; Myocardial perfusion in the remote zone; Infarct zone perfusion indexed to remote zone perfusion; Extracellular volume in the infarct zone; Extracellular volume in the remote zone; Extracellular in the infarct core; LV wall motion;
- Quality of life [ Time Frame: 2 years ]Blood chemistry (standard of care blood tests); EQ5D-5L (52 weeks)
- Health outcomes [ Time Frame: 3 years ]Death; MI; Heart Failure; Stroke/TIA; Acute bleeds

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Males aged ≥ 18 years; females ≤ 18 years not of child bearing potential (defined as women who are post-menopausal or permanently sterilised (e.g. hysterectomy, tubal occlusion, bilateral salpingectomy)
- Acute myocardial infarction (symptoms onset ≤ 6 hours) with persistent ST-segment elevation or recent left bundle branch block
- Coronary artery occlusion (TIMI coronary flow grade 0 or 1) OR Impaired coronary flow (TIMI flow grade 2, slow but complete filling) in the presence of definite angiographic evidence of thrombus (TIMI grade 2+)
- Proximal-mid culprit lesion location in a major coronary artery (ie the right, left anterior descending, intermediate or circumflex coronary artery)
- Radial artery access
Exclusion Criteria:
- Shock (systolic blood pressure <90 mmHg with clinical signs of peripheral hypoperfusion despite adequate filling)
- Normal coronary flow grade (TIMI flow grade 3) at initial angiography
- Functional coronary collateral supply (Rentrop grade 2/3) to culprit artery
- Multivessel PCI intended before the day 2-7 MRI Scan
- Non-cardiac co-morbidity with expected survival <1 year
- Estimated body weight <60kg
- Contra-indication to contrast-enhanced MRI
- Pacemaker
- Implantable defibrillator
- estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.73m²
- previous infarction in the culprit artery (known or suspected clinically, e.g. wall motion abnormality revealed by echocardiography)
- Significant bleeding problem either at present or within the past 6 months
- Patients with current concomitant oral anticoagulant therapy (INR > 1.3), including apixaban, dabigatran and rivaroxaban
- Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial, or spinal surgery)
- Known Haemorrhagic diathesis
- Severe uncontrolled hypertension >180/110 mmHg not controlled by medical therapy
- Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current STEMI)
- Recent trauma to the head or cranium (<2 months)
- Prolonged cardiopulmonary resuscitation (>2 minutes) within past 2 weeks
- Acute pericarditis and/or subacute bacterial endocarditis e.g. valve mass or vegetation revealed by echocardiography
- Acute pancreatitis
- Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
- Arterial aneurysm and known arterial/venous malformation
- Neoplasm with increased bleeding risk
- Any known history of haemorrhagic stroke or stroke of unknown origin
- Known history of ischaemic stroke or transient ischaemic attack <6 months
- Dementia
- Hypersensitivity to gentamicin
- Women of child-bearing potential (i.e. pre-menopause) or breast feeding
- Previous randomisation to this study or participation in a study with an investigational drug or medical device within 90 days prior to randomisation
- Incapacity or inability to provide informed consent
- requirement for immunosuppressive drug therapy at any time during the past 3 months; whether administered orally, subcutaneously or intravenously. This would include corticosteroids (but not inhaled or topical), drugs used following transplantation (e.g. tacrolimus, cyclosporine), anti-metabolite therapies (e.g. mycophenolic acid (Myfortic), azathioprine, leflunomide (Arava)), and immunomodulators including biologics (e.g. adalimumab (HUMIRA), etanercept (Enbrel), aldesleukin), and DMARDS (cyclophosphamide. methotrexate, etc). Please note that this list is not exhaustive and a requirement for other immunosuppressive drugs not listed would also exclude the patient.
- active or prophylactic treatment with oral or parenteral antibiotic, antifungal or antiviral therapy to prevent or treat infection.
- any anti-cancer treatment (excluding surgery as this is covered above) at any time during the past 3 months including chemotherapy, radiotherapy and treatment with biologics such as Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors (e.g. bevacizumab, pazopanib). This list is not exhaustive and the sponsor or CI should be contacted for advice if required.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257294
United Kingdom | |
Edinburgh Royal Infirmary | |
Edinburgh, United Kingdom | |
Golden Jubilee National Hospital | |
Glasgow, United Kingdom, G81 4HX | |
Leeds General Infirmary | |
Leeds, United Kingdom, LS1 3EX | |
Glenfield Hospital | |
Leicester, United Kingdom | |
Liverpool Heart and Chest Hospital | |
Liverpool, United Kingdom | |
Barts Health Centre, St Bartholomew's Hospital | |
London, United Kingdom, EC1A 7BE | |
University Hospital of South Manchester NHS Foundation Trust | |
Manchester, United Kingdom, M23 9LT | |
James Cook University Hospital | |
Middlesbrough, United Kingdom | |
Freeman Hospital | |
Newcastle, United Kingdom, NE7 7DN | |
University Hospital Southampton NHS Foundation Trust | |
Southampton, United Kingdom, SO16 6TD | |
Heart and Lung Centre, New Cross Hospital | |
Wolverhampton, United Kingdom, WV10 0QP |
Principal Investigator: | Colin Berry, Prof | University of Glasgow |
Responsible Party: | NHS Greater Glasgow and Clyde |
ClinicalTrials.gov Identifier: | NCT02257294 |
Other Study ID Numbers: |
GN12CA450 12/170/45 ( Other Grant/Funding Number: EME ) |
First Posted: | October 6, 2014 Key Record Dates |
Last Update Posted: | September 6, 2019 |
Last Verified: | September 2019 |
Myocardial Infarction Infarction Ischemia Pathologic Processes Necrosis Myocardial Ischemia Heart Diseases |
Cardiovascular Diseases Vascular Diseases Tissue Plasminogen Activator Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |