A Trial of Low-dose Adjunctive alTeplase During prIMary PCI

• Status: Completed
• Trial end date: 2019-05-08
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the safety and efficacy of reduced doses (10 mg and 20 mg) of intra-coronary alteplase compared with placebo as an adjunct to PCI in reducing MVO and its consequences in high risk patients with STEMI.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: National Institute for Health Research, United Kingdom; University of Glasgow
• Treatments: Tissue Plasminogen Activator

Criteria

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.