Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction - Study 25 (ExTRACT-TIMI25)

A Randomized, Double-Blind, Double-Dummy , Parallel Group, Multinational, Clinical Study to Evaluate the Efficacy and Safety of Enoxaparin Versus Unfractionated Heparin in Patients With Acute ST-Segment Elevation Myocardial Infarction Receiving Fibrinolytic Therapy

The primary objective of the study is to determine whether enoxaparin compared to unfractionated heparin will reduce the composite endpoint of all-cause mortality and non-fatal myocardial re-infarction within 30 days after randomization in patients with acute ST-segment elevation myocardial infarction who are eligible to receive fibrinolytic therapy

INCLUSION CRITERIA:

Patients with ST-segment elevation acute myocardial infarction meeting all of the following criteria:

• Male or non-pregnant female greater than or equal to 18 years of age (depending on local regulations, minimal age can vary between 18 and 21 years)
• Onset of prolonged (greater than or equal to 20 min) ischemic symptoms at rest less than or equal to 6 hours prior to randomization
• ST-segment elevation of 0.1 mV in 2 or more limb leads, or 0.2 mV in two (2) or more contiguous precordial leads, or left bundle-branch block
• Planned reperfusion therapy with streptokinase, tenecteplase, alteplase or reteplase
• Written informed consent will be obtained

EXCLUSION CRITERIA:

Cardiovascular

• Evidence of cardiogenic shock at randomization
• Acute pericarditis
• History or symptoms suggestive of aortic dissection
• MI precipitated by obvious provoking factors such as arrhythmia, infection, severe anemia, hyperthyroidism, cocaine, or amphetamine

Hemorrhagic Risk

• Any minor head trauma or any other trauma occurring after the index acute myocardial infarction
• Active or recent (< 3 months) bleeding including gastrointestinal bleeding, known presence of occult blood in the stool, or gross hematuria.
• Any history of bleeding diathesis, coagulopathy, platelet disorder, or thrombocytopenia
• Any single reliable recording of systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg prior to randomization
• Any history of stroke or transient ischemic attack; any history of hemorrhagic cerebrovascular disease
• Any known structural damage or other pathologic process involving the central nervous system
• Any head trauma within 6 months prior to randomization
• Major surgery (including CABG), any ophthalmologic surgery, or non-cutaneous biopsy, or substantial trauma within 3 months prior to randomization
• Traumatic or prolonged cardiopulmonary resuscitation (> 2 minutes) within 2 weeks prior to randomization
• Puncture of a non-compressible vessel (artery or vein) within the 24 hours prior to randomization
• Acute peptic ulcer disease within 3 months prior to randomization

Prior or Concomitant Pharmacologic Therapy

• Administration of abciximab (ReoPro), within the previous 7 days or eptifibatide (Integrilin), or tirofiban (Aggrastat) within the previous 24 hours prior to randomization
• Current therapy with oral anticoagulants, or an International Normalized Ratio of >1.5
• Administration of a low molecular weight heparin within 8 hours prior to randomization.
• Known hypersensitivity to low molecular weight heparins, unfractionated heparin or heparin-like products; allergy to pork or pork products
• Known hypersensitivity and/or contra-indication(s) to fibrinolytic drugs (streptokinase, tenecteplase, alteplase and reteplase)

General

• Known platelet count <100,000 cells/microL or history of heparin-induced thrombocytopenia
• Known clinically significant anemia (Hemoglobin <10 g/dL which is < 6.2 mmol/L)
• Known renal insufficiency with serum creatinine >220 mmol/L (2.5 mg/dL) for men and >175 mmol/L (2.0 mg/dL) for women when assessed prior to baseline examination.
• Advanced neoplastic or other life-threatening disease with a life expectancy of <12 months
• Pregnancy or parturition within the last 90 days or currently breast feeding
• Women of childbearing potential except if post-menopausal, surgically sterile or using accepted method(s) of birth control or having a negative pregnancy test.
• Treatment with other investigational agents in the last 30 days before study entry or previous enrollment in ExTRACT-TIMI 25
• History of drug or alcohol abuse
• Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study
• Any patient unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and who are unlikely to complete the study