Clinical trial NCT00077792: Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction - Study 25 (ExTRACT-TIMI25)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Acute ST-Segment Elevation
Keywords: Receiving fibrinolytic therapy
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2004-02-16
Enrollment: 20506
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Composite of all-cause mortality and non-fatal myocardial re-infarction
Secondary outcomes:
measure: Composite of all-cause mortality, non-fatal myocardial re-infarction, and myocardial ischemia leading to urgent revascularization and non-fatal disabling stroke
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: sanofi-aventis administrative Office
city: Macquarie Park
country: Australia
facility: sanofi-aventis Australia & New Zealand administrative office
city: Vienna
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Minsk
country: Belarus
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Sofia
country: Bulgaria
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Shangaï
country: China
facility: Sanofi-Aventis Administrative Office
city: Zagreb
country: Croatia
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Tallinn
country: Estonia
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi- Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Causeway Bay
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Dublin
country: Ireland
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Amman
country: Jordan
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Riga
country: Latvia
facility: Sanofi-Aventis Administrative Office
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Administrative Office
city: Vilnius
country: Lithuania
facility: Sanofi-Aventis Administrative Office
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Lysaker
country: Norway
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Singapore
country: Singapore
facility: Sanofi-Aventis Administrative Office
city: Bratislava
country: Slovakia
facility: Sanofi-Aventis Administrative Office
city: Midrand
country: South Africa
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
city: Bangkok
country: Thailand
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-aventis adminsitrative office
city: Montevideo
country: Uruguay
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References:
citation: Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, Budaj A, Lopez-Sendon JL, Guneri S, Jiang F, White HD, Fox KA, Braunwald E; ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006 Apr 6;354(14):1477-88. doi: 10.1056/NEJMoa060898. Epub 2006 Mar 14.
citation: Morrow DA, Antman EM, Fox KA, White HD, Giugliano R, Murphy SA, McCabe CH, Braunwald E; ExTRACT-TIMI 25 Investigators. One-year outcomes after a strategy using enoxaparin vs. unfractionated heparin in patients undergoing fibrinolysis for ST-segment elevation myocardial infarction: 1-year results of the ExTRACT-TIMI 25 trial. Eur Heart J. 2010 Sep;31(17):2097-102. doi: 10.1093/eurheartj/ehq098. Epub 2010 Apr 17.