STEMI Treated With Primary Angioplasty and Intravenous Lovenox or Unfractionated Heparin (UFH) (ATOLL)

Acute STEMI Treated With Primary Angioplasty and Intravenous 0.5 mg/kg Lovenox or UFH to Lower Ischemic and Bleeding Events

Randomized evaluation of enoxaparin (0.5mg/kg IV) versus UFH (50-70IU/kg with GPIIb/IIIa inhibitors; 70-100IU without GPIIb/IIIa inhibitors). Anticoagulation can be continued after the procedure using the same agents as those allocated per randomization (enoxaparin SC, UHF IV or SC)

Study Overview

• Status: Completed
• Conditions: Primary PCI - STEMI
• Intervention / Treatment: Drug: Enoxaparin; Drug: UFH (unfractionated heparin)

Detailed Description

This study is a prospective, multicenter, multinational, randomized, active-control arm trial. The study population consists of subjects with ST-segment elevation MI who are randomized within 24 hours of symptom onset. Subjects presenting between 12 and 24 hours of symptom onset should present with recurrent or persisting chest pain and/or recurrent or persisting ST elevation suggesting ongoing ischemia, and an indication of primary PCI.

Approximately 850 subjects will be enrolled at approximately 50 sites in several countries including Austria, France, Germany and the United States. Informed consent will be obtained from subjects meeting all inclusion and no exclusion criteria prior to any study related procedures. Subjects will be randomized and begin treatment in the Emergency Department or in the ambulance or in the hospital room if in-patient. Eligible subjects will be randomized (1:1) to receive either UFH IV bolus (ACT-adjusted) or enoxaparin 0.50 mg/kg IV bolus without monitoring. Randomization to treatment group will be performed using an interactive voice response system (IVRS). All treatment groups will be given aspirin (160 to 500 mg/day according to local practice) and clopidogrel (300 to 900mg as loading dose according to local practice). All other concomitant medications will be consistent with local standard of care.

• Study Type: Interventional
• Enrollment (Actual): 910
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • La Pitié-Salpétrière Hospital - Cardiology department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be at least 18 years of age.
2. Has experienced continuous ischemic (cardiac) symptoms for at least 20 minutes.
3. Has onset of symptoms of qualifying acute MI within the past 24 hours, and planned for primary PCI. Patients presenting between 12 and 24 hours of symptom onset should still have an indication for primary PCI, i.e. persistent ischemic symptom and/or persistent or recurrent ST elevation

4. Has an ECG indicative of an acute STEMI showing:

   • ≥ 2 mm ST elevation in 2 or more contiguous precordial ECG leads (anterior infarction); or
   • ≥ 1 mm ST elevation in 2 or more contiguous limb ECG leads (other infarction); or
   • New or presumably new left bundle branch block (LBBB)
5. Shock patients are eligible (but not patients with prolonged cardiac arrest)
6. Be willing to provide informed consent (informed consent may be provided by a legally authorized representative if the patient is not able to provide it).
7. Agree to comply with all protocol-specified procedures, including protocol-mandated follow-up

Exclusion Criteria:

1. Use of UFH or LMWH or any other anticoagulant agent (Vit K antagonists, fondaparinux, bivalirudin) within 48 hours prior to randomization
2. Thrombolytic therapy within the previous 48 hours
3. Known or suspected pregnancy in women of childbearing potential
4. History of hypersensitivity or contraindication to heparin or LMWH
5. Contraindication to primary PCI or any excessive bleeding risk (e.g. recent surgery) or suspected active internal bleeding
6. Coexistent condition associated with a limited life expectancy at short term (e.g. advanced cancer)
7. Prolonged (> 10 minutes) cardiopulmonary resuscitation (CPR)
8. Treatment with other investigational agents or devices within the previous 30 days, planned use of investigational drugs or devices, or previous enrolment in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Enoxaparin	Drug: Enoxaparin; ENOXAPARIN IV 0.5 mg.kg
Active Comparator: 2; UFH	Drug: UFH (unfractionated heparin); UFH IV 50-70 IU if GP IIbIIIa or 70-100IU if no GP IIbIIIa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality or Complications of MI or Procedure failure or Non-CABG major bleeding during hospitalization	administration

Secondary Outcome Measures

Outcome Measure	Time Frame
major bleeding during hospitalization	during hospitalization and at 6 months
the ischemic end-point of death, reinfarction, refractory ischemia and/or urgent revascularization	day30 and 6 months
efficacy objectives are each individual ischemic endpoint of the primary objective as well as the composite ischemic end-point of death, complications of MI or procedure failure.	day 30 and 6 months
the composite of major and minor bleeding during hospitalization	during hospitalization and months 6

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Gilles MONTALESCOT, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Montalescot G, Zeymer U, Silvain J, Boulanger B, Cohen M, Goldstein P, Ecollan P, Combes X, Huber K, Pollack C Jr, Benezet JF, Stibbe O, Filippi E, Teiger E, Cayla G, Elhadad S, Adnet F, Chouihed T, Gallula S, Greffet A, Aout M, Collet JP, Vicaut E; ATOLL Investigators. Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial. Lancet. 2011 Aug 20;378(9792):693-703. doi: 10.1016/S0140-6736(11)60876-3.
• Silvain J, O'Connor SA, Yan Y, Kerneis M, Hauguel-Moreau M, Zeitouni M, Overtchouk P, Ankri A, Brugier D, Vicaut E, Ecollan P, Galier S, Collet JP, Montalescot G; ATOLL Investigators. Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated Heparin. Am J Cardiovasc Drugs. 2018 Dec;18(6):503-511. doi: 10.1007/s40256-018-0294-z.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 16, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (Estimate): July 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2012
• Last Update Submitted That Met QC Criteria: December 17, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: STEMI; Primary PCI; Anticoagulation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Calcium heparin
• Other Study ID Numbers: P071101; EUDRACT: 2007-007676-42

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No