The STREAM Percutaneous Coronary Intervention Anticoagulant Sub-study

This study has been completed.
Sponsor:
Collaborators:
Sanofi
Boehringer Ingelheim
Information provided by (Responsible Party):
Robert Welsh, University of Alberta
ClinicalTrials.gov Identifier:
NCT00882635
First received: April 15, 2009
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to assess the safety and efficacy of Enoxaparin and Unfractionated Heparin in St Elevation Myocardial Infarction patients undergoing primary percutaneous coronary intervention.


Condition Intervention Phase
Acute Myocardial Infarction
Drug: enoxaparin
Drug: Unfractionated heparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The STrategic Reperfusion Early After Myocardial Infarction (STREAM) Anticoagulation With Enoxaparin vs. Unfractionated Heparin in Primary PCI Sub-study.

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Adequacy of anticoagulation with enoxaparin (anti-Xa levels ≥ 0.5 U/ml to 1.5 U/ml) vs. unfractionated heparin (ACT - ≥200 - 250 seconds with concomitant GP IIb/IIIa antagonist and ACT - ≥250 - 350 seconds without concomitant GP IIb/IIIa antagonist). [ Time Frame: During Primary PCI ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Composite of major bleeding (non-CABG), death, cardiogenic shock, and congestive heart failure [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • ECG & angiographic measures before and after primary PCI [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: October 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enoxaparin Drug: enoxaparin

Enoxaparin 0.5 mg/kg IV bolus (Regardless of whether the investigator has chosen to initiate concomitant GP IIb/IIIa antagonist; provision for additional IV enoxaparin to be administered if elapsed time to PCI exceeds 2 hours (from original IV dose) - enoxaparin 0.25 mg/kg IV will be administered At the discretion of the treating physician, if sustained anticoagulation is required then enoxaparin subcutaneously will be administered - enoxaparin 1.0 mg/kg SQ q 12 hours.

Maintenance dose adjustment for renal insufficiency - creatinine clearance < 30 ml/min, sc enoxaparin should be administered at 1.0 mg / kg / q24 hours. No adjustment of IV dose is required in case of renal insufficiency

Active Comparator: Unfractionated heparin Drug: Unfractionated heparin
Unfractionated heparin 70 u/kg IV bolus (consistent with ASSENT 4 PCI) Baseline ACT will be draw at time of sheath insertion - With use of GP IIb/IIIa antagonist additional UFH will be administered to achieve an ACT of ≥200 - 250 seconds If IIb/IIIa is not utilized - additional UFH will be administered to achieve an ACT of ≥250-350 seconds At the discretion of the treating physician if sustained anticoagulation is required:UFH infusion 12/u/kg/hr IV infusion to commence

Detailed Description:

Past research in stable patients with coronary artery disease and those with non-ST elevation acute coronary syndromes (NSTEMI) has demonstrated the safety and efficacy of enoxaparin as an anticoagulant strategy in patients undergoing percutaneous coronary intervention 1-3.

In patients with ST-elevations myocardial infarction (STEMI) receiving pharmacological reperfusion (fibrinolysis), enoxaparin has been shown to be an attractive alternative to unfractionated heparin based upon past modest scale trials (HART-2, ENTIRE TIMI 23, ASSENT-3, ASSENT-3+)4-6. These results were definitively extended by the ExTRACT-TIMI 25 trial which compared fibrinolysis with unfractionated heparin versus enoxaparin in 20,506 patients with STEMI 7. The primary endpoint of death and re-MI occurred in 9.9% of patients with enoxaparin and 12.0% of patients in the unfractionated heparin group (17% RR, p<0.001); major bleeding occurred in 2.1% and 1.4% respectively (p<0.001). This was achieved using a dose reduction strategy in the elderly (>75yrs) that omitted the intravenous enoxaparin bolus and decreased the subcutaneous injection to 0.75 mg/kg. After initial fibrinolysis, fewer patients underwent PCI through 30 days in the enoxaparin group versus the unfractionated heparin group (22.8% vs 24.2%, p=0.027). Among those who underwent PCI (n=4674) by 30 days the primary endpoint occurred in 10.7% with enoxaparin versus 13.8% unfractionated heparin randomization (0.77 RR, p<0.001); major bleeding was not different (1.4% vs. 1.6%, p=NS) 8.

Despite existing data in stable coronary artery disease, NSTEMI, and STEMI patients treated with fibrinolysis there is limited data regarding the approach to anticoagulation therapy with enoxaparin in those STEMI patients undergoing primary PCI. Within a sub-study of the Which Early ST Elevation Myocardial Infarction Therapy study (WEST) we undertook systematic anti-Xa sampling to address the adequacy of anticoagulation with an enoxaparin based regime9, 10. WEST patients undergoing primary PCI received aspirin, clopidogrel, and subcutaneous enoxaparin (1mg/kg) at the time of randomization. Subsequent administration of intravenous enoxaparin and abciximab at the time of PCI was encouraged. Those receiving supplemental intravenous enoxaparin (0.3 - 0.5 mg/kg) in addition to subcutaneous enoxaparin achieved anti-Xa levels > 0.5 units/ml (the proposed therapeutic concentration). Amongst those receiving 1 mg/kg of enoxaparin subcutaneous at randomization and 0.3 mg/kg intravenous enoxaparin at time of PCI, none had excessive anticoagulation (anti-Xa > 1.5 units/ml) suggesting that this may be an attractive dosing strategy.

Recently a non-randomized comparison of unfractionated heparin and enoxaparin within the FINNESSE study was presented in STEMI patients undergoing primary PCI. Preliminary reports indicate superior outcomes amongst those receiving enoxaparin 0.5mg/kg intravenous as compared to unfractionated heparin intravenously.

The STREAM study provides a unique and important opportunity to acquire randomized safety and efficacy data on anticoagulation with enoxaparin vs. unfractionated heparin in STEMI patients undergoing primary PCI.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age equal or greater than 18 years
  2. Onset of symptoms of STEMI < 3 hours prior to randomisation
  3. 12-lead ECG (ST elevation will be measured from the J point) indicative of an acute STEMI: >2 mm ST elevation across 2 contiguous precordial leads (best 2 of V1-V6) or leads I, AVL for a minimum combined total of >4 mm ST elevation,or >3 mm ST elevation in 2 contiguous inferior leads (best 2 of II, III, AVF) for a minimum combined total of > 6 mm ST elevation.
  4. Informed consent received

Exclusion Criteria:

  1. PCI (1st balloon inflation) expected to commence < 60 minutes from diagnosis (qualifying ECG) or inability to arrive at the cardiac catheterization laboratory (1st balloon inflation) within 3 hours after randomisation.
  2. Anticipated or obvious problem with vascular access.
  3. Previous CABG
  4. Left bundle branch block or ventricular pacing.
  5. Patients with cardiogenic shock - Killip Class 4
  6. Patients with a body weight < 55 kg (known or estimated)
  7. Uncontrolled hypertension, defined as blood pressure measurement > 180/110 mm Hg (systolic BP > 180 mm Hg and/or diastolic BP > 110 mm Hg) confirmed on repeat measures (2 documented measurements at any time) prior to randomization.
  8. Known use oral anticoagulants (warfarin or coumadin) or GP IIb/IIIa antagonists within the preceding 7 days or recent administration of any IV or SC anticoagulation within 12 hours including: unfractionated heparin, enoxaparin, and/or bivalirudin.
  9. Active bleeding, known bleeding diathesis/disorder including thrombocytopenia or clinical diagnosis associated with increased risk of bleeding including: known active peptic ulceration and/or neoplasm with increased bleeding risk.
  10. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current AMI)
  11. Any history of central nervous system abnormality (i.e. neoplasm, aneurysm, intracranial or spinal surgery) or recent trauma to the head or cranium (i.e <3 months)
  12. Any known history of haemorrhagic stroke or stroke of unknown origin
  13. Ischaemic stroke or transient ischaemic attack (TIA) in the preceding 6 months
  14. Prolonged or traumatic cardiopulmonary resuscitation (> 10 minutes) within the past 2 weeks
  15. Known acute pericarditis and/or subacute bacterial endocarditis
  16. Known acute pancreatitis or known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
  17. Chronic dialysis or known renal insufficiency (prior S-creatinine >2.5 mg% (>220 µmol/l) for men and >2.0 mg% (>175 µmol/l)) for women
  18. Pregnancy or lactation or parturition within the previous 30 days; women of childbearing potential must be using a medically accepted method of birth control
  19. Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 7 days
  20. Known hypersensitivity to tenecteplase, alteplase, ASA, clopidogrel, enoxaparin, or to any of the excipients or to the contrast media used in angiography Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk if the investigational therapy is initiated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882635

Locations
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Southlake
NewMarket, Ontario, Canada, l3y 2P9
Sponsors and Collaborators
Robert Welsh
Sanofi
Boehringer Ingelheim
Investigators
Principal Investigator: Robert C Welsh, MD University of Alberta
  More Information

No publications provided

Responsible Party: Robert Welsh, Associate Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT00882635     History of Changes
Other Study ID Numbers: STREAMPCI
Study First Received: April 15, 2009
Last Updated: June 28, 2012
Health Authority: Canada: Biologic and Genetic Therapies Directorate

Keywords provided by University of Alberta:
STEMI
acute coronary syndromes
primary percutaneous coronary intervention

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Calcium heparin
Heparin
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014