Acute Myocardial InfarctionPhase 3NCT00882635
The STREAM Percutaneous Coronary Intervention Anticoagulant Sub-study
A Phase 3 study testing enoxaparin and Unfractionated heparin in people with Acute Myocardial Infarction, run by Robert Welsh at 2 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myocardial Infarction
- What is being tested?
- enoxaparin and Unfractionated heparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 2 sitesCanada
- Study dates
- Oct 2008to Jun 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age equal or greater than 18 years
- Onset of symptoms of STEMI < 3 hours prior to randomisation
- 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.
- Informed consent received
Who cannot join
- 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.
- Anticipated or obvious problem with vascular access.
- Previous CABG
- Left bundle branch block or ventricular pacing.
- Patients with cardiogenic shock - Killip Class 4
- Patients with a body weight < 55 kg (known or estimated)
Show all 20Show fewer
- 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.
- 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.
- 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.
- Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current AMI)
- 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)
- Any known history of haemorrhagic stroke or stroke of unknown origin
- Ischaemic stroke or transient ischaemic attack (TIA) in the preceding 6 months
- Prolonged or traumatic cardiopulmonary resuscitation (> 10 minutes) within the past 2 weeks
- Known acute pericarditis and/or subacute bacterial endocarditis
- Known acute pancreatitis or known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
- 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
- Pregnancy or lactation or parturition within the previous 30 days; women of childbearing potential must be using a medically accepted method of birth control
- Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 7 days
- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Southlake
Newmarket, Ontario, l3y 2P9
About this study
Official title: The STrategic Reperfusion Early After Myocardial Infarction (STREAM) Anticoagulation With Enoxaparin vs. Unfractionated Heparin in Primary PCI Sub-study.
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.
Read the 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.
- Conditions
- Acute Myocardial Infarction
- Being tested
- enoxaparin, Unfractionated heparin
- Keywords
- STEMI, acute coronary syndromes, primary percutaneous coronary intervention
- Medical subject headings
- ST Elevation Myocardial Infarction, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enoxaparinDrug
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
Unfractionated heparinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Enoxaparin | Experimental | Not described Receives: Drug: enoxaparin |
| Unfractionated heparin | Active comparator | Not described Receives: Drug: Unfractionated heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: During Primary PCI
Secondary outcomes (2)
Composite of major bleeding (non-CABG), death, cardiogenic shock, and congestive heart failure
Measured: 30 days
ECG & angiographic measures before and after primary PCI
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2009 (estimated)
- Study startOct 2008
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert Welsh
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, Boehringer Ingelheim
- Responsible party
- Sponsor-investigator, Robert Welsh, University of Alberta
- Investigators
- Robert C Welsh, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00882635
- Sponsor's protocol ID
- STREAMPCI
- Status last verified
- Jun 2012
- First submitted
- 15 Apr 2009
- Last updated
- 2 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The STrategic Reperfusion Early After Myocardial Infarction (STREAM) Anticoagulation With Enoxaparin vs. Unfractionated Heparin in Primary PCI Sub-study.
- ClinicalTrials.gov ID
- NCT00882635
- Acronym / sponsor ID
- STREAMPCI
- Conditions
- Acute Myocardial Infarction
- Keywords
- STEMI, acute coronary syndromes, primary percutaneous coronary intervention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Robert WelshUniversity, hospital or other
- Collaborators
- Sanofi, Boehringer Ingelheim
- Study start
- Oct 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 16 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enoxaparin | Experimental | Drug: enoxaparin |
| Unfractionated heparin | Active comparator | Drug: Unfractionated heparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age equal or greater than 18 years
- Onset of symptoms of STEMI < 3 hours prior to randomisation
- 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.
- Informed consent received
Key exclusion criteria (20 listed)
- 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.
- Anticipated or obvious problem with vascular access.
- Previous CABG
- Left bundle branch block or ventricular pacing.
- Patients with cardiogenic shock - Killip Class 4
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enoxaparinEnoxaparin 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 | Drug | Enoxaparin |
| Unfractionated heparinUnfractionated 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 | Drug | Unfractionated heparin |
Primary outcome
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
2 secondary outcomes
Composite of major bleeding (non-CABG), death, cardiogenic shock, and congestive heart failure
Time frame: 30 days
ECG & angiographic measures before and after primary PCI
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert C Welsh, MD principal investigator
University of Alberta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing enoxaparin and Unfractionated heparin in people with Acute Myocardial Infarction, run by Robert Welsh at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2012.