Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS) (FUTURA/OASIS 8)
This study has been completed.
Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00790907
First received: November 13, 2008
Last updated: June 14, 2012
Last verified: June 2011
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Purpose
The purpose of this study is to compare the safety of two different dose regimens of unfractionated heparin (UFH) during a percutaneous coronary intervention (PCI) procedure in patients with UA (unstable angina)/NSTEMI (non ST segment elevation myocardial infarction) who have been initially treated with fondaparinux.
| Condition | Intervention | Phase |
|---|---|---|
|
Unstable Angina Non ST Segment Elevation Myocardial Infarction |
Drug: fondaparinux background and standard dose UFH Drug: Fondaparinux background and low dose heparin Drug: Open label fondaparinux |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | FondaparinUx Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS) (FUTURA). A Prospective Study Evaluating the Safety of Two Regimens of Adjunctive Intravenous UFH During PCI in High Risk Patients With Unstable Angina/Non ST Segment Elevation Myocardial Infarction (UA/NSTEMI) Initially Treated With Subcutaneous Fondaparinux and Referred for Early Coronary Angiography (OASIS 8) |
Resource links provided by NLM:
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
- Number of Participants With Composite of Major Bleeding, Minor Bleeding, or Major Vascular Access Site Complications During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ] [ Designated as safety issue: Yes ]The peri-percutaneous coronary intervention (peri-PCI) period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major and minor bleeding events were adjudicated by a blinded central independent adjudication committee (CIAC). Major vascular access site complications comprised large hematoma, pseudoaneurysm requiring treatment, aterio-venous fistula, or other vascular procedures related to the access site.
Secondary Outcome Measures:
- Number of Participants With Composite of Major Bleeding During the Peri-PCI Period, With Death, MI, or TVR at Day 30 [ Time Frame: Peri-PCI period for major bleeding (during the time from randomization up to 48 hours after the end of PCI [typically 49 hours total] ) and from randomization up to Day 30 for death, MI, or TVR ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of death, myocardial infarction (MI) and target vessel revascularisation (TVR) was performed at Day 30. Major bleeding, MI and TVR were adjudicated by a blinded CIAC.
- Number of Participants With Major Bleeding During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major bleeding, MI and TVR were adjudicated by a blinded CIAC.
- Number of Participants With Minor Bleeding During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Minor bleeding events were adjudicated by a blinded CIAC.
- Number of Participants With Major Vascular Access Site Complications During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major vascular access site complications included: large hematoma, pseudoaneurysm requiring treatment, arterio-venous fistula, or other vascular procedures related to the access site.
- Number of Participants With Major PCI-related Procedural Complications [ Time Frame: During PCI procedure: immediately after randomization (approximately 10-75 minutes) ] [ Designated as safety issue: Yes ]Major PCI-related procedural complications included: abrupt vessel closure, a new angiographic filling defect representing either angiographic thrombus or major dissection with reduced flow, no-reflow phenomenon, or catheter-related thrombus. Investigator reports of catheter-related thrombus were defined as suspected catheter-related thrombus events, and were adjudicated by a blinded CIAC.
- Number of Participants With Composite of Death, MI or TVR During the Peri-PCI Period and at Day 30 [ Time Frame: Peri-PCI (during the time from randomization up to 48 hours after the end of PCI, typically 49 hours total) and from randomization up to Day 30 ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of composite of death, MI, or TVR was performed both during the peri-PCI period and at Day 30. MI and TVR events were adjudicated by a blinded CIAC.
- Number of Participants Experiencing Death, MI, TVR, Definite/Probable Stent Thrombosis, or Stroke, Assessed Separately During the Peri-PCI Period and at Day 30 [ Time Frame: Peri-PCI (during the time from randomization up to 48 hours after the end of PCI, typically 49 hours total) and from randomization up to Day 30 ] [ Designated as safety issue: Yes ]The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of death, MI, TVR, definite/probable stent thrombosis, or stroke was performed during the peri-PCI period and at Day 30. MI, TVR, definite/probable stent thrombosis, and stroke events were adjudicated by a blinded CIAC.
| Enrollment: | 3235 |
| Study Start Date: | February 2009 |
| Study Completion Date: | May 2010 |
| Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Open label fondaparinux background and standard dose UFH
Subjects indicated for PCI and randomized to receive standard dose UFH
|
Drug: fondaparinux background and standard dose UFH
Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded standard dose UFH (based on planned glycoprotein [GP] IIb/IIIa inhibitor use: 60 units/kilogram (U/kg); no planned use: 85 U/kg and adjusted based on activated clotting time (ACT) [maximum two additional bolus doses]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.
|
|
Experimental: Open label fondaparinux background and low dose UFH
Subjects indicated for PCI and randomized to receive low dose UFH
|
Drug: Fondaparinux background and low dose heparin
Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded low-dose UFH (50 U/kg), which was not adjusted for planned GPIIb/IIIa inhibitor use or ACT). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.
|
|
Open label fondapaparinux
Subjects not indicated for PCI and not randomized
|
Drug: Open label fondaparinux
Open-label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier, for those participants not indicated for PCI and not randomized
|
Detailed Description:
Subjects presenting at hospital with suspected UA or NSTEMI and who are likely to undergo angiography (ideally within 72 hours) will be assessed for eligibility and consented. Suitable subjects will be enrolled and commence treatment with open-label fondaparinux, 2.5 milligram (mg), subcutaneous (s.c.), once daily. Following angiography subjects indicated for PCI and meeting the additional requirements for randomization will be randomised to receive one of two dose regimens of UFH either standard dose or low dose immediately prior to the PCI procedure. Post-PCI, therapy with fondaparinux (2.5 mg, s.c.) may be resumed at the investigator's discretion for up to a maximum of 8 days or hospital discharge, whichever is earlier.
Subjects not indicated for PCI, will continue treatment with fondaparinux, 2.5mg, s.c, once daily for up to 8 days or hospital discharge, whichever is earlier.
All subjects will be followed up for 30 days after randomization/angiography.
Eligibility| Ages Eligible for Study: | 21 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
The following are inclusion and exclusion criteria for enrollment in the study:
Inclusion Criteria:
- Presenting or admitted to hospital with symptoms suspected to represent UA or NSTEMI, i.e., clinical history consistent with new onset, or a worsening pattern of, characteristic ischemic chest pain or ischemic symptoms occurring at rest or with minimal activity (lasting longer than 5 minutes or requiring sublingual nitro-glycerine for relief of the pain).
- Available to be enrolled within 48 hours of the onset of the most recent episode of symptoms.
- Planned coronary angiography, with PCI if indicated, within 72 hours of enrollment where possible.
- At least two of the three following additional criteria:
- Age greater than or equal to 60 years
- Troponin T or I or CK-MB above the upper limit of normal for the local institution;
- Electrocardiogram (ECG) changes compatible with ischemia, i.e., ST depression at least 1 mm in 2 contiguous leads or T wave inversion > 3 mm or any dynamic ST shift or transient ST elevation.
- Written informed consent dated and signed
Exclusion Criteria:
- Age < 21 years.
- Any contraindication to UFH or fondaparinux
- Contraindication for angiography or PCI at baseline
- Subjects requiring urgent (<120 minutes) coronary angiography as characterized by those with:
- refractory or recurrent angina associated with dynamic ST-deviation
- heart failure
- life-threatening arrhythmias
- hemodynamic instability
- Subjects already receiving treatment with enoxaparin (or other LMWH), bivalirudin or UFH for treatment of the qualifying events unless the last administered (intravenous(i.v.) or s.c.) dose was:
- ≥ 8 hours for low molecular weight heparin (LMWH)
- ≥60 minutes for bivalirudin
- ≥90 minutes for unfractionated heparin (UFH)
- Hemorrhagic stroke within the last 12 months.
- Indication for anti-coagulation other than acute coronary syndrome (ACS) during the index hospitalization.
- Pregnancy or women of childbearing potential who are not using an effective method of contraception.
- Co-morbid condition with life expectancy less than 6 months.
- Currently receiving an experimental pharmacological agent.
- Revascularization procedure already performed for the qualifying event.
- Severe renal insufficiency (i.e., estimated creatinine clearance <20 ml/min)
Following angiography and confirmation that the subject is to undergo PCI, the subject must also meet all of the following additional criteria in order to be randomised:
- Subjects will have received at least 1 dose of open-label fondaparinux
- The most recent dose of open-label fondaparinux will not have been more than 24 hours before the start of the PCI procedure.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00790907
Show 166 Study Locations
Show 166 Study LocationsSponsors and Collaborators
GlaxoSmithKline
Investigators
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
More Information
Publications:
The FUTURA/OASIS-8 Trial Group. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux. The FUTURA/OASIS-8 randomized trial. JAMA. 2010; 304(12):1339-1349.
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT00790907 History of Changes |
| Other Study ID Numbers: | 108888 |
| Study First Received: | November 13, 2008 |
| Results First Received: | May 10, 2011 |
| Last Updated: | June 14, 2012 |
| Health Authority: | Japan: Ministry of Health, Labor and Welfare United Kingdom: Medicines and Healthcare Products Regulatory Agency Argentina: Ministry of Health - A.N.M.A.T Brazil: ANVISA Russia: Russian Ministry of Health Canada: Health Canada India: Drugs Controlle Gerneral of India South Korea: Food and Drug Administration United States: Food and Drug Administration Europe: European Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by GlaxoSmithKline:
|
Unstable angina Non ST elevation myocardial infarction PCI |
unfractionated heparin fondaparinux acute coronary syndrome |
Additional relevant MeSH terms:
|
Angina Pectoris Angina, Unstable Infarction Myocardial Infarction Acute Coronary Syndrome Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Chest Pain Pain Signs and Symptoms Ischemia Pathologic Processes |
Necrosis Calcium heparin Fondaparinux PENTA Heparin Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents |
ClinicalTrials.gov processed this record on June 13, 2013