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Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS) (FUTURA/OASIS 8)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00790907
First received: November 13, 2008
Last updated: June 14, 2012
Last verified: June 2011
  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
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: NCT00790907

  Show 166 Study Locations
Sponsors 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:
Acute Coronary Syndrome
Angina, Unstable
Infarction
Myocardial Infarction
Syndrome
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Disease
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pain
Pathologic Processes
Signs and Symptoms
Vascular Diseases
Calcium heparin
Fondaparinux
Heparin
PENTA
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 November 20, 2014