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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 4

Conditions: Acute Coronary Syndrome

Treatments: Drug: fondaparinux background and standard dose UFH; Drug: Open label fondaparinux; Drug: Fondaparinux background and low dose heparin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00790907

108888

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3,235 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3,235 participants in 3 patient groups

Open label fondaparinux background and standard dose UFH

Experimental group

Description:

Subjects indicated for PCI and randomized to receive standard dose UFH

Treatment:

Drug: fondaparinux background and standard dose UFH

Open label fondaparinux background and low dose UFH

Experimental group

Description:

Subjects indicated for PCI and randomized to receive low dose UFH

Treatment:

Drug: Fondaparinux background and low dose heparin

Open label fondapaparinux

Other group

Description:

Subjects not indicated for PCI and not randomized

Treatment:

Drug: Open label fondaparinux