Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS)
Condition: Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome; Syndrome
Intervention: fondaparinux background and standard dose UFH; Fondaparinux background and low dose heparin; Open label fondaparinux
Intervention description: 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.; 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 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
Intervention MeSH terms: Heparin; PENTA; Fondaparinux
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3235.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Unstable angina; Non ST elevation myocardial infarction; PCI; unfractionated heparin; fondaparinux; acute coronary syndrome

Summary:

      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.
    

Eligibility 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.