TUESDAY 19TH OCTOBER2010 CATH LAB PRESENTATION. TAO /ACS study STUDY NUMBER: EFC6204 Randomized,...
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Transcript of TUESDAY 19TH OCTOBER2010 CATH LAB PRESENTATION. TAO /ACS study STUDY NUMBER: EFC6204 Randomized,...
TUESDAY 19TH OCTOBER2010
CATH LAB PRESENTATION
TAO /ACS study
STUDY NUMBER: EFC6204
Randomized, double-blind, triple-dummy trial to compare the efficacy of otamixaban with Unfractionated Heparin + eptifibatide, in patients with Unstable angina/Non ST segment Elevation Myocardial infarction scheduled to undergo an early invasive strategy
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Inclusion Criteria
• Patient with non-STE-ACS with ischemic discomfort (ie, ischemic chest pain or equivalent) at rest ≥10 minutes within 24 hours of randomization
and• One of the two following criteria of non-ST elevation ACS:
• New ST-segment depression ≥0.1 mV (≥1 mm), or transient (<30 minutes) ST-segment elevation ≥0.1 mV (≥1 mm) in at least 2 contiguous leads on the ECG,
OR • Elevation of cardiac biomarkers within 24 hours of randomization,
defined as elevated troponin T, troponin I, or CK-MB level above upper limit of normal
and• Planned to have a coronary angiography (followed, when
indicated, by PCI) as early as possible (after at least 2 hours of treatment with study drug) and within 36 hours (at the latest on Day 3, if justified)
and• Informed consent obtained in writing
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Exclusion Criteria
Related to prior or concomitant treatments
Patient having received anticoagulant treatment (including UFH, LMWH, or bivalirudin) for more than 24 hours prior to randomization or who have been treated by fondaparinux or abciximab
Inability to discontinue current anticoagulation in order to transition to Investigational Products according to the specified transition timing
Patients who can not be treated by aspirin and clopidogrel (or any other oral antiplatelet agent) according to their local labeling
Exclusion criteria
Related to eptifibatide
Patient who cannot be treated with eptifibatide according to the national labeling
Related to unfractionated heparin
Patient who cannot be treated with UFH according to the national labeling
Related to otamixaban
Allergy to otamixaban
Otamixaban Characteristics
Specific Factor Xa inhibitor Proximal inhibition of the coagulation cascade
Small molecule, direct inhibitor Allows for inhibition of clot-bound factor Xa, which
is inaccessible to large molecule and indirect inhibitors
Reversible, short initial half-life (20-30 mins) Given as wt-based IV bolus & infusion Eliminated via feces/bile, no significant renal
elimination Permits rapid initiation & d/c of anticoagulation
Discontinued prior anticoagulants
R
IVRS
Signature of ICF
Preparation of study drugs
Administration of study drugs
Transition Timing for Discontinuation of Previous Anticoagulation
Delay between discontinuation open label anticoagulant and study drug:
UFH or bivaluridin 90 - 150 minutes (unless aPTT < 50 sec)
LMWH 8 hours since last injection
Tirofiban or eptifibatide 4 hours
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Triple Dummy Design
Randomized to Otamixaban
OtamixabanPlacebo
UFHPlacebo
Eptifibatide
Randomized to UFH + Eptifibatide
PlaceboOtamixaban
UFH Eptifibatide
Otamixaban/pbo ; UFH/pbo ; and Eptifibatide/pbo
prepared by Pharmacist or Investigator using
study kits
PCI startPCI start
Study Drug Administration A9
If no PCI is performed
Drug A
Drug B: monitoring of APTT (blinded) pre PCI and during PCI: target 1.5-2XN
Randomization
ASA, Clopi , other ADP receptor antagonistAs per label and guidelines
CK MB and Troponin T (or I) : at 8h and 16h post Randomization
Per investigator’s judgment Up to Day 4 maximum
PCI
Drug A
Drug B: monitoring of ACT (blinded) pre PCI and during PCI: target > 200s
Pre PCI PCI start
ASA, Clopi , other ADP receptor antagonistAs per label and guidelines
CK MB and Troponin T (or I) : Pre PCI and at 2h, 8h and 16h post PCI
PCI end
ACT for sheath removal
After PCI
Drug C started immediately before PCI start and continued up to 18-24h post PCI or until hospital discharge
• Within 36h (if possible, 2 hrs after start of study meds), max Day 3 if justified
• Open-label UFH flushes per operator ++++++++• Bail-out eptifibatide if severe Recurrent Ischemia or thromb PCI
complication
TAO /ACS study
Flushing of the catheter with UF : During coronary angiography/PCI: the catheters
must be flushed with heparinized serum saline.
Thrombotic complications during PCI/angio: Consider bailout with eptifibatide (+ check ACT
and give additional Drug B bolus if <225s)
BLINDED ACT / Hemochron Device
Direct Venous Blood Sample• Cannot use “finger sticks”• CAN use “buff caps/heplocks/IV starts”• MUST be downstream from study drug infusion site
Consider femoral vein sheath
Clinical Challenges