Anticoagulation With rNAPc2 to Eliminate MACE/TIMI 32

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The primary focus of this study is to explore the safety of a range of doses of rNAPc2 in subjects who are managed in hospitals that most typically practice an early invasive strategy (catheterization during the index admission). After completion of the ascending dose-ranging part of the trial and review of these data by the Data and Safety Monitoring Board (DSMB), the maximum tolerated dose of rNAPc2 will be studied in single-arm, open-label panels (approximately 25 subjects each) of rNAPc2 with descending doses of unfractionated heparin (UFH).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ARCA Biopharma, Inc.
• Collaborator: The TIMI Study Group
• Treatments: Anticoagulants; Protein C; Thromboplastin

Criteria

Inclusion Criteria:

• Ages 18 to 75 years inclusive

• Ischemic symptoms lasting >= 5 minutes at rest within the prior 48 hours

• Able to be randomized within 48 hours of recent ischemic events

• At least one of the following criteria (A, B, or C): A. Elevation of CK-MB or troponin above upper limit of normal OR B. ST segment deviation (depression or transient elevation) of at least 0.5 mm OR C. TIMI risk score >= 3, defined as three or more of the following:

• Age >= 65;

• At least 3 of the following risk factors: hypertension, diabetes mellitus, current smoker (within 1 year), dyslipidemia, family history of premature coronary artery disease (< age 60);

• Known or prior coronary artery stenosis > 50%;

• Daily aspirin use for at least 7 days;

• >= 2 ischemic episodes at rest lasting >= 15 minutes each within the prior 24 hours;

• Elevation of CK-MB OR troponin above upper limit of normal;

• ST segment deviation (depression or transient elevation) of at least 0.5 mm.

• Ability to understand and willingness to give written informed consent

• Planned early invasive strategy in the index hospitalization

Exclusion Criteria:

• Index event is ST-segment elevation MI or new LBBB

• CABG is planned within 7 days

• ACS is secondary to non-atherosclerotic mechanism (e.g. thyrotoxicosis, anemia)

• Prior participation in ANTHEM-TIMI 32, prior exposure to rNAPc2, or participation in a study with any experimental drug or device within 30 days

• Pregnancy, lactation or use of an intrauterine device (note: women of childbearing potential must have a negative b-HCG)

• Active renal disease, Cr > 4 mg/dl, or history of renal transplantation

• History of a bleeding diathesis or recurrent bleeding episodes

• Medical comorbidities which place subject at risk for hemorrhage, including, but not limited to, prior cerebral hemorrhage, arteriovenous malformation, non-hemorrhagic CVA or TIA, GI bleed, active PUD, advanced liver or renal disease. Major trauma, surgery, CNS, spinal or eye surgery within 6 months, or parenchymal organ biopsy within 14 days.

• Uncontrolled hypertension (SBP > 180, DBP > 100) despite 1 hour of adequate treatment

• Gross hematuria within 1 month unless catheterized and subsequently resolved

• Chronic warfarin (INR > 1.4) or anticipated therapy for warfarin

• Platelet count < 120,000/mm3 at randomization or history of thrombocytopenia (confirm in a blue-top tube using sodium citrate)

• Significant anemia (M: Hg < 11 g/dL, F: Hg < 10 g/dL) at randomization

• Active liver disease or ALT and AST > 3 x ULN not felt to be part of presenting ACS

• Fibrinolytic agent within 24 hours or planned use of fibrinolytics

• Known allergy or intolerance to aspirin

• Known allergy to heparin, enoxaparin or pork-based products

• History of heparin-induced thrombocytopenia (type 1 or 2)

• Any condition for which the investigator feels enrollment in the study would place the subject at unacceptable risk (e.g. substance abuse)

• Part 2 ONLY: Use of LMWH or Xa inhibitor (e.g. Angiomax, Argatroban) >= 12 hours before randomization