Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy
Condition: Severe Sepsis; Coagulopathy
MeSH terms: Sepsis; Toxemia; Hemostatic Disorders; Blood Coagulation Disorders
Intervention: ART-123; Placebo
Intervention description: Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days; Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 816.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: sepsis

Summary:

      The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis
      can decrease mortality.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER,
             RR)

          -  Clinical objective evidence of bacterial infection and a known site of infection.

          -  Cardiovascular dysfunction or Respiratory Failure due to sepsis.

          -  Coagulopathy characterized by an INR >1.40 without other known causes.

        Exclusion Criteria:

          -  Subject or Authorized Representative is unable to provide informed consent.

          -  Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of
             enrolling into the study.

          -  Subject is of childbearing potential and does not have a negative pregnancy test.

          -  Subject is < 18 years of age.

          -  Subject has a known allergy to ART-123 or any components of the drug product.

          -  Subject is unwilling to allow transfusion of blood or blood products.

          -  Subject has an advance directive to withhold life-sustaining treatment.

          -  Subject has had previous treatment with ART-123.

          -  Body weight ≥ 175 kg.

          -  Platelets < 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is
             not due to sepsis.

          -  Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or
             non-traumatic orthopedic surgery of the femur or pelvis) that is completed within 12
             hours prior to first dose of study drug, or ongoing impairment of hemostasis as a
             result of one of these procedures

          -  History of head trauma, spinal trauma, or other acute trauma with an increased risk of
             bleeding within 3 months prior to consent.

          -  Cerebral Vascular Accident (CVA) within 3 months prior to consent.

          -  Any history of intracerebral arteriovenous malformation (AVM), cerebral aneurysm, or
             mass lesions of the central nervous system.

          -  History of congenital bleeding diathesesor anatomical anomaly that predisposes to
             hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia).

          -  Significant gastrointestinal bleeding within 6 weeks prior to consent.

          -  Subject is diagnosed with a known medical condition associated with a hypercoagulable
             state.

          -  Child-Pugh score of 10-15 (Class C)

          -  Portosystemic hypertension or known history of bleeding esophageal varices.

          -  History of solid organ, allogeneic bone marrow, or stem cell transplantation within
             the 6 months prior to consent.

          -  Acute pancreatitis where infection has not been documented by a positive blood or
             abdominal fluid culture or gram stain consistent with bacterial infection.

          -  Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal
             replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine
             output < 0.3 ml/kg/hr) > 48 hours prior to first dose of study drug whether receiving
             RRT or not

          -  Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within
             the 72 hours prior to first does of study drug.

          -  Life expectancy < 90 days.

          -  Current use of any chemotherapy agent likely to cause myeloablation (severe or
             complete depletion of bone marrow).

          -  Participation in another research study involving an investigational agent within 30
             days prior to consent or projected study participation during the 28 days post study
             randomization.

          -  Confirmed or suspected endocarditis