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Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Asahi Kasei Pharma America Corporation
Sponsor:
Information provided by (Responsible Party):
Asahi Kasei Pharma America Corporation
ClinicalTrials.gov Identifier:
NCT01598831
First received: May 11, 2012
Last updated: July 14, 2016
Last verified: July 2016
  Purpose
The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.

Condition Intervention Phase
Severe Sepsis
Coagulopathy
Drug: ART-123
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Safety and Efficacy of ART-123 in Subjects With Severe Sepsis and Coagulopathy.

Resource links provided by NLM:


Further study details as provided by Asahi Kasei Pharma America Corporation:

Primary Outcome Measures:
  • Primary Efficacy Outcome Measure [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    28 day all-cause mortality

  • Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ] [ Designated as safety issue: Yes ]
    Adverse Events

  • Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ] [ Designated as safety issue: Yes ]

    Major Bleeding Events defined below will be closely monitored and systematically collected as Serious Adverse Events:

    • any intracranial hemorrhage,
    • any life-threatening bleeding,
    • any bleeding event classified as serious by the Investigator (e.g., resulting in permanent morbidity),
    • or any bleeding that required the administration of 1440 ml (typically 6 units) of packed red cells over two consecutive days.6 (Investigator assessment for seriousness criteria.)

  • Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ] [ Designated as safety issue: Yes ]
    Serious Adverse Events


Secondary Outcome Measures:
  • Secondary Efficacy Outcome Measure [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Follow up all-cause mortality at 3 months

  • Secondary Efficacy Outcome Measure [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Resolution of organ dysfunction as measured through day 28 by shock free, ventilator free, dialysis free plus alive days.

  • Secondary Safety Outcome Measure [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Presence of Anti-drug antibodies up to 18 months


Estimated Enrollment: 800
Study Start Date: August 2012
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ART-123 Drug: ART-123
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days
Other Name: human recombinant thrombomodulin
Placebo Comparator: Placebo Drug: Placebo
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.

Detailed Description:
Study is to evaluate if ART-123 given to patients who have severe sepsis complicated by at least one organ dysfunction and coagulopathy can decrease mortality.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01598831

Contacts
Contact: Scott Oshana 781-419-5039 info@akpamerica.com

  Show 260 Study Locations
Sponsors and Collaborators
Asahi Kasei Pharma America Corporation
Investigators
Study Director: David Fineberg, M.D. Asahi Kasei Pharma America Corporation
  More Information

Additional Information:
Responsible Party: Asahi Kasei Pharma America Corporation
ClinicalTrials.gov Identifier: NCT01598831     History of Changes
Other Study ID Numbers: 3-001 
Study First Received: May 11, 2012
Last Updated: July 14, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Asahi Kasei Pharma America Corporation:
sepsis

Additional relevant MeSH terms:
Sepsis
Toxemia
Blood Coagulation Disorders
Hemostatic Disorders
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on September 26, 2016