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 February 2014 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: February 3, 2014
Last verified: February 2014
  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 as:

    • any intracranial hemorrhage, (Qualifies as a Serious Adverse Event)
    • any life-threatening bleeding, (Qualifies as a Serious Adverse Event)
    • any bleeding event classified as serious by the Investigator (e.g., resulting in permanent morbidity), (Qualifies as a Serious Adverse Event)
    • or any bleeding that required the administration of 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: March 2016
Estimated Primary Completion Date: March 2015 (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
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 with orders to transfer to ICU.
  • Clinical 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.
  • PT prolongation or thrombocytopenia that is not due to sepsis.
  • Intra-thoracic or intra-abdominal surgery within 12 hours prior to consent, or ongoing bleeding issues 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 diatheses.
  • 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.
  • Severe renal failure requiring chronic or acute need of hemodialysis, hemofiltration or peritoneal dialysis.
  • Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to consent.
  • 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.
  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: Matt Mockler 781-419-1919 info@akpamerica.com

  Show 187 Study Locations
Sponsors and Collaborators
Asahi Kasei Pharma America Corporation
Investigators
Study Director: Inder Kaul, M.D., MPH Asahi Kasei Pharma America Corporation
  More Information

Additional Information:
No publications provided

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: February 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Asahi Kasei Pharma America Corporation:
sepsis

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

ClinicalTrials.gov processed this record on August 20, 2014