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

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ClinicalTrials.gov Identifier: NCT01598831
Recruitment Status : Completed
First Posted : May 15, 2012
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Asahi Kasei Pharma America Corporation

Tracking Information
First Submitted Date  ICMJE May 11, 2012
First Posted Date  ICMJE May 15, 2012
Last Update Posted Date June 19, 2019
Actual Study Start Date  ICMJE October 29, 2012
Actual Primary Completion Date April 6, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
  • Primary Efficacy Outcome Measure [ Time Frame: 28 days ]
    28 day all-cause mortality
  • Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
    Adverse Events
  • Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
    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 ]
    Serious Adverse Events
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2012)
  • Primary Efficacy Outcome Measure [ Time Frame: 28 days ]
    28 day all-cause mortality
  • Primary Safety Outcome Measure [ Time Frame: 28 days ]
    Serious Adverse Events
  • Primary Safety Outcome Measure [ Time Frame: 28 days ]
    Major bleeding events
  • Primary Safety Outcome Measure [ Time Frame: 28 Days ]
    Adverse events
Change History Complete list of historical versions of study NCT01598831 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2012)
  • Secondary Efficacy Outcome Measure [ Time Frame: 3 months ]
    Follow up all-cause mortality at 3 months
  • Secondary Efficacy Outcome Measure [ Time Frame: 28 days ]
    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 ]
    Presence of Anti-drug antibodies up to 18 months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy
Official Title  ICMJE 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.
Brief Summary The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Sepsis
  • Coagulopathy
Intervention  ICMJE
  • Drug: ART-123
    Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days
    Other Names:
    • human recombinant thrombomodulin
    • thrombomodulin alfa
  • Drug: Placebo
    Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.
Study Arms  ICMJE
  • Active Comparator: ART-123
    Intervention: Drug: ART-123
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Vincent JL, Francois B, Zabolotskikh I, Daga MK, Lascarrou JB, Kirov MY, Pettilä V, Wittebole X, Meziani F, Mercier E, Lobo SM, Barie PS, Crowther M, Esmon CT, Fareed J, Gando S, Gorelick KJ, Levi M, Mira JP, Opal SM, Parrillo J, Russell JA, Saito H, Tsuruta K, Sakai T, Fineberg D; SCARLET Trial Group. Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA. 2019 May 28;321(20):1993-2002. doi: 10.1001/jama.2019.5358.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 22, 2018)
814
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2012)
800
Actual Study Completion Date  ICMJE February 28, 2019
Actual Primary Completion Date April 6, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Croatia,   Czechia,   Finland,   France,   Germany,   Hungary,   India,   Israel,   Korea, Republic of,   Netherlands,   New Zealand,   Peru,   Russian Federation,   Serbia,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Colombia,   Czech Republic,   Greece,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01598831
Other Study ID Numbers  ICMJE 3-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Asahi Kasei Pharma America Corporation
Study Sponsor  ICMJE Asahi Kasei Pharma America Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Fineberg, M.D. Asahi Kasei Pharma America Corporation
PRS Account Asahi Kasei Pharma America Corporation
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP