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

• Sponsor: Asahi Kasei Pharma America Corporation
• Information provided by (Responsible Party): Asahi Kasei Pharma America Corporation

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Severe Sepsis; Coagulopathy	Drug: ART-123; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 814 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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.
• Actual Study Start Date: October 29, 2012
• Actual Primary Completion Date: April 6, 2018
• Actual Study Completion Date: February 28, 2019

Arms and Interventions

Arm	Intervention/treatment
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 Names: human recombinant thrombomodulin; thrombomodulin alfa
Placebo Comparator: Placebo	Drug: Placebo; Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.

Outcome Measures

Primary Outcome Measures :

1. Primary Efficacy Outcome Measure [ Time Frame: 28 days ]
   28 day all-cause mortality
2. Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
   Adverse Events
3. 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.)
4. Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
   Serious Adverse Events

Secondary Outcome Measures :

1. Secondary Efficacy Outcome Measure [ Time Frame: 3 months ]
   Follow up all-cause mortality at 3 months
2. 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.
3. Secondary Safety Outcome Measure [ Time Frame: 18 months ]
   Presence of Anti-drug antibodies up to 18 months

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

  Show 161 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:

Information on sepsis and treatment 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 19. doi: 10.1001/jama.2019.5358. [Epub ahead of print]

• Responsible Party: Asahi Kasei Pharma America Corporation
• ClinicalTrials.gov Identifier: NCT01598831 History of Changes
• Other Study ID Numbers: 3-001
• First Posted: May 15, 2012
• Last Update Posted: June 19, 2019
• Last Verified: June 2019

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