The Safety And Efficacy of ART-123 in Subjects With Sepsis and Coagulopathy

NCT03517501 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: AKPA 3-3002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Sepsis and Coagulopathy

Outcome Measures

Primary Outcomes (1)

• 28 day

  All-cause mortality

  28 days

Secondary Outcomes (5)

• 3 months

  3 months

• Resolution of organ dysfunction through 28 days as measured by:

  28 days

• Resolution of organ dysfunction through 28 days as measured by:

  28 days

• Resolution of organ dysfunction through 28 days as measured by:

  28 days

• 6 and 12 months

  6 or 12 months

Study Arms (2)

ART-123

ACTIVE COMPARATOR

Drug: ART-123

Placebo

PLACEBO COMPARATOR

Drug: Placebo Comparator - Placebo

Interventions

ART-123 DRUG

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

Also known as: human recombinant thrombomodulin

ART-123

Placebo Comparator - Placebo DRUG

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be receiving treatment in an ICU or in an acute care setting (e.g., Emergency Room, Recovery Room).
• Subjects with either compelling evidence of infection OR clinical syndromes highly likely to be bacterial in origin, as follows (Please refer to Appendix B):
• Compelling objective evidence of bacterial infection and a known site of infection: Objective evidence would be met with a grossly purulent site of infections, Gram stain evidence, confirming a bacterial pathogen from normally sterile fluids (blood, urine, cerebrospinal fluid (CSF), peritoneal fluid, etc.), having either:
• White Blood Cell (WBC) count greater \> 12,000/mm3 or \< 4,000/mm3 or \> 10% bands within 36 hours of randomization OR
• Temperature \<36°C or fever \>38°C
• Clinical syndromes highly likely to be bacterial in origin but not compelling
• White Blood Cell (WBC) count greater \> 12,000/mm3 or \< 4,000/mm3 or \> 10% bands within 36 hours of randomization AND
• Temperature \<36°C or fever \>38°C
• Current treatment with intravenous antibiotics for the acute bacterial infection (i.e. not prophylactic antibiotics)
• Subjects with sepsis-associated organ dysfunction defined by at least one of the following:
• Cardiovascular Dysfunction defined as requiring both adequate fluid resuscitation and vasopressors\* to maintain Mean Arterial Pressure (MAP) greater than or equal to (≥) 65 mmHg (implies fluid resuscitation alone does not raise MAP to ≥ 65 mmHg), with onset time being the time of vasopressors are initiated (end of surgery if initiated in surgery), with adequate fluid resuscitation defined as:
• Intravenous administration of at least 20 mL/kg crystalloid or 10 mL/kg colloid infusion within 6 hours.
• Central Venous Pressure (CVP) of greater than (\>) 8 mmHg or Pulmonary Artery Wedge Pressure (PAWP) of greater than (\>) 12 mmHg.
• If dopamine is the only vasopressor used, the infusion rate must be greater than (\>) 5 μg/kg/min (i.e., must be prescribed to support cardio-pulmonary perfusion). If vasopressin is used, it must be given in conjunction with another vasopressor.
• Respiratory Dysfunction is defined as the acute need for mechanical ventilation and PaO2/FiO2 ratio of \<250 (or \< 200 when lung is the site of infection) with onset time being time of intubation prior to first qualifying PaO2:FiO2 (if intubated for surgery and unable to extubate the qualifying time is the end of surgery), with mechanical ventilation defined as any type of ventilation administered via an endotracheal or nasotracheal tube.

You may not qualify if:

• Candidates for the study will be excluded if ANY of the following criteria are present:
• Subject or Authorized Representative is unable or unwilling to provide informed consent (as applicable per local and country regulations)
• Subject is pregnant (positive serum or urine human Chorionic Gonadotropin (hCG)) or breastfeeding or intends to get pregnant within 28 days of enrolling into the study
• Subject is \< 18 years of age
• Body weight ≥ 175 kg
• Subject is unwilling to allow transfusion of blood or blood products
• Presence of an advance directive to withhold life-sustaining treatment (except Cardiopulmonary Resuscitation), or likely to have life support withdrawn within 24 hours of consent
• Subject has had previous treatment with ART-123
• Platelet count \< 20,000/ mm3 for any reason, or for platelet count ≥ 20,000/mm3 and ≤ 30,000/mm3 that upon retesting after platelet transfusion does not increase \> 30,000/mm3
• Elevated INR, leukopenia, or thrombocytopenia that is not due to sepsis, (e.g. patients treated by chemotherapy agent). Please refer to Appendix C as an example of agents known to cause myelosuppression that should be evaluated as the cause of potential leukopenia or thrombocytopenia
• ≤ 8 hours remaining from the end of a major surgery having a high risk of post-operative bleeding and randomization (e.g. extensive intraabdominal or intrathoracic dissection, debridement of a large surface area of tissue, complications arising during surgery, problems with hemostasis during surgery, surgeries of long duration, surgeries with large estimated blood loss).
• Ensures all randomized surgical subjects with a high risk of post-operative bleeding can be dosed no earlier than 12 hours post-operatively, as described in Section 2.6.3. (minimum 8 hour delay before randomization and 4 hour maximum time to dose after randomization)
• Stroke within 3 months prior to consent, trauma or major surgery within 3 months prior to consent that may increase the risk of bleeding
• Known bleeding diatheses or anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia, esophageal varices, arteriovenous malformation)
• Gastrointestinal bleeding (e.g., melena, hematemesis) or genitourinary bleeding within 6 weeks prior to consent unless a corrective interventional procedure has been performed (i.e., therapeutic endoscopy), or there is evidence of complete resolution

Sponsors & Collaborators

• Asahi Kasei Pharma America Corporation: lead

MeSH Terms

Conditions

Sepsis; Hemostatic Disorders

Interventions

ART123

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• David Fineberg, MD

  Asahi Kasei Pharma America

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 7, 2018
• Study Start: July 1, 2019
• Primary Completion: April 1, 2022
• Study Completion: May 1, 2023
• Last Updated: September 13, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share