Study on Acute blood poisoning due to infection and toxins resulting into bleeding tendencyÂ

Phase 3

• Conditions: Health Condition 1: D758- Other specified diseases of bloodand blood-forming organs

• Registration Number: CTRI/2019/02/017730
• Lead Sponsor: Asahi Kasei Pharma America Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 24 November 2021

Recruitment & Eligibility

• Status: Other (Terminated)
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1.Subjects must be receiving treatment in an ICU or in an acute care setting (e.g. Emergency Room, Recovery Room).

2.Subjects with either compelling evidence of infection OR clinical syndromes highly likely to be bacterial in origin, as follows (Please refer to Appendix B)

a.Compelling objective evidence of bacterial infection and a known site of infection. Objective evidence would be met with a grossly purulent site of infection, Gram stain evidence, culture, rapid immunoassay or genomic based rapid diagnostic assays confirming a bacterial pathogen from normally sterile fluids (blood, urine, cerebrospinal fluid, peritoneal fluid, etc.), having either. White Blood Cell count greater than 12000 per mm3 or less than 4000 per mm3 or greater than 10 percent bands within 36 hours of randomization OR Temperature less than 36 degree Celsius or fever greater than 38 degree Celsius

b.Clinical syndromes highly likely to be bacterial in origin but not compelling White Blood Cell count greater than 12000 per mm3 or less than 4000 per mm3 or greater than 10 percentage bands within 36 hours of randomization AND Temperature less than 36 degree Celsius or fever greater than 38 degree Celsius

3.Current treatment with intravenous antibiotics for the acute bacterial infection (i.e. not prophylactic antibiotics)

4.Subjects with sepsis associated organ dysfunction defined by at least one of the following.

a.Cardiovascular Dysfunction defined as requiring both adequate fluid resuscitation and vasopressors to maintain Mean Arterial Pressure greater than or equal to 65 mmHg with onset time being the time vasopressors are initiated (end of surgery if initiated in surgery), with adequate fluid resuscitation defined as.

Intravenous administration of at least 20 mL per kg crystalloid or 10 mL per kg colloid infusion within 6 hours OR Central Venous Pressure of greater than 8 mmHg or Pulmonary Artery Wedge Pressure of greater than 12 mmHg. If dopamine is the only vasopressor used, the infusion rate must be greater than 5 micro gram per kg per min (i.e., must be prescribed to support cardio-pulmonary perfusion). If vasopressin is used, it must be given in conjunction with another vasopressor.

b. Respiratory Dysfunction defined as the acute need for mechanical ventilation and PaO2 and FiO2 ratio of less than 250 (or less than 200 when lung is the site of infection) with onset time being time of intubation prior to the first qualifying PaO2 and FiO2 ratio (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.

5.Subjects with coagulopathy characterized by an INR greater than 1.40 without other known etiology (e.g., anticoagulant therapy, chronic liver disease), and having an onset at the time of the first blood draw yielding a qualifying result (point of care device INR results must be confirmed by local laboratory).

6.Subjects with coagulopathy characterized by platelet count that meets any of the below criteria, and having an onset at the time of the first blood draw yielding a qualifying result. a. greater than or equal to 20000 per mm3 and less than or equal to 30000 per mm3 that upon retesting after platelet transfusion is greater than 30000 per mm3 (qualifying at the time of the first blood draw yielding a result greater than or equa

Exclusion Criteria

Candidates for the study will be excluded if ANY of the following criteria are present:

1.Subject or Authorized Representative is unable or unwilling to provide informed consent (as applicable per local and country regulations)

2. 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

3. Subject is less than 18 years of age

4.Body weight greater than 175 kg

5.Subject is unwilling to allow transfusion of blood or blood products

6.Presence of an advance directive to withhold life-sustaining treatment (except for Cardiopulmonary Resuscitation), or likely to have life support withdrawn within 24 hours of consent

7.Subject has had previous treatment with ART-123

8.Platelet count less than 20,000 per mm3 for any reason, or for platelet count greater than equal to 20,000 per mm3 and less than 30,000 per mm3 that upon retesting after platelet transfusion does not increase greater than 30,000 per mm3

9.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

10. Inability to randomize patients in less than 12 hours after meeting Inclusion # 7 (onset time requirements for sepsis associated organ dysfunction, INR, and platelet count)

11. < 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). a. 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)

12.Stroke within 3 months prior to consent, trauma or major surgery within 3 months prior to consent that may increase the risk of bleeding

13. Known bleeding diatheses or anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia, esophageal varices, arteriovenous malformation)

14.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

15.Known thrombophilia or a history of deep-vein thrombosis or pulmonary embolism within 3 months prior to consent

16.Need for full dose anticoagulation therapy (other than IV unfractionated heparin discontinued greater than 12 hours prior to randomization), full dose or catheter directed

thrombolysis, aspirin at a daily dose greater than 325 mg, long-acting antiplatelet drugs (eg clopidogrel, prasugrel, or ticagrelor), dual antiplatelet therapy, and doses of anticoagulants exceeding thromboprophylaxis doses within 72 hours prior to the first dose of study drug

17.Acute liver failure not due to sepsis, sepsis associated ac

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Safety Endpoints: <br/ ><br>â?¢ Serious Adverse Events <br/ ><br>â?¢ Major Bleeding Events <br/ ><br>â?¢ Adverse EventsTimepoint: Through 28-day (Day 29) all-cause mortality <br/ ><br> <br/ ><br>â?¢ Major Bleeding Events <br/ ><br>â?¢ Adverse Events

Secondary Outcome Measures

Name	Time	Method
â?¢ Resolution of Organ Dysfunction through Day 28 as measured by <br/ ><br>o Shock free and alive days <br/ ><br>o Ventilator free and alive days <br/ ><br>o Dialysis free and alive days <br/ ><br>Secondary Safety Endpoint: <br/ ><br>â?¢ Anti-drug antibodies (ADA) to ART-123Timepoint: â?¢ Follow-up of all-cause mortality at 3 months