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

Phase 3

Completed

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

• Registration Number: CTRI/2013/09/003995
• Lead Sponsor: Asahi Kasei Pharma America Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2019-02-21
• Last Update Posted: 24 November 2021

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 86

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 a. Clinical objective evidence of bacterial infection and a known site of infection. b. Current treatment with intravenous antibiotics.c. White Blood Cell (WBC) count greater than 12,000 per mm3 or less than 4,000 per mm3 or Bandemia greater than 10percent. d. Temperature of less than 36 degree centrigrade or fever greater than 38 degree centigrade. For hypothermia, a core reading is preferred. Note 1 If a subject has a Gram stain consistent with bacterial infection, positive culture from blood or an otherwise sterile body fluid, observed peritonitis, positive urinary antigen, clinical presentation of meningococcemia, or otherwise compelling evidence of infection as determined by the CCC, only one of the two inclusion criteria 2c (WBC) or 2d (temperature) is required. Note 2 The presence of concurrent fungal or viral infection is allowed for the study entry, provided that the primary reason for treatment is bacterial infection.

3. 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 (MAP) greater than or equal to 65 mmHg (implies fluid resuscitation alone does not raise MAP to greater than 65 mmHg). Adequate fluid resuscitation is defined as:

o Intravenous administration of at least 20 mL perkg crystalloid or 10 mL perkg colloid infusion within 6 hours.

OR

o 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 perkg permin (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 is defined as the acute need for mechanical ventilation and PaO2-FiO2 ratio of less than 250 (or less than 200 when lung is the site of infection). For the purposes of this protocol, mechanical ventilation is defined as any type of ventilation administered via an endotracheal tube or nasotracheal intubation. A simple administration of supplemental oxygen is NOT considered to be mechanical ventilation for the purposes of this study.

4. Subjects with coagulopathy characterized by an INR greater than1.40 without other known etiology (e.g., anticoagulant therapy, chronic liver disease)

5. Subjects with coagulopathy characterized by platelet count in the range of greater than 30,000 permm3 to less than 150,000 per mm3 OR a greater than 30 percent decrease in platelets in 24 hours

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 initial or ongoing informed consent (as applicable per local and country regulations)

2.Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of enrolling into the study

3.Subject is of childbearing potential and has a positive pregnancy test since admission to the hospital

4.Subject is less than 18 years of age

5. Subject has a known allergy to ART-123 or any components of the drug product

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

7. Presence of an advance directive to withhold life-sustaining treatment (patients not wishing to receive Cardiopulmonary Resuscitation (CPR) may qualify provided they receive all other resuscitative measures e.g. mechanical ventilation, vasoactive agents, cardioversion).

8.Subject has had previous treatment with ART-123

9.Body weight equal to or greater than 175 kg

10.PT prolongation or thrombocytopenia that is not due to sepsis (e.g. AML or ALL in induction therapy, acute leukemia of the M3 type, myeloablative therapy within 4 weeks prior to enrollment, AIDS with persistent thrombocytopenia and/or bleeding disorder, ongoing pre-existing thrombocytopenia or coagulopathy),Platlets <= 30,000 / mm3 for any reason.

11.Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or non-traumatic orthopedic surgery of the femur or pelvis) within 12 hours prior to the first dose of study drug, or ongoing impairment of hemostasis as a result of one of these procedures.

12.A history of head trauma, spinal trauma, or other acute trauma with an increased risk of bleeding within 3 months prior to consent (subjects with minor head trauma may be enrolled if there is a normal neurological examination and a normal CT scan of the head/spine post injury documented in the medical record).

13.Cerebral Vascular Accident (CVA) within 3 months prior to consent.

14.Any history of Intracerebral Arteriovenous Malformation (AVM), cerebral aneurysm, or mass lesions of the central nervous system.

15.A history of congenital bleeding diatheses (e.g. hemophilia).

16.Significant gastrointestinal bleeding (e.g., melena, hematemesis) within 6 weeks prior to consent unless a corrective interventional procedure has been performed (i.e. endoscopy).

17.Subject is diagnosed with a known medical condition associated with a hypercoagulable state, including:

a.Resistance to activated protein C or known Factor V Leiden

b. Hereditary deficiency of protein C or protein S

c.Presence of anticardiolipin antibody, antiphospholipid antibody, or prothrombin gene mutation

d.Deep-vein thrombosis or pulmonary embolism within 3 months prior to consent (if evaluation is in progress, this should be completed before consideration for this trial)

e.Any disorder with a requirement for full anticoagulation.

18.History of cirrhosis or current Class C liver disease (Child-Pugh score of 10-15)

19. Portosystemic hypertension or known history of bleeding esophageal varices.

20. History of solid organ, allogeneic bone marrow, or stem cell transplantation within the 6 months prior to consent (uncomplicated kidney and autologous stem cell

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
â?¢28 day all-cause mortalityTimepoint: â?¢long term survival status at the 3 month, 6 month and 12 month time points

Secondary Outcome Measures

Name	Time	Method
â?¢Follow-up of all-cause mortality at 3 months <br/ ><br>â?¢Resolution of Organ Dysfunction through Day 28 as measured by <br/ ><br>oShock free and alive days <br/ ><br>oVentilator free and alive days <br/ ><br>oDialysis free and alive daysTimepoint: long term survival status at the 3 month, 6 month and 12 month time points