blood poisoning diffuse intravascular clotting
Conditions
Interventions
At randomization, subjects who meet all inclusion criteria and no exclusion
criteria will be randomly assigned, in a 1:1 ratio, to receive ART-123 in a
dose of 0.06 mg/kg/day up to a maximum dose of
Sponsors
Asahi Kasei Pharma America Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Subjects must be receiving treatment in an ICU, or in an acute care setting (e.g., ER, RR) 2) Subjects with - clinical objective evidence of bacterial infection and a known site of infection - currently receiving treatment with antibiotics. - white Blood Cell WBC count greater than (>) 12,000/mm3 or less than () 10%. - temperature of 38ºC. - core or axillary temperature of temperature of 38ºC. For hypothermia a core reading is preferred. ;Note 1: If a subject has a 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 # 2b or 2d 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.
Exclusion criteria
Exclusion criteria: - 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) - Body weight >= 175 kg - 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) within 12 hours prior to the first dose of study drug, or ongoing impairment of hemostasis as a result of one of these procedures - A 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 - A history of congenital bleeding diatheses (e.g. hemophilia) - Significant gastrointestinal bleeding (e.g., melena, hematemesis) within 6 weeks prior to consent unless a corrective interventional procedure has been performed (i.e. endoscopy) - 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 - History of cirrhosis or current Class C liver desease (Child-Pugh score of 10-15 - 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. - Subjects with renal dysfunction defined as: a. Chronic renal failure requiring renal replacement therapy (RRT), or b. Subjects with sepsis induced renal dysfunction (average urine output < 0.3 ml/kg/hr) for greater than 36 hours prior to first qualifying INR whether receiving RRT or not. - Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to consent with the exception of: a. Heparin locks/flushes b. DVT Prophylaxis per prophylactic dosing on the package insert as approved in your country. c. Up to 325mg of aspirin daily for cardiac prophylaxis only d. Anticoagulants for RRT: Regional citrate is preferred. It is recommended that if unfractionated heparin or LMWH is used, that the systemic exposure be less than or equal to the DVT prophylaxis dose allowed. - Life expectancy < 90 days due to underlying conditions such as, but not limited to, the following: a. Poorly controlled neoplasms b. New York Heart Association class IV subjects or pulmonary vascular disease resulting in severe exercise restriction (i.e., unable to climb stairs or perform household duties), or chronic restrictive or obstructive pulmonary disease that also results in severe exercise r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Twenty-eight (28) day all-cause mortality is the generally accepted primary efficacy outcome for sepsis treatments. Because ART-123 acts on the coagulation pathway, major bleeding events will be considered as a safety endpoint, together with adverse events and other serious adverse events. Primary Efficacy Endpoint: • 28 day all-cause mortality | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoints: • Follow-up of all-cause mortality at 3 months • Resolution of Organ Dysfunction through Day 28 as measured by o Shock free and alive days o Ventilator free and alive days o Dialysis free and alive days Tertiary Efficacy Endpoints: • Follow-up of all-cause mortality at 6 and 12 months • Organ Dysfunction (Hepatic, Renal, Respiratory and Cardiac (Septic Shock) at Baseline, Day 3, Day 7, Day 14 and Day 28 • ICU free and alive days through Day 28 • Hospitalization free and alive days through Day 28 • INR at Baseline, Day 3, Day 7, Day 14 and Day 28 Safety Primary Safety Endpoints: • Serious Adverse Events • Major Bleeding Events • Adverse Events Secondary Safety Endpoint: • Anti-drug antibodies | — |
Countries
Netherlands
Outcome results
None listed