| | PI: Richard Wunderink, MD Pager 5-9789 Contact the PI or the Pulmonary Research pager (5-9285) for questions and enrollment | Indications: MICU-DIC / Sepsis | IRB Approval # 1444-021 | Inclusion Criteria* | To be included in the study, subjects must have infection or suspected infection and must be treated with antimicrobial medication(s) for this specific infection. Additionally, a modified ISTH DIC* score of ≥2 related to infection/sepsis using the platelet count and/or INR result plus the presence of at least 3 out of 4 sepsis related SIRS criteria. The four SIRS criteria are described as the following: Temperature >38ºC or <36ºC (core temperature for low range temperature) Heart Rate >90 BPM (unless the subject is treated with β-blockers or heart rate is pacemaker dependent. In these cases, only 2 out of 4 criteria are required) Respiratory Rate >20 BPM or PaCO2<32 mmHg or mechanically ventilated subject WBC >12,000 or <4,000 cells/µL or >10% Band forms
If a single INR test or platelet count qualifies the patient, the diagnosis of modified DIC is made the first time such abnormal test is obtained. To use a combination of INR and Platelet count results to meet the modified DIC score of greater than or equal to 2, these two tests must be performed no more than 12 hours apart. The time the latter test is obtained is the time of diagnosis of modified DIC. Once the patient meets criteria of DIC, a maximum of 36 hours is allowed for consent, randomization and administration of study drug. *Amendment 2 guidelines | Exclusion Criteria* | Unable to provide informed consent, or lack of consent from an acceptable surrogate in the event that the subject is incapable of providing consent Women who are pregnant or breastfeeding or intend to get pregnant within 28 days of enrolling into the study Subjects < 18 years of age Allergy to ART-123 or any components of the drug product Subjects unwilling to allow transfusion of blood or blood products Presence of an advance directive to withhold life-sustaining treatment, with the exception of cardiopulmonary resuscitation (CPR) Subjects not in a hospital ward or unit with continuous and closely monitored health care that is provided to critically ill subjects (i.e. an Intensive Care Unit, or monitored bed unit with a high nurse to subject ratio 1:2 or 1:3) or in process of being admitted to one Previous treatment with ART-123 Subjects who have not dosed within 24 hours of meeting eligibility criteria Subjects whose INR and platelet count abnormalities improve such that they no longer meet inclusion criteria Subjects whose body weight is ≥ 175kg
| Medical Conditions Known conditions that could confound the diagnosis of DIC due to sepsis including DIC due to AML or ALL in induction therapy, or acute leukemia of the M3 type Myeloablative therapy within 4 weeks prior to enrollment AIDS Pre-existing thrombocytopenia or coagulopathy Other known or possible etiology for DIC other than sepsis
Known conditions that increase the risk of bleeding: Major surgery or spinal anesthesia within 12 hours prior to randomization, planned or need for major surgery or spinal anesthesia during the infusion period, or evidence of active bleeding postoperatively A history of severe head trauma requiring hospitalization within 3 months before the randomization (subjects with minor head trauma may be enrolled if there is a completely normal CT scan of the head/spine post injury documented in the medical record) Intracranial surgery, or stroke within 3 months before randomization Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system; A history of congenital bleeding diatheses (e.g hemophilia) Gastrointestinal bleeding within 6 weeks before randomization unless corrective surgery has been performed Acute trauma with increased risk of bleeding or spinal or head trauma
Known medical condition associated with a hypercoagulable state, including: Resistance to activated protein C or known Factor V Leiden Hereditary deficiency of protein C, protein S, or antithrombin III Presence of anticardiolipin antibody, antiphospholipid antibody, lupus anticoagulant, prothrombin gene mutation, or homocysteinemia Recently documented (within 3 months before randomization) deep-vein thrombosis or pulmonary embolism (if evaluation is in progress, this should be completed before consideration for this trial) History of idiopathic thrombosis
Known or suspected severe liver disease including: History of solid organ (excluding uncomplicated kidney), bone marrow or stem cell transplantation Acute pancreatitis with no established source of infection Severe renal failure characterized by
Concomitant Medications Intended use of Xigris® (drotrecogin alfa [activated]) by treating physician (see section 3.2.4) All anticoagulants, antiplatelet agents and antithrombotics are excluded except: Heparin locks/flushes Minute doses of thrombolytics for catheter clearance DVT Prophylaxis with either unfractionated heparin doses no higher than 10000 U SQ within a 24 hour period or with LMWH no higher than recommended prophylactic dose range. However, no switching or alternating between unfractionated heparin and LMWH is allowed during the treatment with study drug and up to Day 14
Laboratory Values Prognostic Assessment Subject’s family, physician, or both not in favor of aggressive treatment of subject or presence of an advance directive to withhold life-sustaining treatment (excluding CPR) Subjects who are likely to have limitations put on their life support, given their preexisting, uncorrectable medical condition or who are not expected to survive 90 days due to their underlying medical condition. This would include subjects with, or suspected to have: Poorly controlled neoplasms or subjects currently receiving chemotherapy New York Heart Association class IV subjects Prior cardiac arrest requiring CPR without fully demonstrated neurological recovery, or subject with imminent death 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 restriction, or documented chronic hypoxia, hypercapnia, secondary polycythemia, severe pulmonary hypertension (>40 mm Hg) or respirator dependency End-stage neurological disorders (e.g., amyotrophic lateral sclerosis – Lou Gehrig's disease)
Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted Participation in another investigational study within 30 days before randomization In the investigator’s opinion the subject whould not participate in the trial
| | * This information is provided as a general guildine. Not all Inclusion / Exclusion Criteria are listed. |
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