In This SectionTexas Health Research & Education Institute
Disease or Condition
A Randomized, Double-Blind, Placebo-Controlled, Phase-2B Study to Assess the Safety and Efficacy Effects of ART-123 on Subjects with Sepsis and Disseminated Intravascular Coagulation (Critical Care)
This is a study using ART-123, or a placebo, in subjects with Disseminated Intravascular Coagulation (DIC) due to sepsis. DIC is an activation of blood clotting mechanisms that happens in response to a variety of diseases. As its name suggests, it leads to the formation of small blood clots inside the blood vessels throughout the body. As the small clots consume all the available proteins and platelets, normal clotting is disrupted and abnormal bleeding occurs from the sken, the digestive tract, the respiratory tract and surgical wounds. The small clots also disrupt normal blood flow to organs (such as the kidneys) which may cause them to malfunction also. DIC is common in the critically ill, and may lead to multiple organ failure, which may lead to death.
Bacterial or suspected bacterail infection and being treated with antimicrobial medication(s).
DIC score >_2 using a modified ISTH algorithm.
Subject presents with >_2 of the following sepsis realted SIRS criteria within the 24 hours prior to any particular qualifying DIC score, with one of the two criteria being either temperature or WBC:
a. Temperature >38C or <36C (core temperature for lwo range temperature)
b. WBC >12,000 or <4,000 cells/uL or >10% Band forms
c. Heart Rate >90 BPM (This criterion cannot be used if the subject is treated with b-blockers or heart rate is pacemaker dependent)
d. Respiratory Rate >20 BPM or PaCO2 <32mmHg or mechanically ventilated subject.
Subject or Legally Authorized Representative is unable to provide informed consent.
Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of enrolling in the study.
Subject is of childbearing potential and does not agree to use a medically acceptable form of contraception f
or the duration of trial (28 days after the last dose of study drug administration). Medically acceptable forms of contraception include:
a. Contraceptive Medication
b. Intrauterine Device
c. Double Barrier Methods
d. Tubal ligation.
Subject is <18 years of age.
Allergy to ART-123 or any components of the drug product.
Subject is 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).
Previous treatment with ART-123.
Body weight >_ 175kg.
DIC 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 enrolment, AIDS with persistent thrombocytopenia and/or bleeding disorder, pre-existing thrombocytopenia, or coagulapathy that would confound the diagnosis of DIC).
Intra-thoracic, intra-abdominal, or intra-cranial surgery, within the previous 12 hours to enrollment, or ongong 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 enrollment (subjects with monor heard 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).
Cerebral Vascular Accident (CVA) within 3 months prior to enrollment.
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).
Gastrointestinal bleeding within 6 weeks prior to enrollment unless a corrective intervention procedure has been performed.
Known medical conditions associated with a hypercoagulable state, including:
a. Resistance to activated protein C or known Factor V Leiden
b. Hereditary deficiency of Protein C, protein S, or antithrobmbin III
c. Presence of anticardiolipin antibody, antiphospholipid antibody, lupus antcoagulant, prothrombin gene mutation, or homycysteinemia
d. Deep-vein thrombosis or pulmonary embolism within 3 months prior to enrollment (if evaluation is in progress, this should be completed before consideration for this trial)
e. History of idiopathic thrombosis.
Known or suspected severe liver disease, as defined by a score of 10-15 (Class C) using the Child-Pugh Classification.
Portosytemic hypertension or known history of bleeding esophagela varices.
History of solid organ, allogeneic bone marrow, or stem cell transplantation within 6 months of enrollment (uncomplicated kidney and autologous stem cell/bone marrow transplant subjects may be enrolled at any time after they have recovered from their transplant procedure).
Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture. Also, in the opinion of the treating physician the subject is at an increased risk for developing hemorrhagic pancreatits over the duration of the study.
Severe renal failure charactized by chronic or acute need of hemodialysis, hemofiltration or peritoneal dialysis.
Use or intended use of Xigris (drotrecogin alfa [activated]) within 24 hours prior of enrollment.
Use of intended use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 24 hours prior to study dosing with the exception of:
a. Heparin locks/flushes
b. DVT Prophylaxis with either unfrationated heparin at total daily doses no higher than 10,000 U SQ or LMWH at a total daily dose no higher than 15000 U SQ (no switching or alternating between unfractionated heparin and LMWH is allowed during treatment and up to Study Day 14
c. Up to 325mg of aspirin daily for cardiac prophylaxis.
Platelet count <20,000 OR platelet count <30,000 after platelet transusion.
Life expectancy <90 days due, but not limited to, the following conditions:
a. Poorly controlled neoplasms
b. New York Heart Association Class IV subjects or pulmonary vascular disease resultingin 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 (mean arterial pulmonary pressure >40mm Hg) or respirator dependency
c. Prior cardiac arrest requiring CPR without fully demonstrated neurological recover, or subject with imminent death.
d. End-stage neurological disorders (e.g., amyotrophic lateral sclerosis - Lou Gehrig's disease).
Use of any chemotherapy agent.
Participation in another research study involving an investigational agent witin 30 days prior to enrollment.