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 Coagulatio
- Conditions
- Sepsis and disseminated intravascular coagulation.MedDRA version: 9.1 Level: LLT Classification code 10040047 Term: SepsisMedDRA version: 9.1 Level: LLT Classification code 10013442 Term: Disseminated intravascular coagulation
- Registration Number
- EUCTR2007-002035-81-GB
- Lead Sponsor
- Artisan Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 800
Candidates for this study must meet ALL of the
following criteria:
1. Bacterial infection or suspected bacterial infection and being treated with antimicrobial medication(s).
2. DIC score of =2 using a modified ISTH algorithm
3. Subject presents with >2 of the following sepsis related 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 >38ºC or <36ºC (core temperature for low range temperature)
b. WBC >12,000 or <4,000 cells/µL or >10% Band forms
c. Heart Rate >90 BPM (This criterion can not be used if the subject is treated with
ß-blockers or heart rate is pacemaker dependent).
d. Respiratory Rate >20 BPM or PaCO2<32 mmHg or mechanically ventilated subject
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Candidates for the study will be excluded if ANY of the following criteria are present:
1. Subject or Legally Authorized Representative is unable to provide informed consent
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 does not agree to use a medically acceptable form of contraception for the duration of the trial (28 days or 22 days post the last dose of study drug administration). (see protocol for further details)
4. Subject is < 18 years of age
5. 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, with the exception of cardiopulmonary resuscitation (CPR)
8. Previous treatment with ART-123
9. Body weight = 175kg
10. DIC not due to sepsis (see protocol for further details)
11. Intra-thoracic, intra-abdominal, or intra-cranial surgery, within the previous 12 hours to enrollment, 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 enrollment (see protocol for further details)
13. Cerebral Vascular Accident (CVA) within 3 months prior to enrollment
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
16. Gastrointestinal bleeding within 6 weeks prior to enrollment unless a corrective interventional procedure has been performed
17. 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 antithrombin III
c. Presence of anticardiolipin antibody, antiphosopholipid antibody, lupus anticoagulant, prothrombin gene mutation, or homocysteinemia
d. Deep-vein thrombois 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
18. Known or suspected severe liver disease, as defined by a score of 10-15 (class C) using the Child-Pugh Classification (see Appendix G of protocol)
19. Portosystemic hypertension or known history of bleeding esophageal varices
20. 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)
21. 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 an increased risk for developing hemorrhagic pancreatitis over the duration of the study.
22. Severe renal failure characterized
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and activity of ART-123 in reducing mortality in subjects with sepsis and disseminated intravascular coagulation;<br> Secondary Objective: To assess the efficacy of ART-123 in resolution of DIC in this population<br> To establish the predictive value of a DIC score based on platelet count and INR compared with the ISTH DIC score.<br> To evaluate several coagulation parameters in predicting response to ART-123<br> To obtain an accurate estimate of the risk of death in subjects with DIC and sepsis.<br> To assess the safety of ART-123 in subjects with sepsis and DIC.<br> ;Primary end point(s): The primary analysis will test the difference in the 28-day all-cause mortality rates between treatment groups in the ITT population. The rates will be estimated from the product-limit (Kaplan-Meier) with an asymptotic variance determined from Greenwood’s formula. Missing data will be censored
- Secondary Outcome Measures
Name Time Method