Disseminated intravascular coagulation associated with severe sepsis MedDRA version: 9.1 Level: LLT Classification code 10013442 Term: Disseminated intravascular coagulation MedDRA version: 9.1 Level: LLT Classification code 10040047 Term: Sepsis
Conditions
Interventions
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: antithrombin alfa
CAS Number: 84720-88-7
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Sponsors
LEO Pharmaceutical Products Ltd A/S (LEO Pharma A/S)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent has been obtained from the patient or his/her legally acceptable representative 2. Severe sepsis defined as: a. Systemic inflammatory response syndrome (SIRS) related to the current sepsis episode with at least three of the following clinical findings: body temperature (rectal, ear or core) > 38°C or 90 beats/minute; hyperventilation (evidenced by a respiratory rate of > 20 breaths/minute or a PaCO2 of 12000 cells/microlitre or = 5 points on overt or non overt DIC score) 4. Maximum time from diagnosis of first organ failure to randomisation: 48 hours. Maximum time from diagnosis of DIC to randomisation: 24 hours. 5. At least 18 years of age 6. Males or non-pregnant females. Females of child bearing potential should have a negative urine or serum pregnancy test within 24 hours prior to drug administration 7. Any ethnic origin 8. Patient hospitalised at an intensive care unit (ICU) 9. At the time of enrolment there has to be intent by physicians and families to aggressively treat the patient 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
Exclusion criteria
Exclusion criteria: 1. Previous treatment with an antithrombin concentrate or recombinant human activated protein C (rhAPC) within the current sepsis episode 2. Treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) at any dose within the last 6 or 18 hours before randomisation, respectively 3. Anticipated need for treatment with UFH/LMWH, pentasaccharide (e.g. fondaparinux), oral anticoagulants or thrombolytic agents during 6 days post randomisation (e.g. current VTE, atrial fibrillation, ongoing VTE prophylaxis or hypercoagulable state) 4. Intended treatment with rhAPC during 6 days post randomisation 5. Treatment with oral anticoagulants within the last 48 hours before randomisation and INR above 1.5 6. Treatment with: clopidogrel, glycoprotein IIb/IIIa inhibitors or acetylsalicylic acid at doses >325 mg/day within 5 days prior to randomisation 7. Anticoagulant treatment with pentasaccharide (e.g. fondaparinux) within 7 days prior to randomisation 8. Conditions other than sepsis anticipated to be terminal within 6 months 9. Known bleeding disorder other than DIC 10. Chronic vegetative state 11. Incurable malignancy with documented metastases 12. Haematological neoplasia where cytostatic treatment has been administered within two months prior to randomisation 13. Bone marrow aplasia or treatment induced low platelet count (due to immunosuppressive medication) 14. Preexisting dialysis-dependent renal failure 15. Known advanced chronic liver disease corresponding to Child-Pugh class C (measured prior to ICU admission outside the current sepsis episode) or any history of bleeding from oesophageal varices 16. Overt, ongoing serious haemorrhage 17. Advanced directive to withhold life-supporting treatment (except cardiopulmonary resuscitation) 18. Major burns involving > 20% of the body surface 19. Platelet count < 20000/microlitre (patients should not be included if they require a platelet transfusion to bring their platelet level above 20000/microlitre just prior to randomisation) 20. Acute Myocardial Infarction within 7 days prior to randomisation. Please note that troponin levels may be elevated due to sepsis 21. Recent (within 30 days prior to randomisation) or planned (during 6 days post randomisation) heart surgery with cardio-pulmonary bypass 22. Transplantation within 30 days prior to randomisation 23. History of stroke within the last 90 days prior to randomisation 24. Severe cranial or spinal trauma within the last 90 days before randomisation or known cranial or spinal space occupying lesion, intracerebral arteriovenous malformation or cerebral aneurysm 25. Epidural catheter within 12 hours before randomisation or planned epidural catheter during 6 days post randomisation 26. Recent (within 30 days prior to randomisation) or planned (during 6 days post randomisation) cranial or spinal surgery (except nontraumatic lumbar puncture) 27. Any major surgery with increased high risk of bleeding within 12-hours before randomisation or planned major surgery with increased high risk of bleeding during 6 days post randomisation (except tracheostomy) 28. Trauma patients with increased risk of bleeding e.g. significant contusion to lung, liver or spleen, retroperitoneal bleed, pelvic fracture or compartment syndrome within 48 hour before randomisation 29. Known or suspected hypersensitivity to component(s) of investigational products or known or suspected hypersensitivity to goats or goat products 30. Current participation in any ot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to explore the efficacy and safety of ATryn® for the treatment of disseminated intravascular coagulation (DIC) associated with severe sepsis, when administered by continuous intravenous (IV) infusion over five days. ;Secondary Objective: The secondary objectives are to obtain pharmacokinetic data in patients with DIC associated with severe sepsis and to establish an appropriate dose regimen for phase III.;Primary end point(s): Patients alive on day 28, having had an improvement in the DIC score (overt or non-overt) by at least 2 points between baseline and day 6 and having had no worsening of the Sepsis-related Organ Failure Assessment (SOFA) score between baseline and day 6. | — |
Countries
Denmark, France, Germany, Netherlands, Spain, United Kingdom
Outcome results
None listed