Exploratory efficacy and safety, pharmacokinetics and dose-finding study of ATryn® (antithrombin alfa) in patients with disseminated intravascular coagulation associated with severe sepsis

• Conditions: Disseminated intravascular coagulation associated with severe sepsis; MedDRA version: 8.1Level: LLTClassification code 10013442Term: Disseminated intravascular coagulation; MedDRA version: 9.1Level: LLTClassification code 10040047Term: Sepsis

• Registration Number: EUCTR2006-002873-35-FR
• Lead Sponsor: EO Pharma A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

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) with at least three of the following clinical findings: body temperature (rectal, ear or core) > 38°C or < 36°C; heart rate > 90 beats/minute; hyperventilation (evidenced by a respiratory rate of > 20 breaths/minute or a PaCO2 of < 32 mmHg) or mechanical ventilation; leucocyte count > 12000 cells/mgl or < 4000 cells/mgl
and b. Minimum two organ failures (respiratory failure, renal dysfunction, hepatic dysfunction, or metabolic acidosis) or refractory shock and c. Clinical signs of infection caused by a bacterial or fungal pathogen
3. Disseminated intravascular coagulation (>= 5 points on overt or non overt DIC score)
4. Predicted mortality between 30 and 60% (43 to 56 points on Simplified Acute Physiology Score II (SAPS II))
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. Maximum time from diagnosis of first organ failure to randomisation: 48 hours. Maximum time from diagnosis of second organ failure or septic shock to randomisation: 24 hours.
10. 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

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 or currently indicated
6. Anticoagulant treatment with pentasaccharide (e.g. fondaparinux) within 7 days prior to randomisation or currently indicated
7. Conditions other than sepsis anticipated to be terminal within 6 months
8. Known bleeding disorder other than DIC
9. Chronic vegetative state
10. Incurable malignancy with documented metastases
11. Haematological neoplasia during cytostatic treatment
12. Bone marrow aplasia
13. Preexisting dialysis-dependent renal failure
14. Known advanced chronic liver disease corresponding to Child-Pugh class B or C (measured prior to ICU admission outside the current sepsis episode) or any history of bleeding from oesophagus varices
15. Overt, ongoing serious haemorrhage
16. Advanced directive to withhold life-supporting treatment (except cardiopulmonary resuscitation)
17. Major burns involving > 20% of the body surface
18. Platelet count < 30000/mgl (unsupported)
19. Acute Myocardial Infarction within 7 days prior to randomisation having led to cardiogenic shock
20. Recent (within 30 days prior to randomisation) or planned (during 6 days post randomisation) heart surgery with cardio-pulmonary bypass
21. Transplantation within 30 days prior to randomisation
22. History of stroke within the last 90 days prior to randomisation
23. Severe cranial or spinal trauma within the last 90 days before randomisation or known cranial or spinal space occupying lesion
24. Recent (within 30 days prior to randomisation) or planned (during 6 days post randomisation) cranial or spinal surgery (except nontraumatic lumbar puncture)
25. Planned major surgery during 6 days post randomisation except tracheostomy
26. Known or suspected hypersensitivity to component(s) of investigational products or known or suspected hypersensitivity to goats or goat products
27. Current participation in any other interventional clinical trial .
28. Patients who have received treatment with any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within the last 30 days prior to randomisation
29. Previously enrolled in this trial

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified