Sepsis Infections and Infestations Sepsis
Conditions
Interventions
Patients were randomly assigned to receive 30 000 IU antithrombin III (Aventis Behring, Marburg, Germany) with a loading dose of 6000 IU (given over 30 minutes), followed by a continuous IV infusion o
Sponsors
Aventis Behring LLC (USA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult hospitalised men and women (greater than or equal to 18 years) 2. Gave informed consent 3. Met the following criteria within a 6-hour period: 3.1. Clinical evidence of sepsis with a suspected source of infection 3.2. Body temperature (rectal or core) higher than 38.5°C or lower than 35.5°C 3.3. Leukocyte count higher than 10 x 10^3/µL or lower than 3.5 x 10^3/µL 4. Three of the following 6 signs had to be met within the same 6-hour period: 4.1. Tachycardia (heart rate greater than 100/min) 4.2. Tachypnoea (greater than 24/min) or mechanical ventilation because of septic indication 4.3. Hypotension with systolic blood pressure lower than 90 mm Hg despite sufficient fluid replacement or the need of vasoactive agents to maintain systolic blood pressure of 90 mm Hg or greater 4.4. Thrombocytopenia with platelet counts of less than 100 x 103/µL 4.5. Elevated lactate levels (above upper limit of normal range) or metabolic acidosis (pH less than 7.3 or base excess -10 mmol/L) not secondary to respiratory alkalosis 4.6. Oliguria with urine output of less than 20 mL per hour despite sufficient fluid replacement
Exclusion criteria
Exclusion criteria: 1. Advanced directive to withhold life-sustaining treatment (except cardiopulmonary resuscitation) 2. Condition other than sepsis anticipated to be fatal within 28 days 3. Pregnancy or breastfeeding 4. History of hypersensitivity to study medication 5. Treatment with other investigational drugs within the last 30 days 6. Treatment with an antithrombin III concentrate within the last 48 hours 7. Treatment with heparin (except subcutaneous low dose or intravenous [IV] line flushing) or coumarin derivatives 8. Non-steroidal anti-inflammatory drug treatment within previous 2 days 9. Known bleeding disorder or ongoing massive surgical bleeding 10. Platelet count of less than 30 x 10^3/µL 11. Immunocompromised status 12. Acute myocardial infarction (within previous 7 days) 13. Third-degree burns (20% of total body area) 14. Incurable malignancy with documented metastases and life-expectancy of less than 3 months 15. Haematologic neoplasia during cytostatic treatment 16. Bone marrow aplasia 17. Preexisting dialysis-dependent renal failure 18. End-stage liver disease 19. Transplantation (postoperative state) 20. History of stroke within the last year 21. Severe cranial or spinal trauma within the last year 22. Planned cranial or spinal surgery (except nontraumatic lumbar puncture) within the next 48 hours
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-day all-cause mortality in the primary efficacy population. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Survival time within 7 days 2. Length of intensive care unit stay within 7 days 3. Occurrence of new organ dysfunction (according to Logistic Organ Dysfunction score) within 7 days 4. Severity of sepsis was assessed via the Simplified Acute Physiology Score version II(SAPS II) 5. Surgical interventions and bleeding events, recorded for 28 days 6. Other serious adverse events, recorded for 14 days 7. Antithrombin III plasma concentrations (functional) at baseline and after 24 hours 8. Activated partial thromboplastin time and prothrombin time values, assessed at baseline and 3 times daily for days 1 through 5 and on day 7 | — |
Countries
Czech Republic, Denmark, Germany, South Africa, United Kingdom, United States of America
Outcome results
None listed