The KyberSept trial

ISRCTN	ISRCTN22931023
DOI	https://doi.org/10.1186/ISRCTN22931023
Protocol serial number	N/A
Sponsor	Aventis Behring LLC (USA)
Funder	Aventis Behring LLC (USA)

Submission date: 05/06/2002
Registration date: 05/06/2002
Last edited: 15/11/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Dale Rublee
Scientific

Aventis Behring LLC
1020 First Avenue
PO Box 61501
King of Prussia
PA 19406
United States of America

Phone	+1 610 878 4833
Email	dale.rublee@aventis.com

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	To determine if high-dose antithrombin III (administered within 6 hours of onset) would provide a survival advantage in patients with severe sepsis and septic shock.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Sepsis
Intervention	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 of 6000 IU per day for 4 days, or an equivalent volume of placebo solution (1% of human albumin).
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Antithrombin III
Primary outcome measure(s)	28-day all-cause mortality in the primary efficacy population.
Key secondary outcome measure(s)	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
Completion date	01/01/2000

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	2314
Key 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
Key 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
Date of first enrolment	01/03/1997
Date of final enrolment	01/01/2000

Locations

Countries of recruitment

United Kingdom
Czech Republic
Denmark
Germany
South Africa
United States of America

Study participating centre

Aventis Behring LLC

King of Prussia
PA 19406
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	Results	17/10/2001	Yes	No
Results article	Results	01/08/2006	Yes	No
Other publications	Quality of life evaluation:	01/08/2002	Yes	No