Immunomodulatory Properties of Ketamine in Sepsis

Sepsis Clinical Trial

Official title:

Immunomodulatory Properties of Ketamine in Sepsis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01089361
• Other study ID #: 2009-P-000259
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: March 12, 2010
• Last updated: October 19, 2010
• Start date: December 2009
• Est. completion date: June 2011

Study information

• Verified date: October 2010
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to assess the effect of short-term infusion of ketamine at analgesic dosage on the immune response, morbidity and mortality among patients suffering from septic shock. We hypothesize that ketamine will modulate the cytokine response to sepsis and reduce morbidity and mortality.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: June 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Patients meeting the ACCP/ SCCM definition of severe sepsis will be enrolled in the study. These patients should have a known or suspected source of infection.

• Patients within 12 hours of the development of one or more organ dysfunctions

• Patients must exhibit 3 or more of the following signs of clinical inflammation:

• Core temperature < 36ºC or > 38ºC.

• Heart rate of 90 or greater not explained by another medical condition.

• A respiratory rate of > 20 min-1, a PaCO2 < 32min-1 or the need for mechanical ventilation.

• A white blood cell count of < 4000 cell/ml or > 12000 cells/ml or a WBC showing greater then 10% immature neutrophils.

Exclusion Criteria:

• pregnant

• increased intracranial pressure or closed head injury

• history of psychotic mental disease

• receiving Continuous Veno - Venous Hemofiltration

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Ketamine
The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.
• Normal Saline placebo
The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

Calandra T, Bochud PY, Heumann D. Cytokines in septic shock. Curr Clin Top Infect Dis. 2002;22:1-23. Review. — View Citation

Kawasaki T, Ogata M, Kawasaki C, Ogata J, Inoue Y, Shigematsu A. Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesth Analg. 1999 Sep;89(3):665-9. — View Citation

Laudanski K, Miller-Graziano C, Xiao W, Mindrinos MN, Richards DR, De A, Moldawer LL, Maier RV, Bankey P, Baker HV, Brownstein BH, Cobb JP, Calvano SE, Davis RW, Tompkins RG. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15564-9. Epub 2006 Oct 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum levels of IL-6, IL-10 and TNFa and other cytokines		first 7 days of admission	No
Secondary	Adverse effects attributable to ketamine		7 days	Yes
Secondary	Organ failures	Incidence of new organ failure as detected by Sequential Organ Failure Assessment [SOFA] score. Definitions are as follows. Central nervous system: delirium, coma, uncontrollable seizures, ICP>20cm H2O Cardiac: MAP <60mmHg, blood pressure supported with pressors, 50 > HR > 120 Respiratory: vented, RR>30, PaO2<60, PaCO2 > 55, Sat<92% Kidney: RIFLE criteria Anemia: Hct<27, transfusion of PRBC Thrmobocytopenia: platelet < 50k, platelet transfusion Liver: biopsy, ALT>200, AST>200, t.bil>2.0, ALP>300 Coaugulation failure: INR>2 if no anticoagulation therapy	7 days	Yes
Secondary	Daily Acute Physiology and Chronic Health Evaluation (APACHE) scores	Difference in average APACHE-II score between the intervention and placebo groups. The point score is calculated from 12 routine physiological measurements (such as blood pressure, body temperature, heart rate etc.) during the first 24 hours after admission, information about previous health status and some information obtained at admission (such as age).	7 days	No
Secondary	Length of intensive care unit (ICU) stay		28 days	No
Secondary	28 day mortality		28 days	No