The Cooling And Surviving Septic Shock Study (CASS)
Septic shock is in critically ill patients is a condition associated with a high rate of organ failure and hereto attributable mortality ~45-55% Hypothesis: Mild Induced Hypothermia reduces the mortality of critically ill patients with septic shock by reducing organ metabolism, counteracting on microcirculatory thrombosis, genetically downregulating tissue apoptosis and by reducing bacterial growth rate and toxin production.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock|
- Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]All cause
- Renal failure [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
RIFLE criteria (R+I+F) eGFR decrease (ml/min/1.73 m2) eGFR decrease to <60 ml/min/1,73)
+ derivatives of the above
- Respiratory [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
Use of Mechanical Ventilation on day 4 No. of days where Mechanical Ventilation is used Delta PaO2/FiO2 ratio until day 4
+Derivatives of the above
- Circulatory breakdown/Septic Shock [ Time Frame: Measure on day 4 ] [ Designated as safety issue: Yes ]Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4
- Cerebral dysfunction [ Time Frame: Day 1-4 ] [ Designated as safety issue: Yes ]Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)
- Hepatic Failure [ Time Frame: Days 1-4 ] [ Designated as safety issue: Yes ]Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4
- Coagulatory Failure [ Time Frame: Until Day 4/10 ] [ Designated as safety issue: Yes ]Delta Platelets day 1-4 Delta INR days 1-4 (and factor 2/7/10) Delta APTT (days 1-4) Total consumption of SAG-M on days 1-10 Occurrence of Severe bleeding (surgery demanding or CT-verified, fresh upper or lower G-I bleeding) Thromboelastography
- Duration of clinical infection [ Time Frame: Days 1-4 + 1-30 ] [ Designated as safety issue: Yes ]Delta C-reactive protein day 1-4 Achieved decrease in CRP >30 % from day 1-4 PCT decrease (Quantitative) day 1-10
- Number of days Free of Organ failure [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
Number of days Free of Organ failure until day 30:
Need for Mechanical ventilation, need for inotropic, RIFLE criteria positive, positive CAM-ICU days.
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Mild induced hypothermia
Induced hypothermia to 32-34 degrees Celsius (90 - 93 degrees Fahrenheit)
Procedure: Mild Induced Hypothermia
Induction of hypothermia to a target temperature of 32 - 34 degrees Celsius (90 - 93 degrees Fahrenheit
Other Name: Cooling
No Intervention: Fever Respect
Standard of care septic shock therapy according to Surviving Sepsis Campaign guidelines
Septic shock is an acute life-threatening condition, with great organ damage for every hour. The patients have a high risk of dying and therefore rapid treatment is of crucial importance for survival of the patients.
Septic shock is mainly due to a collapse in the blood circulation (the capillary system) due to blockage by blood cells - a process initiated by substances from the cells of the immune system via activation of coagulation. The normal function of the smallest blood vessels is to transport oxygen, nutrients and drugs to organs and tissues, and lead waste products away. While the offer of oxygen and nutrients to the organs decreases, the consumption of oxygen and nutrients increases due to fever and immune reactions.
When the capillary system collapses, the organs and tissues suffer, and various forms of cell death in the organs begins including "programmed cell death" ("apoptosis"). This leads to organ damage, for example brain damage or kidney damage and ultimately to multiple organ dysfunction which is the direct cause of the patient dies.
Mild induced hypothermia (cooling to 32 0C-34 0C) affects at least 5 core areas in the pathophysiology of septic shock: 1) inhibition of inflammation 2) inhibition of apoptosis ("programmed cell death"), 3) antithrombotic, 4) decreases the metabolism and 5) inhibits bacterial growth and production of toxins.
|Contact: Jens Ulrik S Jensen, MD, PhDemail@example.com|
|Contact: Maria E Johansen, MDfirstname.lastname@example.org|
|Jens Ulrik S. Jensen||Recruiting|
|Copenhagen, Capital Region, Denmark, DK-2200|
|Principal Investigator: Morten Bestle, MD, PhD|
|Study Director:||Jens Ulrik S Jensen, MD, PhD||Copenhagen HIV Programme, University of Copenhagen|