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The Cooling And Surviving Septic Shock Study (CASS) (CASS)

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ClinicalTrials.gov Identifier: NCT01455116
Recruitment Status : Terminated (Futility)
First Posted : October 19, 2011
Last Update Posted : November 22, 2016
TRYG Foundation
Lundbeck Foundation
Information provided by (Responsible Party):
Danish Procalcitonin Study Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Septic Shock Procedure: Mild Induced Hypothermia Phase 2 Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 433 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock
Study Start Date : November 2011
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia Shock

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Mortality [ Time Frame: 30 days ]
    All cause

Secondary Outcome Measures :
  1. Renal failure [ Time Frame: 30 days ]

    RIFLE criteria (R+I+F) eGFR decrease (ml/min/1.73 m2) eGFR decrease to <60 ml/min/1,73)

    + derivatives of the above

  2. Respiratory [ Time Frame: 30 days ]

    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

  3. Circulatory breakdown/Septic Shock [ Time Frame: Measure on day 4 ]
    Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4

  4. Cerebral dysfunction [ Time Frame: Day 1-4 ]
    Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)

  5. Hepatic Failure [ Time Frame: Days 1-4 ]
    Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4

  6. Coagulatory Failure [ Time Frame: Until Day 4/10 ]
    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

  7. Duration of clinical infection [ Time Frame: Days 1-4 + 1-30 ]
    Delta C-reactive protein day 1-4 Achieved decrease in CRP >30 % from day 1-4 PCT decrease (Quantitative) day 1-10

  8. Number of days Free of Organ failure [ Time Frame: 30 days ]

    Number of days Free of Organ failure until day 30:

    Need for Mechanical ventilation, need for inotropic, RIFLE criteria positive, positive CAM-ICU days.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Aged > 50 years of age.
  2. Severe sepsis /septic shock = SIRS + suspected infection+hypotension Mean Arterial Blood Pressure (MAP) <70 mmHg,
  3. Admitted to the participating intensive care units (ICU)
  4. Indication for intubation
  5. Possibility of inclusion within 6 hours after septic shock/severe sepsis is diagnosed in the ICU. Patients admitted with septic shock/severe sepsis should be included within 6 hours after admission. If a patient is not included within this period, that patient cannot be included within the same hospitalization.
  6. The patient must have an expected stay in the ICU of more than 24 hours. Anticipated death within 24 hours after admission to the ICU does not exclude participation; however no decision of reduction of treatment level must have been taken. During this time period, probability that the patient is discharged to a floor department must not be likely (<10% probability).

Exclusion Criteria:

  1. Patients are pregnant or breast feeding
  2. The findings of the initial screening, shows that the patient has a bleeding disorder and/or the patient has an uncontrollable bleeding and /or surgery within the last 24 hours
  3. Persons who are detained under the Act on the use of coercion in psychiatry

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01455116

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United States, Ohio
Cleveland Clinic - Outcomes Research
Cleveland, Ohio, United States, 44195
Bispebjerg Hospital
Copenhagen, Capital Region, Denmark, 2400
Jens Ulrik S. Jensen
Copenhagen, Capital Region, Denmark, DK-2200
Gentofte Hospital
Gentofte, Capital Region, Denmark, 2900
Herlev Hospital
Herlev, Capital Region, Denmark, 2730
Nordsjællands Hospital, Hillerød
Hillerød, Capital Region, Denmark, 3400
Aarhus University Hospital, Skejby
Aarhus, Jutland, Denmark, 8200
Horsens Hospital
Horsens, Jutland, Denmark
Køge Hospital
Køge, Region Sealand, Denmark, 4600
Roskilde Hospital
Roskilde, Region Sealand, Denmark, 4000
Academic Medical Center
Amsterdam, Netherlands
Sponsors and Collaborators
Danish Procalcitonin Study Group
TRYG Foundation
Lundbeck Foundation
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Study Director: Jens Ulrik S Jensen, MD, PhD CHIP & PERSIMUNE, Rigshospitalet, University of Copenhagen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Danish Procalcitonin Study Group
ClinicalTrials.gov Identifier: NCT01455116    
Other Study ID Numbers: H-A-2008-086
First Posted: October 19, 2011    Key Record Dates
Last Update Posted: November 22, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The Steering Committee will share data after reviewing study propositions - this to assure quality
Keywords provided by Danish Procalcitonin Study Group:
Multi organ dysfunction syndrome
Mild Induced Hypothermia
Additional relevant MeSH terms:
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Shock, Septic
Pathologic Processes
Systemic Inflammatory Response Syndrome