The Cooling And Surviving Septic Shock Study (CASS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Danish Procalcitonin Study Group
Sponsor:
Collaborators:
TRYG Foundation
Lundbeck Foundation
Information provided by (Responsible Party):
Danish Procalcitonin Study Group
ClinicalTrials.gov Identifier:
NCT01455116
First received: October 15, 2011
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Septic Shock
Procedure: Mild Induced Hypothermia
Phase 2
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Danish Procalcitonin Study Group:

Primary Outcome Measures:
  • Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    All cause


Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 560
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01455116

Contacts
Contact: Jens Ulrik S Jensen, MD, PhD +4528938168 juj@cphiv.dk
Contact: Maria E Johansen, MD +4535455757 mej@cphiv.dk

Locations
Denmark
Jens Ulrik S. Jensen Recruiting
Copenhagen, Capital Region, Denmark, DK-2200
Principal Investigator: Morten Bestle, MD, PhD         
Sponsors and Collaborators
Danish Procalcitonin Study Group
TRYG Foundation
Lundbeck Foundation
Investigators
Study Director: Jens Ulrik S Jensen, MD, PhD Copenhagen HIV Programme, University of Copenhagen
  More Information

No publications provided

Responsible Party: Danish Procalcitonin Study Group
ClinicalTrials.gov Identifier: NCT01455116     History of Changes
Other Study ID Numbers: H-A-2008-086
Study First Received: October 15, 2011
Last Updated: September 23, 2013
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by Danish Procalcitonin Study Group:
Sepsis
Multi organ dysfunction syndrome
Mild Induced Hypothermia

Additional relevant MeSH terms:
Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation

ClinicalTrials.gov processed this record on October 19, 2014