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

Primary Purpose

Septic Shock

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Mild Induced Hypothermia
Sponsored by
Danish Procalcitonin Study Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Sepsis, Multi organ dysfunction syndrome, Mild Induced Hypothermia

Eligibility Criteria

50 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland Clinic - Outcomes Research
  • Bispebjerg Hospital
  • Jens Ulrik S. Jensen
  • Gentofte Hospital
  • Herlev Hospital
  • Nordsjællands Hospital, Hillerød
  • Aarhus University Hospital, Skejby
  • Horsens Hospital
  • Køge Hospital
  • Roskilde Hospital
  • Academic Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Mild induced hypothermia

Fever Respect

Arm Description

Induced hypothermia to 32-34 degrees Celsius (90 - 93 degrees Fahrenheit)

Standard of care septic shock therapy according to Surviving Sepsis Campaign guidelines

Outcomes

Primary Outcome Measures

Mortality
All cause

Secondary Outcome Measures

Renal failure
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
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
Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4
Cerebral dysfunction
Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)
Hepatic Failure
Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4
Coagulatory Failure
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
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
Number of days Free of Organ failure until day 30: Need for Mechanical ventilation, need for inotropic, RIFLE criteria positive, positive CAM-ICU days.

Full Information

First Posted
October 15, 2011
Last Updated
November 21, 2016
Sponsor
Danish Procalcitonin Study Group
Collaborators
TRYG Foundation, Lundbeck Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01455116
Brief Title
The Cooling And Surviving Septic Shock Study (CASS)
Acronym
CASS
Official Title
Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Danish Procalcitonin Study Group
Collaborators
TRYG Foundation, Lundbeck Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock
Keywords
Sepsis, Multi organ dysfunction syndrome, Mild Induced Hypothermia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
433 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mild induced hypothermia
Arm Type
Experimental
Arm Description
Induced hypothermia to 32-34 degrees Celsius (90 - 93 degrees Fahrenheit)
Arm Title
Fever Respect
Arm Type
No Intervention
Arm Description
Standard of care septic shock therapy according to Surviving Sepsis Campaign guidelines
Intervention Type
Procedure
Intervention Name(s)
Mild Induced Hypothermia
Other Intervention Name(s)
Cooling
Intervention Description
Induction of hypothermia to a target temperature of 32 - 34 degrees Celsius (90 - 93 degrees Fahrenheit
Primary Outcome Measure Information:
Title
Mortality
Description
All cause
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Renal failure
Description
RIFLE criteria (R+I+F) eGFR decrease (ml/min/1.73 m2) eGFR decrease to <60 ml/min/1,73) + derivatives of the above
Time Frame
30 days
Title
Respiratory
Description
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
Time Frame
30 days
Title
Circulatory breakdown/Septic Shock
Description
Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4
Time Frame
Measure on day 4
Title
Cerebral dysfunction
Description
Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)
Time Frame
Day 1-4
Title
Hepatic Failure
Description
Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4
Time Frame
Days 1-4
Title
Coagulatory Failure
Description
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
Time Frame
Until Day 4/10
Title
Duration of clinical infection
Description
Delta C-reactive protein day 1-4 Achieved decrease in CRP >30 % from day 1-4 PCT decrease (Quantitative) day 1-10
Time Frame
Days 1-4 + 1-30
Title
Number of days Free of Organ failure
Description
Number of days Free of Organ failure until day 30: Need for Mechanical ventilation, need for inotropic, RIFLE criteria positive, positive CAM-ICU days.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged > 50 years of age. Severe sepsis /septic shock = SIRS + suspected infection+hypotension Mean Arterial Blood Pressure (MAP) <70 mmHg, Admitted to the participating intensive care units (ICU) Indication for intubation 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. 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: Patients are pregnant or breast feeding 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 Persons who are detained under the Act on the use of coercion in psychiatry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Ulrik S Jensen, MD, PhD
Organizational Affiliation
CHIP & PERSIMUNE, Rigshospitalet, University of Copenhagen
Official's Role
Study Director
Facility Information:
Facility Name
Cleveland Clinic - Outcomes Research
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Bispebjerg Hospital
City
Copenhagen
State/Province
Capital Region
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Jens Ulrik S. Jensen
City
Copenhagen
State/Province
Capital Region
ZIP/Postal Code
DK-2200
Country
Denmark
Facility Name
Gentofte Hospital
City
Gentofte
State/Province
Capital Region
ZIP/Postal Code
2900
Country
Denmark
Facility Name
Herlev Hospital
City
Herlev
State/Province
Capital Region
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Nordsjællands Hospital, Hillerød
City
Hillerød
State/Province
Capital Region
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Aarhus University Hospital, Skejby
City
Aarhus
State/Province
Jutland
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Horsens Hospital
City
Horsens
State/Province
Jutland
Country
Denmark
Facility Name
Køge Hospital
City
Køge
State/Province
Region Sealand
ZIP/Postal Code
4600
Country
Denmark
Facility Name
Roskilde Hospital
City
Roskilde
State/Province
Region Sealand
ZIP/Postal Code
4000
Country
Denmark
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
The Steering Committee will share data after reviewing study propositions - this to assure quality
Citations:
PubMed Identifier
29325753
Citation
Itenov TS, Johansen ME, Bestle M, Thormar K, Hein L, Gyldensted L, Lindhardt A, Christensen H, Estrup S, Pedersen HP, Harmon M, Soni UK, Perez-Protto S, Wesche N, Skram U, Petersen JA, Mohr T, Waldau T, Poulsen LM, Strange D, Juffermans NP, Sessler DI, Tonnesen E, Moller K, Kristensen DK, Cozzi-Lepri A, Lundgren JD, Jensen JU; Cooling and Surviving Septic Shock (CASS) Trial Collaboration. Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial. Lancet Respir Med. 2018 Mar;6(3):183-192. doi: 10.1016/S2213-2600(18)30004-3. Epub 2018 Jan 8.
Results Reference
derived
PubMed Identifier
25466837
Citation
Johansen ME, Jensen JU, Bestle MH, Ostrowski SR, Thormar K, Christensen H, Pedersen HP, Poulsen L, Mohr T, Kjaer J, Cozzi-Lepri A, Moller K, Tonnesen E, Lundgren JD, Johansson PI. Mild induced hypothermia: effects on sepsis-related coagulopathy--results from a randomized controlled trial. Thromb Res. 2015 Jan;135(1):175-82. doi: 10.1016/j.thromres.2014.10.028. Epub 2014 Nov 5.
Results Reference
derived

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The Cooling And Surviving Septic Shock Study (CASS)

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