The Cooling And Surviving Septic Shock Study (CASS)

NCT ID: NCT01455116

Last Updated: 2016-11-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 433 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2016-11-30

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.

Conditions

Septic Shock

Keywords

Sepsis; Multi organ dysfunction syndrome; Mild Induced Hypothermia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mild induced hypothermia

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

Group Type: EXPERIMENTAL

Mild Induced Hypothermia

Intervention Type: PROCEDURE

Induction of hypothermia to a target temperature of 32 - 34 degrees Celsius (90 - 93 degrees Fahrenheit

Fever Respect

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Mild Induced Hypothermia

Induction of hypothermia to a target temperature of 32 - 34 degrees Celsius (90 - 93 degrees Fahrenheit

Intervention Type: PROCEDURE

Other Intervention Names

Cooling

Eligibility 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TRYG Foundation

OTHER

Sponsor Role: collaborator

Lundbeck Foundation

OTHER

Sponsor Role: collaborator

Danish Procalcitonin Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jens Ulrik S Jensen, MD, PhD

Role: STUDY_DIRECTOR

CHIP & PERSIMUNE, Rigshospitalet, University of Copenhagen

Locations

Cleveland Clinic - Outcomes Research

Cleveland, Ohio, United States

Bispebjerg Hospital

Copenhagen, Capital Region, Denmark

Jens Ulrik S. Jensen

Copenhagen, Capital Region, Denmark

Gentofte Hospital

Gentofte Municipality, Capital Region, Denmark

Herlev Hospital

Herlev, Capital Region, Denmark

Nordsjællands Hospital, Hillerød

Hillerød, Capital Region, Denmark

Aarhus University Hospital, Skejby

Aarhus, Jutland, Denmark

Horsens Hospital

Horsens, Jutland, Denmark

Køge Hospital

Køge, Region Sealand, Denmark

Roskilde Hospital

Roskilde, Region Sealand, Denmark

Academic Medical Center

Amsterdam, , Netherlands

Countries

United States; Denmark; Netherlands

References

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.

Reference Type: DERIVED

PMID: 29325753 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25466837 (View on PubMed)

Other Identifiers

H-A-2008-086

Identifier Type: -

Identifier Source: org_study_id