The Cooling And Surviving Septic Shock Study (CASS)

Septic Shock Clinical Trial

— CASS  

Official title:

Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01455116
• Other study ID #: H-A-2008-086
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: October 15, 2011
• Last updated: November 21, 2016
• Start date: November 2011
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: Danish Procalcitonin Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 433
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 120 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Procedure:
• Mild Induced Hypothermia
Induction of hypothermia to a target temperature of 32 - 34 degrees Celsius (90 - 93 degrees Fahrenheit

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Skejby	Aarhus	Jutland
Denmark	Bispebjerg Hospital	Copenhagen	Capital Region
Denmark	Jens Ulrik S. Jensen	Copenhagen	Capital Region
Denmark	Gentofte Hospital	Gentofte	Capital Region
Denmark	Herlev Hospital	Herlev	Capital Region
Denmark	Nordsjællands Hospital, Hillerød	Hillerød	Capital Region
Denmark	Horsens Hospital	Horsens	Jutland
Denmark	Køge Hospital	Køge	Region Sealand
Denmark	Roskilde Hospital	Roskilde	Region Sealand
Netherlands	Academic Medical Center	Amsterdam
United States	Cleveland Clinic - Outcomes Research	Cleveland	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Danish Procalcitonin Study Group	Lundbeck Foundation, TRYG Foundation

Countries where clinical trial is conducted

United States,  Denmark,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	All cause	30 days	Yes
Secondary	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	30 days	Yes
Secondary	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	30 days	Yes
Secondary	Circulatory breakdown/Septic Shock	Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4	Measure on day 4	Yes
Secondary	Cerebral dysfunction	Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)	Day 1-4	Yes
Secondary	Hepatic Failure	Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4	Days 1-4	Yes
Secondary	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	Until Day 4/10	Yes
Secondary	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	Days 1-4 + 1-30	Yes
Secondary	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.	30 days	Yes