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Septic ShockPhase 2/3CASSNCT01455116

The Cooling And Surviving Septic Shock Study (CASS)

A Phase 2/3 study testing Mild Induced Hypothermia in people with Septic Shock, run by Danish Procalcitonin Study Group at 11 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 50 to 120 years
Conditions the study is for
Septic Shock
What is being tested?
Mild Induced Hypothermia
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
433 participants
Where
11 sitesin 3 countries
Study dates
Nov 2011to Nov 2016
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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

Trial locations and contacts

11 sites in 3 countries.

11 sites in 3 countries

Denmark9 sites

  • Aarhus University Hospital, Skejby

    Aarhus, Jutland, 8200

  • Bispebjerg Hospital

    Copenhagen, Capital Region, 2400

  • Jens Ulrik S. Jensen

    Copenhagen, Capital Region, DK-2200

  • Gentofte Hospital

    Gentofte Municipality, Capital Region, 2900

  • Herlev Hospital

    Herlev, Capital Region, 2730

  • Nordsjællands Hospital, Hillerød

    Hillerød, Capital Region, 3400

  • Horsens Hospital

    Horsens, Jutland

  • Køge Hospital

    Køge, Region Sealand, 4600

  • Roskilde Hospital

    Roskilde, Region Sealand, 4000

Other trials in Denmark

United States1 site

  • Cleveland Clinic - Outcomes Research

    Cleveland, Ohio, 44195

Other trials in United States

Netherlands1 site

  • Academic Medical Center

    Amsterdam

Other trials in Netherlands

About this study

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

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.

Read the 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
Being tested
Mild Induced Hypothermia
Keywords
Sepsis, Multi organ dysfunction syndrome, Mild Induced Hypothermia
Medical subject headings
Shock, Septic, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mild Induced HypothermiaProcedure or surgery

    Also called Cooling

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

Study groups in NCT01455116
Study groupRoleWhat they receive
Mild induced hypothermiaExperimentalInduced hypothermia to 32-34 degrees Celsius (90 - 93 degrees Fahrenheit)
Receives: Procedure: Mild Induced Hypothermia
Fever RespectNo interventionStandard of care septic shock therapy according to Surviving Sepsis Campaign guidelines

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality

    All cause

    Measured: 30 days

Secondary outcomes (8)

  1. 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

    Measured: 30 days

  2. 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

    Measured: 30 days

  3. Circulatory breakdown/Septic Shock

    Delta MAP days 1-4 Inotropic Score day 1-4 Achieved discontinuation of inotropics on day 4

    Measured: Measure on day 4

  4. Cerebral dysfunction

    Delta RASS 1-4 CAM-ICU: Days with positive CAM-ICU within 72 h after awakening MiniMentalState Examination (MMSE)

    Measured: Day 1-4

  5. Hepatic Failure

    Delta Bilirubin 1-4 Fraction of subjects with Bilirubin level >21 micromoles/L on day 4

    Measured: Days 1-4

  6. 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

    Measured: Until Day 4/10

  7. 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

    Measured: Days 1-4 + 1-30

  8. 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.

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionNov 2016
  4. Study completionNov 2016

Why it stopped: Futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
433 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01455116
Sponsor's protocol ID
H-A-2008-086
Acronym
CASS
Status last verified
Nov 2016
First submitted
15 Oct 2011
Last updated
22 Nov 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided: The Steering Committee will share data after reviewing study propositions - this to assure quality

Publications

  • 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.

    PubMed 29325753

  • 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.

    PubMed 25466837

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Mild Induced Hypothermia in people with Septic Shock, run by Danish Procalcitonin Study Group at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Denmark, United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Futility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality (time frame: 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01455116, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016; AzTrials last refreshed its copy on 27 Oct 2026.

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