An interventional study of External Cooling in Septic Shock, sponsored by Centre Hospitalier Intercommunal Creteil. Recruiting at 33 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Centre Hospitalier Intercommunal Creteil · Not applicable, Interventional, and Treatment
The best strategy for managing fever in patients with septic shock remains unknown. In a pilot study, the investigators showed that fever control at normothermia allowed a better control of shock and evolution of organ failures. In this second trial the investigators will conduct a multicentre, open-label, randomized controlled, superiority trial in which two strategies will be compared:
Sepsis is a common syndrome responsible for multiple organ failure. Septic shock, defined as sepsis with hyperlactatemia and cardiovascular failure requiring vasopressor infusion despite adequate fluid resuscitation has an extremely high mortality rate. Fever is a frequent disease process during sepsis. Fever increases oxygen consumption and can worsen imbalance between oxygen supply and oxygen requirements. Fever increases inflammation but reduces viral and bacterial growth. The beneficial effects of active fever control on inflammation have been mainly shown in a context of lung injury. Pneumonia represents the first cause of septic shock in developed countries.
In a pilot study (SEPSISCOOL I), we showed that fever treatment using external cooling significantly increased the resolution of shock, improved organ functions and decreased d-14 mortality. Although reduced, hospital mortality was not significantly different. This study was underpowered to allow conclusion on mortality. A more pronounced beneficial effect was observed among the most severely ill patients with elevated serum lactate level.
Fever treatment is commonly applied in septic patients but its impact on survival remains undetermined.
The main objective of the study is to compare two strategies of fever management in febrile (body temperature > 38.3°C) septic shock patients requiring invasive mechanical ventilation and sedation. These patients will be randomly allocated in two arms:
A covariate-adaptive randomization will be used to ensure the comparability of the two groups at each stage of the study. We will use an adaptive multistage population-enrichment design with a pre-specified subgroup of patients with ARDS identified at randomization.
An independent Safety and Data Monitoring Committee will review data on serious adverse events. The decision of study stop for potential harmful effect of one strategy will be let at the entire responsibility of the committee.
One interim analysis will be performed by independent observers after enrolment of half of the population. The assumption that fever treatment is more effective in patients with ARDS will be confirmed or not. According to pre-defined rules based on the conditional power calculated in the two subgroups, the trial will be stopped for futility, continued as planned or continued by enrolling only patients with ARDS.
1,078 studies on the registry are indexed under Shock, Septic; 232 are open to participants now.
This study's planned enrollment of 820 is above the median of 79 across 636 interventional studies indexed under Shock, Septic.
Browse Shock, Septic studies →Centre Hospitalier Intercommunal Creteil is the lead sponsor of 131 studies on the registry; 36 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
External cooling during 48 hours to obtain normothermia
Other: External Cooling
Fever respect without any antipyretic therapy
External Cooling
Mortality
All causes mortality
Time frame: Day 60 from randomization
Evolution of SOFA Score
Sequential Organ Failure Assessment (SOFA) score will be calculated at d1, d2, d3 and d7 and compared between the 2 arms. Higer the score higher the severity of organ dysfunctions. Min 0 Max 24
Time frame: Up to Day 7
Number of ventilator free days
Number of free days will be assessed as proposed by YEHYA et al. Patients who died before d28 will be considered as having 0 free day
Time frame: Day 28
Number of renal replacement therapy free days
Number of free days will be assessed as proposed by YEHYA et al.
Time frame: Day 28
Number of vasopressor free days
Number of free days will be assessed as proposed by YEHYA et al. Shock resolution will be defined by vasopressor stop during at least 24h in the absence of care withdrawing
Time frame: Day 28
Mortality
All causes mortality
Time frame: Day 28
Number of patients with shivering
Shivering will be monitored according to a specific scale
Time frame: Day 2
Number of patients with seizure
Seizure will be clinically documented or reveal by EEG
Time frame: Day 3
Number of patients with hypothermia
Number of patients with body temperature lower than 36°C
Time frame: Day 3
Number of patients with at least 1 episode of cardiac arrhythmia
Patient with new episode of supraventricular or ventricular arrhythmia
Time frame: Day 3
Secondary acquired nosocomial infections
Only the first episode will be taken into account
Time frame: Day 28
Number of patients with ARDS development among patients free of ARDS at inclusion
Secondary acquired ARDS according to Berlin definition
Time frame: Up to Day 3
Acute kidney injury in patients free of RRT at inclusion
Maximal stage of AKI according to the KDIGO definition
Time frame: Up to Day7
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Plan to share: Yes — Strictly anonymized data will be available upon justified request from the coordinating investigator and the study sponsor
Supporting information: Study protocol, Informed consent form, Analytic code
Time frame: After publication upon justified request from the coordinating investigator and the study sponsor
Started Oct 2022 (actual). Primary completion is estimated for Dec 2028, 74 months after the start.
Of 164 non-industry interventional studies with no phase under Shock, Septic, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 41. This study's planned 74 months is above that.
Counting every sponsor, half of 172 studies reached it within 25 months; a quarter within 12 and three quarters within 42.
How these figures are worked out, and which studies are left out of them.
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