Fever Control Using External Cooling in Mechanically Ventilated Patients With Septic Shock
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|ClinicalTrials.gov Identifier: NCT04494074|
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : November 3, 2022
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:
- Respect of fever
- Fever control at normothermia using external cooling The primary end point will be d-60 mortality.
|Condition or disease||Intervention/treatment||Phase|
|Septic Shock||Other: External Cooling||Not Applicable|
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:
- Fever respect
- Fever control by external cooling to obtain normothermia during 48 hours
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||820 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Intérêt du Traitement de la fièvre Par Refroidissement Externe Pour la Survie Des Patients ventilés en Choc Septique|
|Actual Study Start Date :||October 1, 2022|
|Estimated Primary Completion Date :||December 1, 2022|
|Estimated Study Completion Date :||December 1, 2024|
Experimental: Fever Control by external cooling
External cooling during 48 hours to obtain normothermia
Other: External Cooling
No Intervention: Fever respected, no cooling
Fever respect without any antipyretic therapy
- Mortality [ Time Frame: Day 60 ]All causes mortality
- Evolution of SOFA Score [ Time Frame: Up to Day 7 ]
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
- Number of ventilator free days [ Time Frame: Day 28 ]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
- Number of renal replacement therapy free days [ Time Frame: Day 28 ]Number of free days will be assessed as proposed by YEHYA et al.
- Number of vasopressor free days [ Time Frame: Day 28 ]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
- Mortality [ Time Frame: Day 28 ]All causes mortality
- Number of patients with shivering [ Time Frame: Day 2 ]Shivering will be monitored according to a specific scale
- Number of patients with seizure [ Time Frame: Day 3 ]Seizure will be clinically documented or reveal by EEG
- Number of patients with hypothermia [ Time Frame: Day 2 ]Number of patients with body temperature lower than 36°C
- Number of patients with at least 1 episode of cardiac arrhythmia [ Time Frame: Day 3 ]Patient with new episode of supraventricular or ventricular arrhythmia
- Secondary acquired nosocomial infections [ Time Frame: Day 28 ]Only the first episode will be taken into account
- Number of patients with ARDS development among patients free of ARDS at inclusion [ Time Frame: Up to Day 3 ]Secondary acquired ARDS according to Berlin definition
- Acute kidney injury [ Time Frame: Up to Day7 ]Maximal stage of AKI according to the KDIGO definition
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04494074
|Contact: Frédérique SCHORTGEN, MD||01 45 17 56 83||Frederique.firstname.lastname@example.org|
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