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Control of Fever in Septic Patients (COVERSEP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04227652
Recruitment Status : Completed
First Posted : January 13, 2020
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital Ostrava

Brief Summary:
The benefits of fever treatment in critically ill patients remains unclear. The aim of the prospective, randomized clinical trial was to verify the hypothesis that the administration of ibuprofen in order to decrease the fever in septic patients without limited cardiorespiratory reserve leads to decreasing their prognosis.

Condition or disease Intervention/treatment Phase
Sepsis Severe Sepsis Septic Shock Drug: Ibuprofen administration Not Applicable

Detailed Description:
Fever is a frequently observed part of the organism's response to infection, and it is a well-known fact that it has positive effects, as it inhibits the growth of microorganisms, and potentiates the activity of anti-microbial agents. On the other hand, fever increases the demand of tissues for oxygen and increases the production of carbon dioxide in tissues. Adapting to these metabolic changes requires an efficient cardiorespiratory apparatus. In other words, in patients with a limited cardiorespiratory reserve (typically patients of higher age or patients with a serious disease of the heart or lungs), the beneficial anti-microbial effect of fever may be masked with cardiorespiratory maladaptation to fever-induced metabolic changes. Indeed, one of the randomized clinical trials investigating the effect of "aggressive" antipyretic strategy used in practice (administration of acetaminophen at the temperature > 38.5 degrees Celsius, and addition of physical cooling should the temperature exceed 39.5 degrees Celsius upon the prognosis of critically ill patients showed that the "aggressive" treatment of fever may result in higher mortality when compared with a "permissive" approach, i.e. an approach when the treatment of fever is initiated only after the body temperature has exceeded 40 degrees Celsius. The study differs remarkably from other studies performed among the population of critically ill patients, and also from studies, which did not manifest the effect of fever treatment upon the mortality of patients, with the age of patients. The average age of patients in both arms of the study was only 47 years of age, whereas the average age of patients in other studies was usually around 60 years of age. It is thus possible to presume that, due to the lower age, the patients in this study possessed a sufficient cardiorespiratory reserve for adaptation to metabolic changes induced with fever, which may have enabled a full manifestation of its anti-microbial effect, and may have led to better patient prognosis. The mortality rate in the group of patients with the "permissive" approach to fever treatment was only 2.6 percent, whereas, in the group of patients with the "aggressive" treatment, the mortality rate was 15.9 percent (p=0.06); due to this fact, the study was prematurely terminated by the Ethics Committee. Based on this study, we decided to test the hypothesis that the administration of ibuprofen in order to decrease the fever would lead to a worsening of the patient prognosis. Ibuprofen was selected due to its potent antipyretic effect, and also due to the fact that the favorable effect of its anti-inflammatory effect upon the prognosis of patients with sepsis has not been fully demonstrated.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study subjects were enrolled in two parallel groups.
Masking: None (Open Label)
Masking Description: No masking was used in the study
Primary Purpose: Treatment
Official Title: Control of Fever in Septic Patients
Actual Study Start Date : September 3, 2013
Actual Primary Completion Date : February 28, 2019
Actual Study Completion Date : March 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

Arm Intervention/treatment
Experimental: Aggressive treatment strategy
The antipyretic strategy was initiated immediately upon increase of the temperature above 38.3°C. The antipyretic strategy consisted of administration of ibuprofen (per-orally or into the nasogastric tube, or rectal administration in the form of a suppository) in therapeutical dose, alway supplemented with physical cooling in cases when the temperature exceeded 39.5°C. The body temperature was measured in the urinary bladder.
Drug: Ibuprofen administration
Administration of ibuprofen, according to treatment recommendations - per orally, into the nasogastric tube, or in the form of a suppository

Experimental: Conservative treatment strategy
The antipyretic strategy was initiated only after the body temperature exceeded 39.5°C. The antipyretic strategy consisted of administration of ibuprofen (per-orally or into the nasogastric tube, or rectal administration in the form of a suppository) in therapeutical dose, alway supplemented with physical cooling in cases when the temperature exceeded 39.5°C. The body temperature was measured in the urinary bladder.
Drug: Ibuprofen administration
Administration of ibuprofen, according to treatment recommendations - per orally, into the nasogastric tube, or in the form of a suppository




Primary Outcome Measures :
  1. SOFA score value [ Time Frame: up to 7 days ]
    The SOFA score (Sequential Organ Failure Assessment) was measured on Day 3 and Day 7


Secondary Outcome Measures :
  1. Serum interleukin-6 level [ Time Frame: up to 7 days ]
    The serum interleukin-6 level was measured on Day 3 and Day 7

  2. Serum procalcitonine level [ Time Frame: up to 7 days ]
    The serum procalcitonine level was measured on Day 3 and Day 7

  3. Serum lactate level [ Time Frame: up to 7 days ]
    The serum lactate level was measured on Day 3 and Day 7

  4. Central venous oxygen saturation [ Time Frame: up to 7 days ]
    The central venous oxygen saturation was measured on Day 3 and Day 7

  5. Duration of artificial ventilation [ Time Frame: 1 month ]
    The duration of artificial ventilation in days was observed

  6. Duration of vasopressor support [ Time Frame: 1 month ]
    The duration of vasopressor support in days was observed

  7. Length of ICU stay [ Time Frame: 1 month ]
    The length of ICU stay in days was observed

  8. Length of hospital stay [ Time Frame: 3 months ]
    The length of hospital stay in days was observed



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age >18 years of age
  • body temperature >38.3°C within 2 consecutive hours
  • anti-microbial therapy for a known or suspected infection

Exclusion Criteria:

  • patients admitted after successful cardiopulmonary resuscitation (CPR)
  • acute myocardial infarction
  • brain injury (traumatic and non-traumatic)
  • transfer from another ICU after 72 hours
  • pregnancy
  • antipyretic medication prior to randomization
  • non-obtaining the informed consent
  • moribund condition
  • high risk of hemodynamic or respiratory maladaptation on the metabolic effect of fever

Information from the National Library of Medicine

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): NCT04227652


Locations
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Czechia
University Hospital Ostrava
Ostrava, Moravian-Silesian Region, Czechia, 70852
Sponsors and Collaborators
University Hospital Ostrava
Investigators
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Principal Investigator: Roman Kula, MD,CSc. University Hospital Ostrava

Publications:
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Responsible Party: University Hospital Ostrava
ClinicalTrials.gov Identifier: NCT04227652    
Other Study ID Numbers: FNO-KARIM-13-COVERSEP
RVO-FNOs/2013-2 ( Other Grant/Funding Number: University Hospital Ostrava )
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: January 14, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There exists no plan to make individual participant data available to other researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital Ostrava:
sepsis
severe sepsis
septic shock
fever
ibuprofen
physiological reserves
Additional relevant MeSH terms:
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Sepsis
Toxemia
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock
Ibuprofen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action