Control of Fever in Septic Patients (COVERSEP)

January 11, 2020 updated by: University Hospital Ostrava
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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Moravian-Silesian Region
      • Ostrava, Moravian-Silesian Region, Czechia, 70852
        • University Hospital Ostrava

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
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.
Administration of ibuprofen, according to treatment recommendations - per orally, into the nasogastric tube, or in the form of a suppository

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SOFA score value
Time Frame: up to 7 days
The SOFA score (Sequential Organ Failure Assessment) was measured on Day 3 and Day 7
up to 7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum interleukin-6 level
Time Frame: up to 7 days
The serum interleukin-6 level was measured on Day 3 and Day 7
up to 7 days
Serum procalcitonine level
Time Frame: up to 7 days
The serum procalcitonine level was measured on Day 3 and Day 7
up to 7 days
Serum lactate level
Time Frame: up to 7 days
The serum lactate level was measured on Day 3 and Day 7
up to 7 days
Central venous oxygen saturation
Time Frame: up to 7 days
The central venous oxygen saturation was measured on Day 3 and Day 7
up to 7 days
Duration of artificial ventilation
Time Frame: 1 month
The duration of artificial ventilation in days was observed
1 month
Duration of vasopressor support
Time Frame: 1 month
The duration of vasopressor support in days was observed
1 month
Length of ICU stay
Time Frame: 1 month
The length of ICU stay in days was observed
1 month
Length of hospital stay
Time Frame: 3 months
The length of hospital stay in days was observed
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Roman Kula, MD,CSc., University Hospital Ostrava

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2013

Primary Completion (Actual)

February 28, 2019

Study Completion (Actual)

March 31, 2019

Study Registration Dates

First Submitted

January 10, 2020

First Submitted That Met QC Criteria

January 10, 2020

First Posted (Actual)

January 13, 2020

Study Record Updates

Last Update Posted (Actual)

January 14, 2020

Last Update Submitted That Met QC Criteria

January 11, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There exists no plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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