- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04227652
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
Conditions
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
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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.
Sponsor
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.
General Publications
- Schulman CI, Namias N, Doherty J, Manning RJ, Li P, Elhaddad A, Lasko D, Amortegui J, Dy CJ, Dlugasch L, Baracco G, Cohn SM. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt). 2005 Winter;6(4):369-75. doi: 10.1089/sur.2005.6.369. Erratum In: Surg Infect (Larchmt). 2010 Oct;11(5):495. Li, Pam [corrected to Li, Pamela]; Alhaddad, Ahmed [corrected to Elhaddad, Ahmed].
- Young P, Saxena M, Bellomo R, Freebairn R, Hammond N, van Haren F, Holliday M, Henderson S, Mackle D, McArthur C, McGuinness S, Myburgh J, Weatherall M, Webb S, Beasley R; HEAT Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med. 2015 Dec 3;373(23):2215-24. doi: 10.1056/NEJMoa1508375. Epub 2015 Oct 5.
- Ye S, Xu D, Zhang C, Li M, Zhang Y. Effect of Antipyretic Therapy on Mortality in Critically Ill Patients with Sepsis Receiving Mechanical Ventilation Treatment. Can Respir J. 2017;2017:3087505. doi: 10.1155/2017/3087505. Epub 2017 Mar 12.
- Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med. 1997 Mar 27;336(13):912-8. doi: 10.1056/NEJM199703273361303.
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
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Systemic Inflammatory Response Syndrome
- Inflammation
- Shock
- Sepsis
- Toxemia
- Shock, Septic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Ibuprofen
Other Study ID Numbers
- FNO-KARIM-13-COVERSEP
- RVO-FNOs/2013-2 (Other Grant/Funding Number: University Hospital Ostrava)
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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