- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01173367
Anti-pyretic Therapy in Critically Ill Adults
Assessment of the Safety of Anti-pyretic Therapy in Critically Ill Adults
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The impact of fever and its management in different medical and surgical populations of critically ill patients has not been explained to date. Clinical trials in critically ill surgical patients have demonstrated null or potentially harmful effects of treatment of moderate degrees of fever. However, the pathophysiological effects of fever treatment are not well defined according to different patient populations, and clinical trial results are questionably generalized to medical ICU patients. This may relate to different mechanisms of fever in these populations and merits further investigation. There is also very little known about the exact timing of expression of the diverse pro and anti-inflammatory mediators involved in inducing, maintaining and eventually abrogating the fever response. Treating on the sole basis of an elevated temperature may lead to detrimental effects if the anti-inflammatory cascade naturally regulating this response is active, demonstrating the importance of understanding the normal pattern of regulation of these diverse mediators. The current study aims to assess the safety and efficacy of treatment of critically ill patients with a permissive versus aggressive fever treatment strategy. In addition, the effect of anti-pyretic therapy on markers of inflammation in neurologically intact critically ill adults will be evaluated.
The study population will be neurologically intact febrile adults (≥18 years) admitted to the Peter Lougheed Center (PLC) or Foothills Medical Center (FMC) ICU over a 12-month period in Calgary, Alberta, Canada. Consenting patients that fulfill enrolment criteria will be randomly allocated to either the permissive or aggressive treatment group (see Interventions section for details). Randomization will be concealed using the consecutively numbered sealed opaque envelope technique. Samples of blood will be collected from study patients at enrolment and subsequently at 12, 24 and 48 hours for assessment of inflammatory mediators.
Markers of feasibility will include the rate of enrolment, adherence of patients to assigned treatment regimen/protocol violation, acceptance of the protocol by staff, and facility and maintenance of random allocation technique. Markers of safety will include potential adverse events such as 28-day survival, nosocomial infection rate, and evidence of myocardial ischemia, or hepatocellular inflammation during the febrile episode.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alberta
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Calgary, Alberta, Canada, T1Y 6J4
- Intensive Care Unit, Peter Lougheed Center
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Calgary, Alberta, Canada, T2N 2T9
- Intensive Care Unit, Foothills Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years old
- Fever (two consecutive measurements ≥ 38.3°C at least 2 hours apart or a single temperature measurement ≥ 39.5°C)
- Admitted to ICU with an expected length of stay at least 48 hours related to critical illness
- Attending physician approval
Exclusion Criteria:
- Admission to ICU for support for specific procedure (e.g. endoscopy, acute dialysis, bronchoscopy)
- Acute brain injury due to any etiology
- Acute myocardial ischemia
- Documented hepatitis with elevated alanine aminotransferase (ALT) more than twice the upper limit of normal, or chronic hepatic failure (defined by evidence of cirrhosis on available imaging or known varices, ascites, hepatic encephalopathy, hepatorenal syndrome, and/or hepatocellular carcinoma)
- Hyperthermia syndromes (malignant hyperthermia, heat stroke, neuroleptic malignant syndrome, serotonin syndrome, or endocrine causes including thyrotoxicosis, pheochromocytoma, and adrenal crisis)
- Refractory shock with lactic acidosis >4 mmol/L (at the time of screening for study enrollment) despite supportive therapy or need for paralytic treatment to reduce metabolic demand
- Requirement for use of anti-pyretic agents (acetaminophen or NSAIDs) for indications other than treatment of fever
- Receipt of anti-pyretic pharmacotherapy within 6-hours of expected study enrollment (650mg acetaminophen, 800mg ibuprofen, or 325mg acetylsalicylic acid)
- Contraindications to esophageal temperature monitoring
- Pregnancy (all women of child-bearing potential need to have a pregnancy test performed prior to enrollment)
- Time from onset of fever in the ICU to consideration for study enrollment is > 12 hours
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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ACTIVE_COMPARATOR: Aggressive Fever Treatment
|
Patients assigned to the aggressive fever treatment protocol will receive acetaminophen 650 mg enterally every 6 hours for fever ≥ 38.3°C and external cooling will be initiated for temperatures ≥ 39.5°C.
Acetaminophen and external cooling will be discontinued once core temperature is less than 38.3°C and 39.5°C respectively.
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ACTIVE_COMPARATOR: Permissive Fever Treatment
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Patients assigned to the permissive treatment strategy will not receive anti-pyretic therapy until the temperature reaches 40.0°C at which point they will receive acetaminophen 650mg every 6 hours.
External cooling will be initiated for temperatures ≥ 40.5°C.
Acetaminophen and external cooling will be discontinued once core temperature is less than 40.0°C and 40.5°C respectively.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
28-day survival
Time Frame: 28-day
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28-day
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Feasibility of randomizing critically ill patients to different fever management strategies
Time Frame: 12 months
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12 months
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Consumption of anti-microbials
Time Frame: Maximum 28-days from enrollment
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Maximum 28-days from enrollment
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Incidence of nosocomial infection
Time Frame: Maximum 28-days from enrollment
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Maximum 28-days from enrollment
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The effect of anti-pyretic treatment of fever on markers of inflammation
Time Frame: 48 hours
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48 hours
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Incidence of myocardial infarction during treatment of fever
Time Frame: Maximum 28-days from enrollment
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Maximum 28-days from enrollment
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Incidence of hepatocellular inflammation related to acetaminophen use
Time Frame: Maximum 28-days from enrollment
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Maximum 28-days from enrollment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kevin Laupland, MD MSc FRCPC, Faculty of Medicine, University of Calgary
- Principal Investigator: Henry T Stelfox, MD PhD FRCPC, Faculty of Medicine, University of Calgary
Publications and helpful links
General Publications
- Niven DJ, Stelfox HT, Leger C, Kubes P, Laupland KB. Assessment of the safety and feasibility of administering antipyretic therapy in critically ill adults: a pilot randomized clinical trial. J Crit Care. 2013 Jun;28(3):296-302. doi: 10.1016/j.jcrc.2012.08.015. Epub 2012 Oct 24.
- Niven DJ, Leger C, Kubes P, Stelfox HT, Laupland KB. Assessment of the safety and feasibility of administering anti-pyretic therapy in critically ill adults: study protocol of a randomized trial. BMC Res Notes. 2012 Mar 16;5:147. doi: 10.1186/1756-0500-5-147.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- E-23090
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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