Anti-pyretic Therapy in Critically Ill Adults
|Fever||Other: Aggressive Fever Treatment Other: Permissive Fever Treatment||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Assessment of the Safety of Anti-pyretic Therapy in Critically Ill Adults|
- 28-day survival [ Time Frame: 28-day ]
- Feasibility of randomizing critically ill patients to different fever management strategies [ Time Frame: 12 months ]
- Consumption of anti-microbials [ Time Frame: Maximum 28-days from enrollment ]
- Incidence of nosocomial infection [ Time Frame: Maximum 28-days from enrollment ]
- The effect of anti-pyretic treatment of fever on markers of inflammation [ Time Frame: 48 hours ]
- Incidence of myocardial infarction during treatment of fever [ Time Frame: Maximum 28-days from enrollment ]
- Incidence of hepatocellular inflammation related to acetaminophen use [ Time Frame: Maximum 28-days from enrollment ]
|Study Start Date:||August 2010|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: Aggressive Fever Treatment||
Other: 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.
|Active Comparator: Permissive Fever Treatment||
Other: Permissive Fever Treatment
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01173367
|Intensive Care Unit, Peter Lougheed Center|
|Calgary, Alberta, Canada, T1Y 6J4|
|Intensive Care Unit, Foothills Medical Center|
|Calgary, Alberta, Canada, T2N 2T9|
|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|