Anti-pyretic Therapy in Critically Ill Adults

This study has been completed.
Sponsor:
Collaborator:
Canadian Intensive Care Foundation
Information provided by (Responsible Party):
Daniel Niven, University of Calgary
ClinicalTrials.gov Identifier:
NCT01173367
First received: July 28, 2010
Last updated: February 21, 2012
Last verified: February 2012
  Purpose

The impact of fever and its management in different medical and surgical populations of critically ill patients has not been explained to date. The current study aims to assess the safety and efficacy of treatment of critically ill patients with a permissive versus aggressive fever treatment strategy.


Condition Intervention Phase
Fever
Other: Aggressive Fever Treatment
Other: Permissive Fever Treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Assessment of the Safety of Anti-pyretic Therapy in Critically Ill Adults

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 28-day survival [ Time Frame: 28-day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Feasibility of randomizing critically ill patients to different fever management strategies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Consumption of anti-microbials [ Time Frame: Maximum 28-days from enrollment ] [ Designated as safety issue: No ]
  • Incidence of nosocomial infection [ Time Frame: Maximum 28-days from enrollment ] [ Designated as safety issue: Yes ]
  • The effect of anti-pyretic treatment of fever on markers of inflammation [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Incidence of myocardial infarction during treatment of fever [ Time Frame: Maximum 28-days from enrollment ] [ Designated as safety issue: Yes ]
  • Incidence of hepatocellular inflammation related to acetaminophen use [ Time Frame: Maximum 28-days from enrollment ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: August 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01173367

Locations
Canada, Alberta
Intensive Care Unit, Peter Lougheed Center
Calgary, Alberta, Canada, T1Y 6J4
Intensive Care Unit, Foothills Medical Center
Calgary, Alberta, Canada, T2N 2T9
Sponsors and Collaborators
University of Calgary
Canadian Intensive Care Foundation
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
  More Information

No publications provided by University of Calgary

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Niven, Intensivist, Department of Critical Care Medicine, University of Calgary
ClinicalTrials.gov Identifier: NCT01173367     History of Changes
Other Study ID Numbers: E-23090
Study First Received: July 28, 2010
Last Updated: February 21, 2012
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
Fever
ICU
Acetaminophen
Inflammatory mediators
Safety

Additional relevant MeSH terms:
Critical Illness
Disease Attributes
Pathologic Processes
Acetaminophen
Antipyretics
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014