Anti-pyretic Therapy in Critically Ill Adults

NCT01173367 | Completed Phase 2

• 1 other identifier: E-23090
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Fever

Keywords

Fever; ICU; Acetaminophen; Inflammatory mediators; Safety

Outcome Measures

Primary Outcomes (1)

• 28-day survival

  28-day

Secondary Outcomes (6)

• Feasibility of randomizing critically ill patients to different fever management strategies

  12 months

• Consumption of anti-microbials

  Maximum 28-days from enrollment

• Incidence of nosocomial infection

  Maximum 28-days from enrollment

• The effect of anti-pyretic treatment of fever on markers of inflammation

  48 hours

• Incidence of myocardial infarction during treatment of fever

  Maximum 28-days from enrollment

Study Arms (2)

Aggressive Fever Treatment

ACTIVE COMPARATOR

Other: Aggressive Fever Treatment

Permissive Fever Treatment

ACTIVE COMPARATOR

Other: Permissive Fever Treatment

Interventions

Aggressive Fever Treatment OTHER

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.

Aggressive Fever Treatment

Permissive Fever Treatment OTHER

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.

Permissive Fever Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Canadian Intensive Care Foundation: collaborator

Study Sites (2)

Intensive Care Unit, Peter Lougheed Center

Calgary, Alberta, T1Y 6J4, Canada

Location

Intensive Care Unit, Foothills Medical Center

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (2)

• 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.

  PMID: 23102531 DERIVED

• 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.

  PMID: 22420838 DERIVED

MeSH Terms

Conditions

Fever

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Intensivist, Department of Critical Care Medicine

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: August 2, 2010
• Study Start: August 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: February 23, 2012

Record last verified: 2012-02

Locations

CA (2)