FeverPhase 2NCT01173367
Anti-pyretic Therapy in Critically Ill Adults
A Phase 2 study testing Aggressive Fever Treatment and Permissive Fever Treatment in people with Fever, run by University of Calgary at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fever
- What is being tested?
- Aggressive Fever Treatment and Permissive Fever Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesCanada
- Study dates
- Aug 2010to Jan 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Intensive Care Unit, Peter Lougheed Center
Calgary, Alberta, T1Y 6J4
Intensive Care Unit, Foothills Medical Center
Calgary, Alberta, T2N 2T9
About this study
Official title: Assessment of the Safety of Anti-pyretic Therapy in Critically Ill Adults
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.
Read the 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.
- Conditions
- Fever
- Being tested
- Aggressive Fever Treatment, Permissive Fever Treatment
- Keywords
- Fever, ICU, Acetaminophen, Inflammatory mediators, Safety
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aggressive Fever TreatmentOther
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.
Permissive Fever TreatmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Aggressive Fever Treatment | Active comparator | Not described Receives: Other: Aggressive Fever Treatment |
| Permissive Fever Treatment | Active comparator | Not described Receives: Other: Permissive Fever Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day survival
Measured: 28-day
Secondary outcomes (6)
Feasibility of randomizing critically ill patients to different fever management strategies
Measured: 12 months
Consumption of anti-microbials
Measured: Maximum 28-days from enrollment
Incidence of nosocomial infection
Measured: Maximum 28-days from enrollment
The effect of anti-pyretic treatment of fever on markers of inflammation
Measured: 48 hours
Incidence of myocardial infarction during treatment of fever
Measured: Maximum 28-days from enrollment
Incidence of hepatocellular inflammation related to acetaminophen use
Measured: Maximum 28-days from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Intensive Care Foundation
- Responsible party
- Principal investigator, Daniel Niven, University of Calgary
- Investigators
- Kevin Laupland, MD MSc FRCPC, Principal investigator, Faculty of Medicine, University of CalgaryHenry T Stelfox, MD PhD FRCPC, Principal investigator, Faculty of Medicine, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173367
- Sponsor's protocol ID
- E-23090
- Status last verified
- Feb 2012
- First submitted
- 28 Jul 2010
- Last updated
- 23 Feb 2012
- Results posted
- No
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.
PubMed 23102531Niven 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.
PubMed 22420838
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Safety of Anti-pyretic Therapy in Critically Ill Adults
- ClinicalTrials.gov ID
- NCT01173367
- Acronym / sponsor ID
- E-23090
- Conditions
- Fever
- Keywords
- Fever, ICU, Acetaminophen, Inflammatory mediators, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Intensive Care Foundation
- Study start
- Aug 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 2 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aggressive Fever Treatment | Active comparator | Other: Aggressive Fever Treatment |
| Permissive Fever Treatment | Active comparator | Other: Permissive Fever Treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aggressive Fever TreatmentPatients 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. | Other | Aggressive Fever Treatment |
| Permissive Fever TreatmentPatients 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. | Other | Permissive Fever Treatment |
Primary outcome
28-day survival
Time frame: 28-day
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2012.
- Derived from this study: PubMed 23102531Niven 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.
- Derived from this study: PubMed 22420838Niven 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Laupland, MD MSc FRCPC principal investigator
Faculty of Medicine, University of Calgary
Henry T Stelfox, MD PhD FRCPC principal investigator
Faculty of Medicine, University of Calgary
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aggressive Fever Treatment and Permissive Fever Treatment in people with Fever, run by University of Calgary at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-day survival (time frame: 28-day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01173367, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2012.