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Trial record 64 of 1880 for:    ACETAMINOPHEN

Safety and Efficacy of Acetaminophen in the Intensive Care Unit. (SEA-ICU)

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ClinicalTrials.gov Identifier: NCT02280239
Recruitment Status : Terminated (Only enrolled 10 participants over 9 months which is less then anticipated (75).)
First Posted : October 31, 2014
Last Update Posted : May 20, 2016
Sponsor:
Collaborator:
Vancouver Coastal Health Research Institute
Information provided by (Responsible Party):
University of British Columbia

Brief Summary:

The intensive care unit (ICU) team needs to know what effects acetaminophen has in critically ill patients. Acetaminophen is better known as Tylenol. It is the drug given to reduce fever. Most research that has looked at how safe and effective this drug is, has been done with healthy people. Those studies tell us it is safe and works well to bring down fever.

This may not be true for the ICU patient. Some research found acetaminophen was not as good at reducing fever as expected in the ICU. Fever helps to fight infection so it may help patients get better, but it is also stressful. When you have fever, you to need more oxygen, and your heart beats faster. If you have a fever after brain injury, you are less likely to make a full recovery. In patients with brain injury, a weak heart or trouble breathing we should treat fever. If we can predict how well acetaminophen will reduce fever, we can decide if this drug is enough, or other treatments are also needed.

If you do not have problems with your brain, heart, or lungs, it is safe to not treat fever. When you give this drug to treat fever, the body cools itself by sweating, and bringing hot blood to the skin's surface. These changes do not affect healthy people. Research suggests ICU patients may be at risk for sudden drop in blood pressure.

Our study will answer 2 questions: 1) When acetaminophen is given to treat fever in ICU patients, are they more likely to have a drop in blood pressure? 2) How much will acetaminophen reduce fever in ICU patients? We will study ICU patients with a fever who can safely get, or not get this drug. This information will help us decide when and how to treat fever in the ICU.


Condition or disease Intervention/treatment Phase
Critical Illness Fever Drug: Acetaminophen Drug: Placebo Phase 4

Detailed Description:

In the ICU, fever is commonly treated with 650 mg acetaminophen every 4 hours with the hopes of reducing fever burden, thereby also reducing metabolic demand. Acetaminophen is thought to be a safe and effective antipyretic. This assumption has not been tested in the critically ill despite its widespread use. Observational studies report critically ill patients experience hypotension, sometimes severe enough to require treatment; other studies indicate acetaminophen may not be as effective at reducing fever burden in the critically ill.

OBJECTIVES:

  • To see if 650mg acetaminophen, given to febrile critically ill patients affects blood pressure; by comparing the incidence of hypotension severe enough to require treatment in the way of a fluid bolus (500cc or greater) or increase in vasoactive drugs (increase in norepinephrine by 5mcg or greater); by assessing for changes in mean arterial pressure and systolic blood pressure.
  • To quantify the degree of fever suppression achieved by 650mg acetaminophen in the febrile critically ill population.

RESEARCH PROPOSAL:

Patients admitted into Vancouver Hospital's ICU are eligible for this study if they have a new fever and meet the inclusion/exclusion criteria. Study participants will be randomly assigned into one of 2 study arms, the control group and the 650mg group. Study participants in the control group will receive 2 capsules of placebo and the 650mg group will receive 2 capsules of 325mg acetaminophen. Data (continuous measures of temperature, heart rate and blood pressure) will be collected from the time of the study drug administration until 6 hours post. All patients, health care workers, and researchers will be blinded to which arm the patient is enrolled in until the end of the study. The incidence of fluid bolus administration, increases in vasoactive drug use, will be recorded and compared. We will also compare blood pressure data, and fever burden between the 2 groups.

INCLUSION/EXCLUSION CRITERIA To be included the subject must be admitted to the ICU; have an arterial line as standard of care; have at least 2 hours of a temperature greater than 38.3°C; within 24 hours of fever onset or ICU admission; be hemodynamically stable, and not received any drugs with known antipyretic effects at least 6 hours prior to initiating the study. Patients are excluded if they have an acute brain injury, liver dysfunction, cardiac dysfunction, requiring greater than 50% fraction of inspired oxygen (FiO); mechanical ventilation is permitted, any extracorporeal blood treatments (dialysis, plasmapheresis, etc.), injury to more than 20% of the skin (i.e. burn patient), or the responsible physician is opposed to enrolment.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Antipyretic Efficacy of Acetaminophen in the Febrile Intensive Care Unit Patient.
Study Start Date : May 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Control Group
This group consists of stable but febrile ICU patients (temp >38.3°C). Participants in this group will receive a one-time dose of placebo via the enteral route (via the gut), after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
Drug: Placebo
one-time dose of placebo (identical capsule) given via the enteral route (via the gut)
Other Name: Pharmacy compounded look alike capsule to the study drug

Experimental: Acetaminophen Group
This group consists of stable but febrile ICU patients (temp >38.3°C). Participants in this group will receive a one-time does of acetaminophen 650mg via the enteral route (via the gut), after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
Drug: Acetaminophen
one-time dose of acetaminophen 650mg given via the enteral route (via the gut)
Other Name: Tylenol




Primary Outcome Measures :
  1. Clinically Significant Hypotension [ Time Frame: 4 hours post acetaminophen administration ]
    Clinically significant hypotension is defined as an acute drop in mean arterial pressure requiring treatment. Treatment is defined as either a 500 cc (or greater) fluid bolus and/or an increase in inotrope support of greater than 5 mcg/min over baseline.


Secondary Outcome Measures :
  1. Blood Pressure [ Time Frame: 4 hours post intervention ]
    systolic, diastolic and mean arterial pressures will be monitored for 4 hours post intervention

  2. Equivalent-dose of vasoactive medication post intervention [ Time Frame: 4 hours post intervention ]
    Total dose of all vasoactive medications will be converted to total Equidose value (with the formula 10 mcg/min norepinephrine ≈ 5 mcg/kg/min dopamine ≈ 10 mcg/min epinephrine ≈ 1 mcg/min phenylephrine ≈ 0.02 u/min vasopressin as per Russell et al. (2008)) before comparing the treatment and control groups

  3. Equivalent-volume Fluid administered post intervention [ Time Frame: 4 hours post intervention ]
    Total crystalloid and colloid fluid will be converted the the equi-volume dose (with the ratio 1.4:1 (as per Finfer et al.(2004) & Vincent and Weil (2006) before making comparisons between the treatment and control groups

  4. Fever Burden [ Time Frame: 6 hours post intervention ]
    Continuous measurements of core body temperature will be recorded for 6 hours. Fever burden is defined as area between the 6 hour temperature curve and 38.3°C cut-off.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Generally to be considered for this study one must be critically ill, febrile, and can safely either receive acetaminophen or have acetaminophen withheld. Also one must not have conditions that would alter normal drug absorption or normal thermoregulation. Specifically the eligibility criteria are:

INCLUSION CRITERIA:

  • Adult patients (> 18 years) admitted to Intensive Care Unit at Vancouver Hospital with a core temperature > 38.3 °C for 2 or more consecutive hours, but not longer than 48 hours*
  • Continuous arterial pressure monitor in place at the time of intervention and data collection
  • Patients may only participate in the study once
  • To remain in the ICU for the entire study period (2 hours prior to drug administration to 4 hours post drug administration)

EXCLUSION CRITERIA:

  • Significant liver dysfunction
  • Acute neurological injury
  • Seizure disorder
  • Cardiomyopathy, elevated cardiac enzymes indicative of an acute cardiac injury, electrocardiogram (ECG) changes indicative of cardiac ischemia (i.e., ST segment elevation/depression)
  • Hemodynamic instability (requiring fluid boluses, or change/initiation of vasopressors. Patients receiving steady doses of vasopressor support may be included)
  • Severe hypoxemia, (fraction of inspired oxygen (FiO2) requirements of more than 60% to maintain hemoglobin oxygen saturation (SaO2) > 90% or partial pressure of oxygen in the blood (PaO2) > 70)
  • Temperature > 40.0 °C
  • Receiving external cooling
  • Haemodialysis, plasma exchange, or any treatment where the blood is taken out of the body and processed
  • Acute thermal injury to skin (i.e., burn)
  • Gut malabsorption (i.e., receiving < 40% required calories enterally)
  • Receiving medications that have known antipyretic effects (acetaminophen, ibuprofen, steroids, etc.)
  • Physician opposed to enrolment in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02280239


Locations
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Canada, British Columbia
Vancouver Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Sponsors and Collaborators
University of British Columbia
Vancouver Coastal Health Research Institute
Investigators
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Study Chair: William Henderson, PhD University of British Columbia
Principal Investigator: Vininder K Bains, BSN Vancouver Coastal Health
Study Chair: Martha Mackay, PhD University of British Columbia
Study Chair: Leanne Currie, PhD University of British Columbia

Publications:

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Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT02280239     History of Changes
Other Study ID Numbers: H13-01160
First Posted: October 31, 2014    Key Record Dates
Last Update Posted: May 20, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Under review with the research team.
Keywords provided by University of British Columbia:
Fever
Acetaminophen
Body Temperature Regulation
Critical Illness
Hypotension
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics