Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults (ICUFeverAPAP)

July 11, 2017 updated by: University of California, San Francisco

Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: a Randomized Controlled Trial

The purpose of this study is to compare the effects of intravenous acetaminophen to placebo on body temperature and hemodynamic (heart rate and blood pressure) responses in febrile critically ill adult patients.

There are limited data to explain the variable and unpredictable antipyretic and hemodynamic response to acetaminophen in febrile ICU patients. The complex pathophysiology of critically ill patients, co-morbid conditions, the effect of multiple pharmacologic and non-pharmacologic care interventions, and/or the potential interferences with absorption of enteral or rectal formulations may be related to variations in the antipyretic response to acetaminophen. It is necessary for clinicians to have a better understanding of the therapy response and potential adverse effects of this commonly administered medication, especially the recently available IV formulation, in critically ill patients. Further research of the antipyretic response to acetaminophen in critically ill patients is warranted to inform evidence-based practice guidelines for fever management. Further randomized, placebo-controlled studies of hemodynamic responses to IV acetaminophen are also warranted.

Primary Hypothesis:

There is a significant reduction in time-weighted average core body temperature over 4 hours after administration of IV acetaminophen compared to placebo in febrile critically ill patients.

Secondary Hypotheses:

  1. There is a significant reduction in time-weighted average heart rate over 4 hours after administration of IV acetaminophen compared to placebo in febrile critically ill patients.
  2. There is a significant reduction in time-weighted mean arterial pressure over 4 hours after administration of IV acetaminophen compared to placebo in febrile critically ill patients.

Adult patients with fever (≥ 38.3ºCentigrade/101ºFarenheit) in the intensive care unit will be screened for eligibility and enrolled after informed consent. Patients will be randomized to receive IV acetaminophen 1 gram or normal saline 100 mLs. Body temperature, heart rate, and blood pressure will be measured at baseline and during the 4 hours post study drug administration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Adult patients with fever (≥ 38.3ºCentigrade (C)/101ºFarenheit(F)) in the intensive care unit will be screened for eligibility and approached for informed consent. Enrolled patients will be stratified based on the leading etiology of their fever: either neurologic injury or infection and then randomized to receive IV acetaminophen 1 gram or normal saline 100 milliliters (mLs). Core body temperature will be measured using a zero-heat flow thermometry system (non-invasive, small disk on forehead). Patients will be monitored and data collected during the 4-hour post study drug administration period. A rescue protocol will be implemented if the temperature reaches ≥ 40 ºC during the study period and includes notification of primary team provider by the nurse and the pharmacist will contact them to inform the provider of study group (acetaminophen or placebo). The provider can decide whether to order antipyretic medication or physical cooling interventions at that time.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years of age and older
  • Patient in an intensive care unit
  • Weight greater or equal to 50 kgs
  • Fever: core body temperature greater than or equal to 38.3 degrees Celsius
  • Clinically stable: no active resuscitation with fluids, blood products, or dose increases of vasoactive medications within 1 hour of study drug administration

Exclusion Criteria:

  • Acetaminophen hypersensitivity
  • Acute liver failure or acute liver injury
  • Heat stroke, malignant hyperthermia, neuroleptic malignant syndrome
  • Therapeutic cooling, physical cooling, extracorporeal blood circuit therapies
  • Administration of acetaminophen-containing medications, non-steroidal anti-inflammatory drugs, or aspirin greater than 81 mg within specified times per drug prior to fever presentation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Normal saline placebo
Normal saline 100 mLs intravenous, administered over 15 minutes
Drug: Placebo
Normal saline placebo Normal saline 100 mLs intravenous, administered over 15 minutes
Other Names:
  • NS
  • 0.9% sodium chloride
Experimental: Acetaminophen
Acetaminophen 1 gram/100 mLs intravenous, single dose administered over 15 minutes
Drug: Acetaminophen
acetaminophen 1 gram/100mLs intravenously administered over 15 minutes
Other Names:
  • Ofirmev

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Core Body Temperature
Time Frame: Baseline to 4 hours post study drug administration
time-weighted average core body temperature over 4 hours. Core temperature was measured every 5 minutes times 4, and then every 15 minutes over the following 4 hours from the time of study drug administration. The sum of the core temperature values was divided by time in minutes.
Baseline to 4 hours post study drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart Rate
Time Frame: Baseline to 4 hours post study drug administration
time-weighted average heart rate over 4 hours. Heart rate was measured every 5 minutes times 4, and then every 15 minutes over the following 4 hours from the time of study drug administration. The sum of the heart rate values was divided by time in minutes.
Baseline to 4 hours post study drug administration
Systolic Blood Pressure
Time Frame: Baseline to 4 hours post study drug administration
time-weighted average systolic blood pressure over 4 hours. Systolic blood pressure was measured every 5 minutes times 4, and then every 15 minutes over the following 4 hours from the time of study drug administration. The sum of the systolic blood pressure values was divided by time in minutes.
Baseline to 4 hours post study drug administration
Respiratory Rate
Time Frame: Baseline to 4 hours post study drug administration
time weighted average for respiratory rate over 4 hours. Respiratory rate was measured every 5 minutes times 4, and then every 15 minutes over the following 4 hours from the time of study drug administration. The sum of the respiratory rate values was divided by time in minutes.
Baseline to 4 hours post study drug administration
2-hour Change Over Time Core Temperature
Time Frame: 2 hours
change over time core temperature after study drug administration (adjusted to baseline core temperature)
2 hours
2-hour Change Over Time Systolic Blood Pressure
Time Frame: Baseline to 2 hours
2-hour change over time SBP from study drug administration (means adjusted to baseline SBP)
Baseline to 2 hours
2-hour Change Over Time Heart Rate
Time Frame: Baseline to 2 hours
2-hour change over time heart rate from time of study drug administration (means adjusted to baseline HR)
Baseline to 2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Kathleen A. Puntillo, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

May 31, 2013

First Submitted That Met QC Criteria

June 4, 2013

First Posted (Estimate)

June 5, 2013

Study Record Updates

Last Update Posted (Actual)

August 9, 2017

Last Update Submitted That Met QC Criteria

July 11, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSF-ICUFever

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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