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

NCT ID: NCT01869699

Last Updated: 2017-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2015-08-31

Brief Summary

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.

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.

Conditions

Fever; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Normal saline placebo

Normal saline 100 mLs intravenous, administered over 15 minutes

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline placebo Normal saline 100 mLs intravenous, administered over 15 minutes

Acetaminophen

Acetaminophen 1 gram/100 mLs intravenous, single dose administered over 15 minutes

Group Type: EXPERIMENTAL

Acetaminophen

Intervention Type: DRUG

acetaminophen 1 gram/100mLs intravenously administered over 15 minutes

Interventions

Acetaminophen

acetaminophen 1 gram/100mLs intravenously administered over 15 minutes

Intervention Type: DRUG

Placebo

Normal saline placebo Normal saline 100 mLs intravenous, administered over 15 minutes

Intervention Type: DRUG

Other Intervention Names

Ofirmev; NS; 0.9% sodium chloride

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathleen A. Puntillo, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Medical Center

San Francisco, California, United States

University of California, San Francisco Medical Center

San Francisco, California, United States

Countries

United States

References

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Other Identifiers

UCSF-ICUFever

Identifier Type: -

Identifier Source: org_study_id