Safety and Efficacy of Acetaminophen in the Intensive Care Unit.

NCT02280239 | Terminated Phase 4 Results

• 1 other identifier: H13-01160
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Illness; Fever

Keywords

Fever; Acetaminophen; Body Temperature Regulation; Critical Illness; Hypotension

Outcome Measures

Primary Outcomes (1)

• Clinically Significant Hypotension

  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.

  4 hours post acetaminophen administration

Secondary Outcomes (4)

• Blood Pressure

  4 hours post intervention

• Equivalent-dose of Vasoactive Medication Post Intervention

  4 hours post intervention

• Equivalent-volume Fluid Administered Post Intervention

  4 hours post intervention

• Fever Burden

  6 hours post intervention

Study Arms (2)

Control Group

PLACEBO COMPARATOR

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

Acetaminophen Group

EXPERIMENTAL

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

Interventions

Acetaminophen DRUG

one-time dose of acetaminophen 650mg given via the enteral route (via the gut)

Also known as: Tylenol

Acetaminophen Group

Placebo DRUG

one-time dose of placebo (identical capsule) given via the enteral route (via the gut)

Also known as: Pharmacy compounded look alike capsule to the study drug

Control Group

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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
• patients no longer needed to recieve 40% of required calories enterally, instead patients who were not receiving any caloric intake via the gut could be enrolled as long as they were still permitted to receive oral medications.
• patients no longer had to have acetaminophen discontinued upon enrollment. They could not be receiving it regularly but could still receive acetaminophen on an as needed (PRN) basis as long as it could be safely withheld for up to 12 hours if they developed a fever.

Sponsors & Collaborators

• University of British Columbia: lead
• Vancouver Coastal Health Research Institute: collaborator

Study Sites (1)

Vancouver Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (16)

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  PMID: 20655241 BACKGROUND

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  PMID: 19781895 BACKGROUND

MeSH Terms

Conditions

Critical Illness; Fever; Hypotension

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Body Temperature Changes; Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Vininder Kour Bains
• Organization: Providence Health Care

VBains@providencehealth.bc.ca

604-682-2344

Study Officials

• William Henderson, PhD

  University of British Columbia

  STUDY CHAIR

• Vininder K Bains, BSN

  Vancouver Coastal Health

  PRINCIPAL INVESTIGATOR

• Martha Mackay, PhD

  University of British Columbia

  STUDY CHAIR

• Leanne Currie, PhD

  University of British Columbia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: May 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: November 4, 2022
• Results First Posted: November 4, 2022

Record last verified: 2022-11

Locations

CA (1)