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

NCT01869699 | Completed Phase 4 Results DMC

• 1 other identifier: UCSF-ICUFever
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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. 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. 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.

Conditions

Fever; Critical Illness

Keywords

Fever; Acetaminophen; Critical Care; ICU; Febrile

Outcome Measures

Primary Outcomes (1)

• Core Body Temperature

  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 Outcomes (6)

• Heart Rate

  Baseline to 4 hours post study drug administration

• Systolic Blood Pressure

  Baseline to 4 hours post study drug administration

• Respiratory Rate

  Baseline to 4 hours post study drug administration

• 2-hour Change Over Time Core Temperature

  2 hours

• 2-hour Change Over Time Systolic Blood Pressure

  Baseline to 2 hours

Study Arms (2)

Normal saline placebo

PLACEBO COMPARATOR

Normal saline 100 mLs intravenous, administered over 15 minutes

Drug: Placebo

Acetaminophen

EXPERIMENTAL

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

Drug: Acetaminophen

Interventions

Acetaminophen DRUG

acetaminophen 1 gram/100mLs intravenously administered over 15 minutes

Also known as: Ofirmev

Acetaminophen

Placebo DRUG

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

Also known as: NS, 0.9% sodium chloride

Normal saline placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (2)

UCSF Medical Center

San Francisco, California, 94143, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Related Publications (13)

• Laupland KB, Zahar JR, Adrie C, Schwebel C, Goldgran-Toledano D, Azoulay E, Garrouste-Orgeas M, Cohen Y, Jamali S, Souweine B, Darmon M, Timsit JF. Determinants of temperature abnormalities and influence on outcome of critical illness. Crit Care Med. 2012 Jan;40(1):145-51. doi: 10.1097/CCM.0b013e31822f061d.

  PMID: 21926588 BACKGROUND

• Lee BH, Inui D, Suh GY, Kim JY, Kwon JY, Park J, Tada K, Tanaka K, Ietsugu K, Uehara K, Dote K, Tajimi K, Morita K, Matsuo K, Hoshino K, Hosokawa K, Lee KH, Lee KM, Takatori M, Nishimura M, Sanui M, Ito M, Egi M, Honda N, Okayama N, Shime N, Tsuruta R, Nogami S, Yoon SH, Fujitani S, Koh SO, Takeda S, Saito S, Hong SJ, Yamamoto T, Yokoyama T, Yamaguchi T, Nishiyama T, Igarashi T, Kakihana Y, Koh Y; Fever and Antipyretic in Critically ill patients Evaluation (FACE) Study Group. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Crit Care. 2012 Feb 28;16(1):R33. doi: 10.1186/cc11211.

  PMID: 22373120 BACKGROUND

• Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT. Occurrence and outcome of fever in critically ill adults. Crit Care Med. 2008 May;36(5):1531-5. doi: 10.1097/CCM.0b013e318170efd3.

  PMID: 18434882 BACKGROUND

• Circiumaru B, Baldock G, Cohen J. A prospective study of fever in the intensive care unit. Intensive Care Med. 1999 Jul;25(7):668-73. doi: 10.1007/s001340050928.

  PMID: 10470569 BACKGROUND

• Frankenfield DC, Smith JS Jr, Cooney RN, Blosser SA, Sarson GY. Relative association of fever and injury with hypermetabolism in critically ill patients. Injury. 1997 Nov-Dec;28(9-10):617-21. doi: 10.1016/s0020-1383(97)00117-4.

  PMID: 9624339 BACKGROUND

• Thompson HJ, Kagan SH. Clinical management of fever by nurses: doing what works. J Adv Nurs. 2011 Feb;67(2):359-70. doi: 10.1111/j.1365-2648.2010.05506.x. Epub 2010 Nov 2.

  PMID: 21044137 BACKGROUND

• Niven DJ, Stelfox HT, Laupland KB. Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis. J Crit Care. 2013 Jun;28(3):303-10. doi: 10.1016/j.jcrc.2012.09.009. Epub 2012 Nov 14.

  PMID: 23159136 BACKGROUND

• de Maat MM, Tijssen TA, Bruggemann RJ, Ponssen HH. Paracetamol for intravenous use in medium--and intensive care patients: pharmacokinetics and tolerance. Eur J Clin Pharmacol. 2010 Jul;66(7):713-9. doi: 10.1007/s00228-010-0806-5. Epub 2010 Mar 19.

  PMID: 20300741 BACKGROUND

• Kett DH, Breitmeyer JB, Ang R, Royal MA. A randomized study of the efficacy and safety of intravenous acetaminophen vs. intravenous placebo for the treatment of fever. Clin Pharmacol Ther. 2011 Jul;90(1):32-9. doi: 10.1038/clpt.2011.98. Epub 2011 May 4.

  PMID: 21544074 BACKGROUND

• Mackenzie I, Forrest K, Thompson F, Marsh R. Effects of acetaminophen administration to patients in intensive care. Intensive Care Med. 2000 Sep;26(9):1408. doi: 10.1007/s001340000614. No abstract available.

  PMID: 11089781 BACKGROUND

• Boyle M, Hundy S, Torda TA. Paracetamol administration is associated with hypotension in the critically ill. Aust Crit Care. 1997 Dec;10(4):120-2. doi: 10.1016/s1036-7314(97)70414-4.

  PMID: 9708071 BACKGROUND

• Boyle M, Nicholson L, O'Brien M, Flynn GM, Collins DW, Walsh WR, Bihari D. Paracetamol induced skin blood flow and blood pressure changes in febrile intensive care patients: An observational study. Aust Crit Care. 2010 Nov;23(4):208-14. doi: 10.1016/j.aucc.2010.06.004. Epub 2010 Jul 22.

  PMID: 20655241 BACKGROUND

• Hersch M, Raveh D, Izbicki G. Effect of intravenous propacetamol on blood pressure in febrile critically ill patients. Pharmacotherapy. 2008 Oct;28(10):1205-10. doi: 10.1592/phco.28.10.1205.

  PMID: 18823215 BACKGROUND

MeSH Terms

Conditions

Fever; Critical Illness

Interventions

Acetaminophen; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The generalizability of our findings is limited due to the use of a single site and our sample size was modest. Also, patients in this study had baseline stable and normal or high BP, so unclear if same results in patients with unstable or low BP.

Results Point of Contact

• Title: Dr. Hildy Schell-Chaple
• Organization: University of California, San Francisco

hildegarde.schell-chaple@ucsf.edu

415-353-1039

Study Officials

• Kathleen A. Puntillo, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2013
• First Posted: June 5, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 9, 2017
• Results First Posted: August 9, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)