The HEAT trial

A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection

Paul J. Young, Manoj K. Saxena, Rinaldo Bellomo, Ross C. Freebairn, Naomi E. Hammond, Frank M.P. van Haren, Seton J. Henderson, Colin J. McArthur, Shay P. McGuinness, Diane Mackle, John A. Myburgh, Mark Weatherall, Steve A.R. Webb, Richard W. Beasley

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15 Citations (Scopus)

Abstract

Background and objective: Paracetamol is commonly administered to febrile critically ill patients with infection. However, there is limited information on the efficacy and safety of using paracetamol in this setting. We describe the study protocol for a Phase IIb multicentre randomised controlled trial (the Permissive Hyperthermia Through Avoidance of Paracetamol in Known or Suspected Infection in ICU [HEAT] trial) comparing intravenous paracetamol to placebo in the treatment of fever in critically ill adults with known or suspected infection. Design and setting: A pilot study followed by the main trial from November 2012. 700 patients will be recruited for concealed, random, parallel assignment of either 1 g of intravenous paracetamol or placebo (100mL of 5% dextrose) 6-hourly to treat fever while they remain on antimicrobial therapy in the intensive care unit. The primary end point will be ICU support-free survival at 28 days after randomisation. Secondary end points will include peak daily and mean daily body temperatures, prevalence of liver dysfunction requiring cessation of study treatment, degree of renal injury (based on delta creatinine), other organ failures, and Day 28 and Day 90 mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: The HEAT trial should generate results that will inform and influence the prescribing of paracetamol. It will also determine if a large-scale Phase III trial of paracetamol is required in this patient group and whether such a trial is feasible. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12612000513819).

Original languageEnglish
Pages (from-to)290-296
Number of pages7
JournalCritical Care and Resuscitation
Volume14
Issue number4
Publication statusPublished - 1 Dec 2012
Externally publishedYes

Cite this

Young, P. J., Saxena, M. K., Bellomo, R., Freebairn, R. C., Hammond, N. E., van Haren, F. M. P., ... Beasley, R. W. (2012). The HEAT trial: A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection. Critical Care and Resuscitation, 14(4), 290-296.
Young, Paul J. ; Saxena, Manoj K. ; Bellomo, Rinaldo ; Freebairn, Ross C. ; Hammond, Naomi E. ; van Haren, Frank M.P. ; Henderson, Seton J. ; McArthur, Colin J. ; McGuinness, Shay P. ; Mackle, Diane ; Myburgh, John A. ; Weatherall, Mark ; Webb, Steve A.R. ; Beasley, Richard W. / The HEAT trial : A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection. In: Critical Care and Resuscitation. 2012 ; Vol. 14, No. 4. pp. 290-296.
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title = "The HEAT trial: A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection",
abstract = "Background and objective: Paracetamol is commonly administered to febrile critically ill patients with infection. However, there is limited information on the efficacy and safety of using paracetamol in this setting. We describe the study protocol for a Phase IIb multicentre randomised controlled trial (the Permissive Hyperthermia Through Avoidance of Paracetamol in Known or Suspected Infection in ICU [HEAT] trial) comparing intravenous paracetamol to placebo in the treatment of fever in critically ill adults with known or suspected infection. Design and setting: A pilot study followed by the main trial from November 2012. 700 patients will be recruited for concealed, random, parallel assignment of either 1 g of intravenous paracetamol or placebo (100mL of 5{\%} dextrose) 6-hourly to treat fever while they remain on antimicrobial therapy in the intensive care unit. The primary end point will be ICU support-free survival at 28 days after randomisation. Secondary end points will include peak daily and mean daily body temperatures, prevalence of liver dysfunction requiring cessation of study treatment, degree of renal injury (based on delta creatinine), other organ failures, and Day 28 and Day 90 mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: The HEAT trial should generate results that will inform and influence the prescribing of paracetamol. It will also determine if a large-scale Phase III trial of paracetamol is required in this patient group and whether such a trial is feasible. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12612000513819).",
author = "Young, {Paul J.} and Saxena, {Manoj K.} and Rinaldo Bellomo and Freebairn, {Ross C.} and Hammond, {Naomi E.} and {van Haren}, {Frank M.P.} and Henderson, {Seton J.} and McArthur, {Colin J.} and McGuinness, {Shay P.} and Diane Mackle and Myburgh, {John A.} and Mark Weatherall and Webb, {Steve A.R.} and Beasley, {Richard W.}",
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Young, PJ, Saxena, MK, Bellomo, R, Freebairn, RC, Hammond, NE, van Haren, FMP, Henderson, SJ, McArthur, CJ, McGuinness, SP, Mackle, D, Myburgh, JA, Weatherall, M, Webb, SAR & Beasley, RW 2012, 'The HEAT trial: A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection', Critical Care and Resuscitation, vol. 14, no. 4, pp. 290-296.

The HEAT trial : A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection. / Young, Paul J.; Saxena, Manoj K.; Bellomo, Rinaldo; Freebairn, Ross C.; Hammond, Naomi E.; van Haren, Frank M.P.; Henderson, Seton J.; McArthur, Colin J.; McGuinness, Shay P.; Mackle, Diane; Myburgh, John A.; Weatherall, Mark; Webb, Steve A.R.; Beasley, Richard W.

In: Critical Care and Resuscitation, Vol. 14, No. 4, 01.12.2012, p. 290-296.

Research output: Contribution to journalArticleOtherpeer-review

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T1 - The HEAT trial

T2 - A protocol for a multicentre randomised placebo-controlled trial of IV paracetamol in ICU patients with fever and infection

AU - Young, Paul J.

AU - Saxena, Manoj K.

AU - Bellomo, Rinaldo

AU - Freebairn, Ross C.

AU - Hammond, Naomi E.

AU - van Haren, Frank M.P.

AU - Henderson, Seton J.

AU - McArthur, Colin J.

AU - McGuinness, Shay P.

AU - Mackle, Diane

AU - Myburgh, John A.

AU - Weatherall, Mark

AU - Webb, Steve A.R.

AU - Beasley, Richard W.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Background and objective: Paracetamol is commonly administered to febrile critically ill patients with infection. However, there is limited information on the efficacy and safety of using paracetamol in this setting. We describe the study protocol for a Phase IIb multicentre randomised controlled trial (the Permissive Hyperthermia Through Avoidance of Paracetamol in Known or Suspected Infection in ICU [HEAT] trial) comparing intravenous paracetamol to placebo in the treatment of fever in critically ill adults with known or suspected infection. Design and setting: A pilot study followed by the main trial from November 2012. 700 patients will be recruited for concealed, random, parallel assignment of either 1 g of intravenous paracetamol or placebo (100mL of 5% dextrose) 6-hourly to treat fever while they remain on antimicrobial therapy in the intensive care unit. The primary end point will be ICU support-free survival at 28 days after randomisation. Secondary end points will include peak daily and mean daily body temperatures, prevalence of liver dysfunction requiring cessation of study treatment, degree of renal injury (based on delta creatinine), other organ failures, and Day 28 and Day 90 mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: The HEAT trial should generate results that will inform and influence the prescribing of paracetamol. It will also determine if a large-scale Phase III trial of paracetamol is required in this patient group and whether such a trial is feasible. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12612000513819).

AB - Background and objective: Paracetamol is commonly administered to febrile critically ill patients with infection. However, there is limited information on the efficacy and safety of using paracetamol in this setting. We describe the study protocol for a Phase IIb multicentre randomised controlled trial (the Permissive Hyperthermia Through Avoidance of Paracetamol in Known or Suspected Infection in ICU [HEAT] trial) comparing intravenous paracetamol to placebo in the treatment of fever in critically ill adults with known or suspected infection. Design and setting: A pilot study followed by the main trial from November 2012. 700 patients will be recruited for concealed, random, parallel assignment of either 1 g of intravenous paracetamol or placebo (100mL of 5% dextrose) 6-hourly to treat fever while they remain on antimicrobial therapy in the intensive care unit. The primary end point will be ICU support-free survival at 28 days after randomisation. Secondary end points will include peak daily and mean daily body temperatures, prevalence of liver dysfunction requiring cessation of study treatment, degree of renal injury (based on delta creatinine), other organ failures, and Day 28 and Day 90 mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: The HEAT trial should generate results that will inform and influence the prescribing of paracetamol. It will also determine if a large-scale Phase III trial of paracetamol is required in this patient group and whether such a trial is feasible. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12612000513819).

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