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The Paracetamol AfteR Traumatic Brain InjurY Study (PARITY)

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ClinicalTrials.gov Identifier: NCT01231139
Recruitment Status : Completed
First Posted : November 1, 2010
Last Update Posted : October 28, 2014
Sponsor:
Collaborators:
The George Institute
The University of New South Wales
Royal Brisbane and Women's Hospital
Information provided by (Responsible Party):
Dr. M.K. Saxena, South East Sydney and Illawarra Area Health Service

Brief Summary:
This primary aim is to investigate the effect of paracetamol in reducing body temperature in patients who have sustained traumatic brain injury. This study is also investigating the safety of paracetamol in this patient population.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Paracetamol Drug: 0.9% Sodium Chloride Schedule: Phase 2

Detailed Description:

Traumatic head injury is a bruising of areas of the brain that occurs commonly as a result of a fall or a motor vehicle accident. Unfortunately, this is a common global occurrence and it occurs both in developing and developed countries. It causes death in nearly 1 in 3 of those who are most severely affected and a large proportion of those that survive have long-term physical or mental disability. Hence, traumatic head injury is a major global problem.

At present there are very few therapies that are known to be effective after a traumatic head injury. In particular the investigators are uncertain about whether modifying body temperature has any effect (good or bad) on the outcomes of patients. Although, this is practiced by some intensive care units around the world.

The investigators have searched extensively to look for any evidence that altering body temperature after traumatic head injury improves the outcome of patients (by reducing the amount of death or disability) and were unable to find any evidence at all. Some preliminary research in both animal experiments and clinical studies suggest that a raised temperature after forms of brain injury may in fact be harmful.

Therefore, at present the investigators believe that we do not really know what effect changing body temperature after head injury has on the outcome of patients.

The investigators are proposing to conduct a clinical study of patients who have had a severe head injury. The patients will be randomly allocated to 2 groups who will get either regular Paracetamol (dissolved in fluid) or a bottle of fluid without any Paracetamol. The 2 treatments will look identical and neither the patients nor the health care workers will know what treatment they are getting. Doing the study in this way will allow us to work out whether giving Paracetamol reduces the temperature of the body and whether there are any side effects that occur. If the study shows that Paracetamol can reduce body temperature safely in this setting then the investigators will work towards doing a larger study of treatments that reduce body temperature. The purpose of this larger study would be to see if the investigators can, not only reduce body temperature but also reduce amount of disability (physical and mental) as well as the death rate in traumatically brain injured patients.

In the proposed study the investigators will be using a higher dose of Paracetamol that is usually prescribed. Other research has shown that the dose that the investigators are proposing to use is safe and also that smaller doses in fact do not reduce body temperature.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre Phase 2b Randomised Controlled Trial Investigating the Efficacy and Safety of Intravenous Paracetamol in Reducing Core Body Temperature After Traumatic Brain Injury
Study Start Date : October 2010
Actual Primary Completion Date : December 2013
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Paracetamol
Paracetamol dissolved in 0.9% Sodium Chloride
Drug: Paracetamol
Intravenous paracetamol, 1 gram (100mls), administered over 30 minutes (every 4 hours for 3 days).
Other Name: Perfalgan

Placebo Comparator: 0.9% Sodium Chloride
0.9% Sodium Chloride
Drug: 0.9% Sodium Chloride Schedule:
Identical placebo: 100mls saline given intravenous over 30 minutes (every 4 hours for 3 days)
Other Name: Saline




Primary Outcome Measures :
  1. Core body temperature: bladder temperature probe [ Time Frame: 30 minutes after final dose of study drug has been administered ]

Secondary Outcome Measures :
  1. Blood Pressure (systolic and mean arterial pressure) measured by intra-arterial pressure monitor [ Time Frame: 6 hourly during study treatment ]
  2. Liver function test [ Time Frame: daily from first dose of study treatment to the 7th day ]
  3. serum Paracetamol levels (blood analysis) after a single dose of study drug and after final dose of study drug. [ Time Frame: baseline, 30, 45, 90, 240 minutes after single dose. 240 minutes after final dose of study drug ]
  4. Temperature (bladder and tympanic) [ Time Frame: Hourly from first study drug treatment until 4 hours after final study drug treatment ]
    Time-weighted mean, area under the 3-day temperature curve, daily maximum and minimum temperature

  5. The use of physical cooling interventions [ Time Frame: hourly during the period of study intervention ]
  6. Intracranial pressure [ Time Frame: 6 hourly during the period of study intervention ]
    Mean daily intracranial pressure for day 1, 2 and 3.

  7. Incidence of cerebral hypoperfusion [ Time Frame: During study intervention period ]
    1. Systolic blood pressure < 90 mmhg or Mean arterial pressure < 50 mmhg for > 15 minutes
    2. Cerebral perfusion pressure < 50 mmhg for > 15 minutes



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Written informed consent has been obtained from the patient's next of kin
  • Age > 18 and < 65
  • Non penetrating head injury requiring mechanical ventilation, and, with an abnormal CT head (defined by the presence of haemorrhage, contusion, swelling, compression of basal cisterns or herniation)
  • Within 72 hours of injury
  • Presence (or imminent placement) of arterial cannula
  • Alanine transferase level < 100

Exclusion Criteria:

  • Suspected paracetamol overdose or allergy to paracetamol
  • Confirmed or suspected pregnancy
  • Use of pharmacological or physical intervention that reduces body temperature in the 6-hour period prior to randomisation.
  • Clinician decision to institute any pharmacological or physical intervention that modifies body temperature
  • Body temperature at time of recruitment less that 36°C or greater than 38.9°C
  • History of chronic liver disease or chronic alcohol abuse
  • Suspected malnutrition: BMI < 18 kg/m2 or weight < 60 kg
  • BMI > 35 kg/m2
  • Renal failure with serum creatinine > 200
  • Haemodynamic instability defined as systolic blood pressure < 90 mmhg or requirement for noradrenaline or adrenaline exceeding 20mcg/minute
  • Use of hepatic enzyme inducers, except for phenytoin
  • Minor head injury: either normal CT head or not expected to be in intensive care for 72 hours
  • GCS = 3 with fixed dilated pupils
  • Moribund patient expected to die within 24 hours

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231139


Locations
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Australia, New South Wales
St George Hospital
Sydney, New South Wales, Australia
Australia, Queensland
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia
Sponsors and Collaborators
Dr. M.K. Saxena
The George Institute
The University of New South Wales
Royal Brisbane and Women's Hospital
Investigators
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Principal Investigator: Manoj Saxena South East Sydney Illawarra Area Health Service

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Responsible Party: Dr. M.K. Saxena, Intensive Care Physician, South East Sydney and Illawarra Area Health Service
ClinicalTrials.gov Identifier: NCT01231139     History of Changes
Other Study ID Numbers: PARITY
First Posted: November 1, 2010    Key Record Dates
Last Update Posted: October 28, 2014
Last Verified: October 2014
Keywords provided by Dr. M.K. Saxena, South East Sydney and Illawarra Area Health Service:
Brain Injury
Temperature
Paracetamol
Phase 2
TBI
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics