The Paracetamol AfteR Traumatic Brain InjurY Study (PARITY)

This study has been completed.
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
ClinicalTrials.gov Identifier:
NCT01231139
First received: October 29, 2010
Last updated: October 26, 2014
Last verified: October 2014

October 29, 2010
October 26, 2014
October 2010
December 2013   (final data collection date for primary outcome measure)
Core body temperature: bladder temperature probe [ Time Frame: 30 minutes after final dose of study drug has been administered ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01231139 on ClinicalTrials.gov Archive Site
  • Blood Pressure (systolic and mean arterial pressure) measured by intra-arterial pressure monitor [ Time Frame: 6 hourly during study treatment ] [ Designated as safety issue: Yes ]
  • Liver function test [ Time Frame: daily from first dose of study treatment to the 7th day ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Temperature (bladder and tympanic) [ Time Frame: Hourly from first study drug treatment until 4 hours after final study drug treatment ] [ Designated as safety issue: No ]
    Time-weighted mean, area under the 3-day temperature curve, daily maximum and minimum temperature
  • The use of physical cooling interventions [ Time Frame: hourly during the period of study intervention ] [ Designated as safety issue: No ]
  • Intracranial pressure [ Time Frame: 6 hourly during the period of study intervention ] [ Designated as safety issue: No ]
    Mean daily intracranial pressure for day 1, 2 and 3.
  • Incidence of cerebral hypoperfusion [ Time Frame: During study intervention period ] [ Designated as safety issue: Yes ]
    1. Systolic blood pressure < 90 mmhg or Mean arterial pressure < 50 mmhg for > 15 minutes
    2. Cerebral perfusion pressure < 50 mmhg for > 15 minutes
  • Blood Pressure (systolic and mean arterial pressure) measured by intra-arterial pressure monitor [ Time Frame: 6 hourly during study treatment ] [ Designated as safety issue: Yes ]
  • Liver function test [ Time Frame: daily from first dose of study treatment to the 7th day ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Temperature (bladder and tympannic) [ Time Frame: Hourly from first study drug treatment until 4 hours after final study drug treatment ] [ Designated as safety issue: No ]
    Time-weighted mean, area under the 3-day temperature curve, daily maximum and minimum temperature
  • The use of physical cooling interventions [ Time Frame: hourly during the period of study intervention ] [ Designated as safety issue: No ]
  • Intracranial pressure [ Time Frame: 6 hourly during the period of study intervention ] [ Designated as safety issue: No ]
    Mean daily intracranial pressure for day 1, 2 and 3.
  • Incidence of cerebral hypoperfusion [ Time Frame: During study intervention period ] [ Designated as safety issue: Yes ]
    1. Systolic blood pressure < 90 mmhg or Mean arterial pressure < 50 mmhg for > 15 minutes
    2. Cerebral perfusion pressure < 50 mmhg for > 15 minutes
Not Provided
Not Provided
 
The Paracetamol AfteR Traumatic Brain InjurY Study
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
  • Drug: Paracetamol
    Intravenous paracetamol, 1 gram (100mls), administered over 30 minutes (every 4 hours for 3 days).
    Other Name: Perfalgan
  • Drug: 0.9% Sodium Chloride Schedule:
    Identical placebo: 100mls saline given intravenous over 30 minutes (every 4 hours for 3 days)
    Other Name: Saline
  • Experimental: Paracetamol
    Paracetamol dissolved in 0.9% Sodium Chloride
    Intervention: Drug: Paracetamol
  • Placebo Comparator: 0.9% Sodium Chloride
    0.9% Sodium Chloride
    Intervention: Drug: 0.9% Sodium Chloride Schedule:
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
June 2014
December 2013   (final data collection date for primary outcome measure)
  • 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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT01231139
PARITY
Yes
Dr. M.K. Saxena, South East Sydney and Illawarra Area Health Service
Dr. M.K. Saxena
  • The George Institute
  • The University of New South Wales
  • Royal Brisbane and Women's Hospital
Principal Investigator: Manoj Saxena South East Sydney Illawarra Area Health Service
South East Sydney and Illawarra Area Health Service
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP