Traumatic Brain InjuryPhase 2PARITYNCT01231139
The Paracetamol AfteR Traumatic Brain InjurY Study
A Phase 2 study testing Paracetamol and 0.9% Sodium Chloride Schedule: in people with Traumatic Brain Injury, run by Dr. M.K. Saxena at 2 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Paracetamol and 0.9% Sodium Chloride Schedule:
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 2 sitesAustralia
- Study dates
- Oct 2010to Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Royal Brisbane and Women's Hospital
Brisbane, Queensland
St George Hospital
Sydney, New South Wales
About this study
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
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.
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Paracetamol, 0.9% Sodium Chloride Schedule:
- Keywords
- Brain Injury, Temperature, Paracetamol, Phase 2, TBI
- Medical subject headings
- Brain Injuries, Traumatic, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
Also called Perfalgan
Intravenous paracetamol, 1 gram (100mls), administered over 30 minutes (every 4 hours for 3 days).
0.9% Sodium Chloride Schedule:Drug
Also called Saline
Identical placebo: 100mls saline given intravenous over 30 minutes (every 4 hours for 3 days)
| Study group | Role | What they receive |
|---|---|---|
| Paracetamol | Experimental | Paracetamol dissolved in 0.9% Sodium Chloride Receives: Drug: Paracetamol |
| 0.9% Sodium Chloride | Placebo comparator | 0.9% Sodium Chloride Receives: Drug: 0.9% Sodium Chloride Schedule: |
What is being measured
The primary outcome is the main question the study is designed to answer.
Core body temperature: bladder temperature probe
Measured: 30 minutes after final dose of study drug has been administered
Secondary outcomes (7)
Blood Pressure (systolic and mean arterial pressure) measured by intra-arterial pressure monitor
Measured: 6 hourly during study treatment
Liver function test
Measured: daily from first dose of study treatment to the 7th day
serum Paracetamol levels (blood analysis) after a single dose of study drug and after final dose of study drug.
Measured: baseline, 30, 45, 90, 240 minutes after single dose. 240 minutes after final dose of study drug
Temperature (bladder and tympanic)
Time-weighted mean, area under the 3-day temperature curve, daily maximum and minimum temperature
Measured: Hourly from first study drug treatment until 4 hours after final study drug treatment
The use of physical cooling interventions
Measured: hourly during the period of study intervention
Intracranial pressure
Mean daily intracranial pressure for day 1, 2 and 3.
Measured: 6 hourly during the period of study intervention
Incidence of cerebral hypoperfusion
- Systolic blood pressure < 90 mmhg or Mean arterial pressure < 50 mmhg for > 15 minutes
- Cerebral perfusion pressure < 50 mmhg for > 15 minutes
Measured: During study intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionDec 2013
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. M.K. Saxena
- Sponsor type
- University, hospital or other
- Collaborators
- The George Institute, The University of New South Wales, Royal Brisbane and Women's Hospital
- Responsible party
- Sponsor-investigator, Dr. M.K. Saxena, South East Sydney and Illawarra Area Health Service
- Investigators
- Manoj Saxena, Principal investigator, South East Sydney Illawarra Area Health Service
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231139
- Sponsor's protocol ID
- PARITY
- Acronym
- PARITY
- Status last verified
- Oct 2014
- First submitted
- 29 Oct 2010
- Last updated
- 28 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01231139
- Acronym / sponsor ID
- PARITY / PARITY
- Conditions
- Traumatic Brain Injury
- Keywords
- Brain Injury, Temperature, Paracetamol, Phase 2, TBI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Dr. M.K. SaxenaUniversity, hospital or other
- Collaborators
- The George Institute, The University of New South Wales, Royal Brisbane and Women's Hospital
- Study start
- Oct 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 1 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paracetamol | Experimental | Drug: ParacetamolParacetamol dissolved in 0.9% Sodium Chloride |
| 0.9% Sodium Chloride | Placebo comparator | Drug: 0.9% Sodium Chloride Schedule:0.9% Sodium Chloride |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParacetamolAlso: PerfalganIntravenous paracetamol, 1 gram (100mls), administered over 30 minutes (every 4 hours for 3 days). | Drug | Paracetamol |
| 0.9% Sodium Chloride Schedule:Also: SalineIdentical placebo: 100mls saline given intravenous over 30 minutes (every 4 hours for 3 days) | Drug | 0.9% Sodium Chloride |
Primary outcome
Core body temperature: bladder temperature probe
Time frame: 30 minutes after final dose of study drug has been administered
7 secondary outcomes
Blood Pressure (systolic and mean arterial pressure) measured by intra-arterial pressure monitor
Time frame: 6 hourly during study treatment
Liver function test
Time frame: daily from first dose of study treatment to the 7th day
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
Temperature (bladder and tympanic)
Time frame: Hourly from first study drug treatment until 4 hours after final study drug treatment
The use of physical cooling interventions
Time frame: hourly during the period of study intervention
Intracranial pressure
Time frame: 6 hourly during the period of study intervention
Incidence of cerebral hypoperfusion
Time frame: During study intervention period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2014.
Related trials for Traumatic Brain Injury
Enrolling by invitationObservational study
Assessment of Traumatic Brain Injury Using Transcranial Magnetic Stimulated Evoked Potentials
Traumatic Brain Injury
RecruitingObservational study
CoMind Early Feasibility Study
Intracranial Pressure, Intracranial Pressure Changes
Enrolling by invitation
Improving In-hospital and Post-discharge Patient Education for Mild Traumatic Brain Injury
Concussion, Mild, Traumatic Brain Injury
Not yet recruitingObservational study
Description of Clinicians' Predictive Abilities Before and After a Diffusion Tensor Imaging (DTI)
Diffusion Tensor Imaging Prognosis, Brain Injury, Traumatic
Enrolling by invitation
Risk Assessment of Mild Traumatic Brain Injury in Military Training
Trauma, Brain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manoj Saxena principal investigator
South East Sydney Illawarra Area Health Service
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paracetamol and 0.9% Sodium Chloride Schedule: in people with Traumatic Brain Injury, run by Dr. M.K. Saxena at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core body temperature: bladder temperature probe (time frame: 30 minutes after final dose of study drug has been administered). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2014.