The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: a phase II double-blind randomised placebo-controlled trial

ISRCTN	ISRCTN98608690
DOI	https://doi.org/10.1186/ISRCTN98608690
Secondary identifying numbers	N/A

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Dr Diederik WJ Dippel
Scientific

Dept of Neurology
University Hospital Rotterdam
PO Box 2040
Rotterdam
3000 CR
Netherlands

Phone	+31 (0)10 4639222
Email	dippel@neuro.fgg.eur.nl

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title
Study acronym	PISA
Study objectives	To study the effect of high-dose ibuprofen and to confirm the previously observed reducing effect of high-dose paracetamol on body temperature, and to study their safety in normothermic and subfebrile patients with acute ischaemic stroke.
Ethics approval(s)	The medical ethics committees of the three hospitals have approved this protocol.
Health condition(s) or problem(s) studied	Stroke
Intervention	1. Paracetamol 6 g daily, for 5 days 2. Ibuprofen 2.4 g daily, for 5 days 3. Placebo for 5 days
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Paracetamol (acetaminophen), ibuprofen
Primary outcome measure	Body temperature at 24 hours from start of treatment.
Secondary outcome measures	1. Change in baseline temperature at 1 and 5 days from start of treatment 2. Time with elevated body temperature (greater than 37.0°C) (area under the curve) during the first 24 hours and the first five days Tertiary outcomes: Functional outcome at one month, as determined by the scores on the modified Rankin Scale (mRS) and Barthel Index (BI).
Overall study start date	01/12/2000
Completion date	31/12/2001

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target number of participants	75
Key inclusion criteria	1. An acute ischaemic anterior circulation stroke 2. A body temperature greater than 36.0°C or less than 39.0°C 3. A CT scan that is compatible with acute ischaemic stroke 4. A focal deficit without rapid improvement 5. A possibility to start treatment within 24 hours after stroke onset
Key exclusion criteria	1. Severe aphasia, defined as an aphasia score of 2 or 3 on the National Institutes of Health Stroke Scale (NIHSS) 2. Treatment with an non-Steroidal Anti-Inflammatory Drug (NSAID) deemed necessary 3. Hypersensitivity to ibuprofen or paracetamol 4. (Chronic) liver failure or cirrhosis 5. (Chronic) renal failure 6. History of alcohol abuse 7. Active gastric ulcer disease or a history of peptic ulceration or gastro-intestinal haemorrhage in the preceding year 8. Colitis ulcerosa 9. Pregnancy 10. Use of corticosteroids 11. A severe concomitant medical condition that could affect the assessment of the effect of the study medication on temperature 12. Residual neurological impairment resulting from a previous stroke that may hamper the assessment of functional outcome 13. Death appearing imminent 14. No informed consent given
Date of first enrolment	01/12/2000
Date of final enrolment	31/12/2001

Dept of Neurology

Rotterdam
3000 CR
Netherlands

Erasmus Medical Center (The Netherlands)
Hospital/treatment centre

P.O. Box 1738
Rotterdam
3000 DR
Netherlands

Website	http://www.erasmusmc.nl/content/englishindex.htm
"ROR"	https://ror.org/018906e22

Research organisation

Rotterdam Neurovascular Research Foundation (Stichting Neurovasculair Onderzoek Rotterdam) (The Netherlands)

No information available

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	Protocol	27/03/2002		Yes	No
Results article	Results	06/02/2003		Yes	No