Primary objective: To assess the effect of early treatment with paracetamol in a daily dose of 6 g for three consecutive days in patients with acute stroke and a body temperature of 36.5°C or above on the occurrence of a favorable functional outcome…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the score on the modified Rankin Scale (mRS).
Secondary outcome
The secondary outcomes will be poor outcome defined as mRS>2 at 3 months; score
on the Barthel index and EQ5D score at 3 months; and body temperature 24 hours
after start of treatment.
Background summary
In patients with acute stroke, increased body temperature is related to poor
functional outcome. In the Copenhagen study, the risk of poor outcome doubled
with every degree Celsius increase in body temperature. Animal studies have
suggested that a rise in temperature results in increased ischemic damage
through increased cerebral metabolic demands, increased blood-brain barrier
permeability, acidosis, and an increased release of excitatory amino acids. In
the Paracetamol (Acetaminophen) in Stroke (PAIS) trial, a double blind,
placebo-controlled randomized clinical trial of 1400 patients with acute
stroke, more paracetamol-treated patients than placebo-treated patients showed
improvement on the modified Rankin scale (mRS), yet the difference was not
statistically significant (adjusted Odds Ratio (aOR) 1.21; 95% Confidence
Interval (CI): 0.97-1.51). In the 661 patients with a baseline body temperature
of 36.5°C or above, paracetamol yielded a larger decrease in temperature than
in those with a baseline temperature lower than 36.5°C, and increased the odds
of improvement (aOR, 1.31; 95% CI: 1.01-1.68).
Study objective
Primary objective:
To assess the effect of early treatment with paracetamol in a daily dose of 6 g
for three consecutive days in patients with acute stroke and a body temperature
of 36.5°C or above on the occurrence of a favorable functional outcome.
Secondary objectives:
1. To investigate the association between body temperature in the first 12-36
hours after acute stroke and serum inflammation markers.
2. To investigate the relationship between paracetamol in a daily dose of 6 g
for three days and an inflammatory response in stroke.
Study design
PAIS 2 is a multicenter, randomized, double-blind placebo-controlled clinical
trial.
Intervention
About fifty percent of the patients receive 6 gram paracetamol a day for 3
days, the rest receive placebo.
Study burden and risks
In two pilot trials, and in the PAIS trial, paracetamol in a dose of 6 g/day
was neither associated with hepatotoxicity nor with other side effects. In the
PAIS trial the number of serious adverse events was similar in both treatment
groups. Paracetamol has only a small effect on body temperature. Yet, when
treatment will be proven effective, a simple, safe and inexpensive therapy will
be available for many patients with acute stroke.
Dr. Molewaterplein 50
Rotterdam 3015 GE
NL
Dr. Molewaterplein 50
Rotterdam 3015 GE
NL
Listed location countries
Age
Inclusion criteria
- clinical diagnosis of ischemic stroke or intracerebral hemorrhage, confirmed by CT or MRI scan within 24 hours after inclusion in the study
- a measurable deficit on the National Institutes of Health Stroke Scale (NIHSS)
- the possibility to start treatment within 12 hours of symptom onset (for patients who noticed symptoms when awaking from sleep, the time last seen well is taken as the time of onset of symptoms)
- a body temperature of 36.5°C or higher
- age of 18 years or older
- signed informed consent
Exclusion criteria
- a history of liver disease or alcohol abuse
- liver enzymes (ASAT, ALAT, AP or gamma-GT) increased above twice the upper limit of normal values
- allergy to paracetamol
- death appearing imminent at the time of inclusion
- any pre-stroke impairment that has led to dependency (modified Rankin scale (mRS)>2) and therefore interferes with the assessment of functional outcome.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-021437-30-NL |
| CCMO | NL32932.078.10 |