OBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk
of febrile seizure recurrence include young age at onset, family history
of febrile seizures, previous recurrent febrile seizures, time lapse since
previous seizure <6 months, relative low temperature at the initial
seizure, multiple type initial seizure, and frequent febrile illnesses.
Prevention of seizure recurrences serves two useful purposes: meeting
parental fear of recurrent febrile seizures in general and reducing the
(small) risk of a long-lasting and eventually injurious recurrent seizure.
In daily practice, children with febrile seizures often are treated with
antipyretics during fever to prevent febrile seizure recurrences. Thus
far, no randomized placebo-controlled trial has been performed to assess
the efficacy of intermittent antipyretic treatment in the prevention of
seizure recurrence. METHODS: We performed a randomized, double-blind,
placebo-controlled trial. Children 1 to 4 years of age who had had at
least one risk factor for febrile seizure recurrence were enrolled. They
were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5
mg) per kilogram of body weight per dose, or matching placebo, to be
administered every 6 hours during fever (temperature, >/=38.5 degrees C).
Parents were instructed to take the child's rectal temperature immediately
when the child seemed ill or feverish and to promptly administer the study
medication when the temperature was >/=38.5 degrees C. Doses were to be
administered every 6 hours until the child was afebrile for 24 hours. The
parents were instructed not to administer any other antipyretic drug to
the child. For measuring rectal temperature, a Philips HP5316 digital
thermometer (Philips, Eindhoven, The Netherlands) was distributed. During
subsequent treatment of the fever episode, parents had to call the
investigator at least once each day to notify the investigator in case of
febrile seizure recurrence. The investigator could be contacted by parents
24 hours per day. The primary outcome was the first recurrence of a
febrile seizure. Kaplan-Meier curves and Cox regression were used for the
statistical analysis. The treatment effect on the course of the
temperature was assessed using analysis of covariance, with temperature at
fever onset as covariate. Two analyses were performed. In an
intention-to-treat analysis, all first recurrences were considered
regardless of study medication compliance. A per-protocol analysis was
limited to those recurrences that occurred in the context of study
medication compliance. RESULTS: Between October 1, 1994, and April 1,
1996, 230 children were randomly assigned to ibuprofen syrup (111
children) or placebo (119 children). Median follow-up time was 1.04 years
(25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98
years (0.7-1.6 years) in the placebo group. Of all children, 67 had a
first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in
the placebo group. The 2-year recurrence probabilities were 32% and 39%,
