A double-blind clinical trial on diphenhydramine in pertussis.

Patients were prospectively included in the study if they were younger than 12 months of age, if nurses noted characteristic whooping spells, and if the cases were not treated with steroids. Randomization and allocation of treatment followed a double-blind pattern, according to a list determined by the ParkeDavis Company from a table of random numbers. The hospital pharmacy was responsible for the assignment of patients to the treatment groups. The following baseline data were measured: age at entry, previous vaccination for pertussis, interval between the first paroxysm and hospitalization, concomitant administration of erythromycin, and presence of an opacity on chest radiography. Since patients were included in the trial at different stages of their disease, the number of fits during the 24 hours preceding the introduction of drug or placebo was measured as an indicator of the severity of disease at time zero. Systematic laboratory tests included white blood cell count, lymphocyte count, glycemia, chest radiography, viral serology, and three nasopharyngeal cultures for B. pertussis. Paired serum specimen, obtained at least two-weeks apart, were tested for complement fixing antibody to adenovirus, influenza, parainfluenza and respiratory syncitial virus. Appearance, smell, and taste of active and placebo syrups were similar. Patients in the experimental group received 5 mg/kg/day of the active drug in three doses. The outcome was the frequency of paroxysms between the 25th and the 48th hour after initiation of treatment. Monitoring was similar for all patients. Coughs were monitored around the clock with a system of microphones set up in each room. All patients were fed with frequent small meals. None received sedatives or humidity. The average number of fits per day was compared with a Student's t-test. A dummy regression analysis was used to test the hypothesis that the slopes for the compared groups were parallel (no interaction between prognostic factors and treatment). Having accepted that the slopes were parallel, the mean number of fits per day was compared in the two groups, adjusting for baseline data and the number of fits during the 24 hours preceding entry into the trial. Results were considered as significant for p<0.05. The smallest detectable difference between the two groups, given the sample size, was estimated using a formula suggested by Lachin (1). Informed consent was obtained from a parent or a guardian for each patient. The study was approved by the Ethics Committee of Sainte-Justine Hospital.