A practical approach to the evaluation of antihypertensive agents in infants and children: Study design and outcome measures

Background: The causes of hypertension, especially in infants and young chi ldren, are largely secondary to systemic diseases, and primary hypertension is uncommon in this population. Objective: The aim of this article was to discuss some of the problems invo lved in designing appropriate antihypertensive trials for children and to s uggest the essential features of a well-designed trial in the pediatric pop ulation. Methods: A review of pediatric studies was conducted to define the features of childhood hypertension. Results: This review showed that numerous therapeutic approaches have been used, making many of the identified studies difficult to interpret. Conclusions: The design of studies of antihypertensive medications in child ren requires a novel approach. The method of measuring blood pressure is pi votal; 24-hour ambulatory blood pressure monitoring is the optimal method. Because children with secondary hypertension may be symptomatic, a washout period before the onset of a trial's drug phase will permit the investigato r to use the patient as his or her own control. Whether children should be exposed to a second period of hypertension and symptoms in a randomized was hout period at the end of several weeks of therapy is controversial. Study end points include blood pressure measurements (systolic and diastolic) ver sus appropriate percentiles, an attenuation of the dip in nocturnal blood p ressure, and the concept of blood pressure load (the percentage of time wit h elevated blood pressure values). Safe and effective guidelines can be des igned for therapeutic trials of pediatric hypertension. The result will be enhancement of the therapeutic choices available for children with hyperten sion.