A double-blind, dose-response study of losartan in hypertensive children

Background: The aim of this study was to determine the dose-response relationship for losartan, 2.5 to 100 mg, and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age. Methods: This was a multicenter, randomized, doubleblind, dose-response study. In Period 1, a total of 175 patients were stratified by weight (<50 kg and greater than or equal to50 kg) and randomized to one of three dose groups by stratum (low, 2.5/5.0 mg; middle, 25/50 mg; or high, 501100 mg) for 3 weeks. The ratio of the three dose levels for both weight strata was 1:10:20. In Period 2, patients in each dose group were randomized to continue the same treatment or placebo washout for 2 additional weeks. Results: In Period 1, sitting trough diastolic blood pressure (DBP) decreased in a dose-dependent manner (P <.0001). At week 3, changes in DBP from baseline in the low-, middle-, and high-dose groups were -6.0 mm Hg, - 11.7 mm Hg, and - 12.2 mm Hg, respectively. In Period 2, DBP increased significantly in patients who switched from middle- and high-dose losartan to placebo (mean increase 6.0 turn Hg, P =.003) relative to DBP in patients who remained on active treatment; however, these levels remained stable in those patients who switched from lowdose losartan to placebo (mean increase 1.1 mm Hg, P.628). Conclusions: In hypertensive children 6 to 16 years of age, losartan given once daily reduced blood pressure in a dose-dependent fashion. A once-daily starting dose of losartan, 0.75 mg/kg (maximum 50 mg) effectively lowered DBP within 3 weeks. Losartan up to a dosage of 1.44 mg/kg (maximum 100 mg) once daily is generally well tolerated. Am J Hypertens 2005;18:183-190 (C) 2005 American Journal of Hypertension, Ltd.