Efficacy and safety of valsartan in children aged 1–5 years with hypertension, with or without chronic kidney disease: a randomized, double-blind study followed by open-label phase

Abstract

Objective To assess the dose–response relationship for reduction in mean systolic blood pressure (MSBP) with valsartan solution, in young children with hypertension with or without chronic kidney disease (CKD). Methods In this multicenter, randomized, double-blind, double-dummy study, 127 young children aged 1–5 years with hypertension (MSBP ≥95th percentile) were randomized (1:1) to receive valsartan 0.25 or 4 mg/kg/day for 6 weeks, followed by a 20 week open-label phase, where patients received valsartan 1 mg/kg/day for 4 weeks, and then optionally titrated to 2 mg/kg/day or up to 4 mg/kg/day. The primary endpoint was the change in MSBP from baseline at Week 6 during the double-blind phase. Results Overall, 120 patients (94.5%) completed the study; 63 had CKD. A clinically and statistically significant reduction in MSBP from baseline to Week 6 was observed with the valsartan 4 mg/kg group compared with the valsartan 0.25 mg/kg group (8.5 vs 4.1 mmHg; p = .0157). A positive dose–response relationship for MSBP reduction was observed between the 0.25 mg/kg and 4 mg/kg groups (p = .0012). In the CKD subgroup, a significant reduction in MSBP was observed with 4 mg/kg (9.2 mmHg) versus 0.25 mg/kg (1.2 mmHg; p = .0096). In the non-CKD subgroup, a numerically greater decrease in MSBP was observed with 4 mg/kg (7.8 mmHg) versus 0.25 mg/kg (6.9 mmHg; p = .6531). Incidence of adverse events was lower with valsartan 4 mg/kg than 0.25 mg/kg (41.9% vs 51.6%) and similar between CKD and non-CKD subgroups (48.4% vs 45.3%) irrespective of dose. Increase in serum potassium (>20% compared to baseline) was observed more frequently in patients with CKD compared to non-CKD patients. Conclusion Valsartan was efficacious and well tolerated in children 1 to 5 years of age with hypertension, with or without CKD. Clinical trial registration: The study has been registered at ClinicalTrials.gov (Identifier: NCT01617681).