title: A randomized, open-label, dose-response study of losartan in hypertensive children.
abstract: OBJECTIVE
  Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6-16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years.
  
  
  METHODS
  This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout.
  
  
  RESULTS
  Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups.
  
  
  CONCLUSIONS
  Hypertensive children aged 6 months to 6 years treated with losartan 0.1-0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated.
authors.affiliation: Department of Paediatric Nephrology and National Institute for Health Research/Wellcome Trust Children's Clinical Research Facility, University of Manchester, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Manchester, United Kingdom; nicholas.webb@cmft.nhs.uk.
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
authors.affiliation: Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas;
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wells
authors.affiliation: S. Shahinfar Consulting Inc., Newtown Square, Pennsylvania; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Shahinfar
authors.affiliation: MSD Europe Inc., Brussels, Belgium;
authors.forename: Rachid
authors.initials: R
authors.lastname: Massaad
authors.affiliation: Parexel International, Durham, North Carolina; and.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Dankner
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Chun
authors.initials: C
authors.lastname: Lam
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Emanuela Palumbo
authors.initials: EP
authors.lastname: Santoro
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Christine
authors.initials: C
authors.lastname: McCrary Sisk
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Blaustein
mesh_terms: D000367:Age Factors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007223:Infant; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D019808:Losartan
keywords: children; clinical trial; hypertension; pediatrics