Evaluation of the dose-response relationship of amlodipine and losartan combination in patients with essential hypertension: an 8-week, randomized, double-blind, factorial, phase II, multicenter study

Am J Cardiovasc Drugs. 2012 Feb 1;12(1):35-47. doi: 10.2165/11597170-000000000-00000.

Abstract

Background: Despite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients.

Objective: The aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension.

Methods: This was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18-75 years with essential hypertension. At screening, patients received placebo for 2-4 weeks. Eligible patients (n=320) were randomized to one of eight treatment groups: amlodipine 5 mg or 10 mg, losartan 50 mg or 100 mg, amlodipine camsylate/losartan 5 mg/50 mg, 5 mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg.

Main outcome measures: The assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events.

Results: The reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100 mg versus amlodipine 10 mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant.

Conclusion: Combination amlodipine camsylate/losartan (5 mg/50 mg, 5 mg/100 mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension.

Clinical trial registration: Registered at clinicaltrials.gov: NCT00942344.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amlodipine / administration & dosage*
  • Antihypertensive Agents / administration & dosage*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Losartan / administration & dosage*
  • Male
  • Middle Aged

Substances

  • Antihypertensive Agents
  • Drug Combinations
  • Amlodipine
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00942344