PMID- 20110023
OWN - NLM
STAT- MEDLINE
DCOM- 20100402
LR  - 20121115
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 12
DP  - 2009 Dec
TI  - Evaluation of the dose--response relationship of aliskiren, a direct renin 
      inhibitor, in an 8-week, multicenter, randomized, double-blind, parallel-group, 
      placebo-controlled study in adult patients with stage 1 or 2 essential 
      hypertension.
PG  - 2839-50
LID - 10.1016/j.clinthera.2009.12.006 [doi]
AB  - BACKGROUND: Aliskiren is approved for the treatment of hypertension at once-daily 
      doses of 150 or 300 mg by the US Food and Drug Administration and the European 
      Commission. It is generally well tolerated and provides 24-hour, dose-dependent 
      blood pressure (BP) reduction; however, the effect of the 75-mg dose has been 
      inconsistent in previous trials. OBJECTIVES: This study was designed to assess 
      the efficacy and tolerability of once-daily administration of aliskiren 75 mg and 
      to evaluate the dose-response relationship across all 3 doses of aliskiren (75, 
      150, and 300 mg). METHODS: In this 8-week, multicenter, randomized, double-blind, 
      parallel-group, placebo-controlled study, patients aged > or =18 years with stage 
      1 or 2 essential hypertension entered a 3- to 4-week, single-blind, placebo 
      run-in period. Eligible patients were randomized (1:1:1:1) to receive oral, 
      once-daily doses of aliskiren 75, 150, or 300 mg or placebo. The primary efficacy 
      variable was the change from baseline in mean sitting diastolic BP (msDBP) at the 
      week-8 end point. Tolerability was assessed by monitoring and recording all 
      adverse events (AEs). RESULTS: A total of 642 patients (mean [SD] age, 52.0 
      [10.73] years; 60.0% male; 80.8% white; mean body weight, 89.2 [18.4] kg [range, 
      50-160 kg]) were included in the study. Overall, 576 patients (89.7%) completed 
      the double-blind treatment period. The most frequent reasons for discontinuation 
      were unsatisfactory therapeutic effect (27/642 randomized patients [4.2%]) and 
      AEs (17/642 [2.6%]). At end point, aliskiren 150 and 300 mg significantly reduced 
      msDBP (both, P < 0.001) and mean sitting systolic CONCLUSIONS: This study found a 
      positive linear dose-response relationship in BP reduction with aliskiren 75, 
      150, and 300 mg dosed once daily, but only aliskiren 150 and 300 mg provided 
      statistically significant reductions from baseline compared with placebo. All 3 
      doses of aliskiren were generally well tolerated.
CI  - Copyright 2009 Excerpta Medica Inc. All rights reserved.
FAU - Puig, Juan G
AU  - Puig JG
AD  - Vascular Risk Unit, Department of Internal Medicine, La Paz Hospital, Madrid, 
      Spain.
FAU - Schunkert, Heribert
AU  - Schunkert H
FAU - Taylor, Addison A
AU  - Taylor AA
FAU - Boye, Sam
AU  - Boye S
FAU - Jin, James
AU  - Jin J
FAU - Keefe, Deborah L
AU  - Keefe DL
LA  - eng
SI  - ClinicalTrials.gov/NCT00260923
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Amides)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Fumarates)
RN  - 502FWN4Q32 (aliskiren)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Amides/*administration & dosage/adverse effects
MH  - Antihypertensive Agents/*administration & dosage/adverse effects
MH  - Blood Pressure/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Europe
MH  - Female
MH  - Fumarates/*administration & dosage/adverse effects
MH  - Humans
MH  - Hypertension/*drug therapy/physiopathology
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Placebo Effect
MH  - Renin/*antagonists & inhibitors
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States
EDAT- 2010/01/30 06:00
MHDA- 2010/04/03 06:00
CRDT- 2010/01/30 06:00
PHST- 2009/09/30 00:00 [accepted]
PHST- 2010/01/30 06:00 [entrez]
PHST- 2010/01/30 06:00 [pubmed]
PHST- 2010/04/03 06:00 [medline]
AID - S0149-2918(09)00456-1 [pii]
AID - 10.1016/j.clinthera.2009.12.006 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Dec;31(12):2839-50. doi: 10.1016/j.clinthera.2009.12.006.