PMID- 28228114
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20181113
IS  - 1471-2466 (Electronic)
IS  - 1471-2466 (Linking)
VI  - 17
IP  - 1
DP  - 2017 Feb 23
TI  - Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with 
      pulmonary arterial hypertension: a randomized, double-blind study with open-label 
      extension.
PG  - 44
LID - 10.1186/s12890-017-0374-x [doi]
LID - 44
AB  - BACKGROUND: In a previous study, 6-minute walk distance (6MWD) improvement with 
      sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 
      times daily [TID]). This study assessed whether lower doses were less effective 
      than the approved 20-mg TID dosage. METHODS: Treatment-naive patients with 
      pulmonary arterial hypertension were randomized to 12 weeks of double-blind 
      sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID 
      followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 
      or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, 
      functional class, and biomarkers were assessed. RESULTS: The study was 
      prematurely terminated for non-safety reasons, with 129 of 219 planned patients 
      treated. At week 12, 6MWD change from baseline was significantly greater for 
      sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At week 24, 6MWD 
      increases from baseline were larger in those initially randomized to 20 versus 5 
      or 1 mg (74 vs 50 and 47 m, respectively). At week 12, changes in hemodynamic 
      parameters were generally small and variable between treatment groups; odds 
      ratios for improvement in functional class were not statistically significantly 
      different. Improvements in B-type natriuretic peptide levels were significantly 
      greater with sildenafil 20 versus 1 but not 5 mg. CONCLUSIONS: Sildenafil 20 mg 
      TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 
      5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID. 
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00430716 (Registration date: January 
      31, 2007).
FAU - Vizza, Carmine Dario
AU  - Vizza CD
AUID- ORCID: 0000-0002-3540-4983
AD  - Department of Cardiovascular and Respiratory Disease, University of Rome La 
      Sapienza, Viale del Policlinico 155, 00161, Rome, Italy. dario.vizza@gmail.com.
FAU - Sastry, B K S
AU  - Sastry BK
AD  - CARE Hospitals, Gandhi Bhavan Road Nampally, Hyderabad, India.
FAU - Safdar, Zeenat
AU  - Safdar Z
AD  - Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
FAU - Harnisch, Lutz
AU  - Harnisch L
AD  - Pfizer Ltd, Ramsgate Road, Sandwich Kent, CT13 9NJ, UK.
FAU - Gao, Xiang
AU  - Gao X
AD  - Pfizer Inc, 558 Eastern Point Rd, Groton, CT, 06340, USA.
FAU - Zhang, Min
AU  - Zhang M
AD  - Pfizer Inc, 10646 Science Center Dr, La Jolla Campus, San Diego, CA, 92121, USA.
FAU - Lamba, Manisha
AU  - Lamba M
AD  - Pfizer Inc, 558 Eastern Point Rd, Groton, CT, 06340, USA.
FAU - Jing, Zhi-Cheng
AU  - Jing ZC
AD  - Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507, Zhengmin 
      Road, Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT00430716
SI  - ClinicalTrials.gov/NCT00430716
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170223
PL  - England
TA  - BMC Pulm Med
JT  - BMC pulmonary medicine
JID - 100968563
RN  - 0 (Vasodilator Agents)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Echocardiography
MH  - Female
MH  - *Hemodynamics
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy
MH  - International Cooperation
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Severity of Illness Index
MH  - Sildenafil Citrate/administration & dosage/*therapeutic use
MH  - Treatment Outcome
MH  - Vasodilator Agents/administration & dosage/*therapeutic use
MH  - Walk Test
MH  - Young Adult
PMC - PMC5322647
OTO - NOTNLM
OT  - Clinical trial
OT  - Dose
OT  - Echocardiography
OT  - Exercise test
OT  - Pulmonary hypertension
OT  - Sildenafil
EDAT- 2017/02/24 06:00
MHDA- 2017/11/03 06:00
PMCR- 2017/02/23
CRDT- 2017/02/24 06:00
PHST- 2016/05/13 00:00 [received]
PHST- 2017/01/31 00:00 [accepted]
PHST- 2017/02/24 06:00 [entrez]
PHST- 2017/02/24 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2017/02/23 00:00 [pmc-release]
AID - 10.1186/s12890-017-0374-x [pii]
AID - 374 [pii]
AID - 10.1186/s12890-017-0374-x [doi]
PST - epublish
SO  - BMC Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.