PMID- 20430262
OWN - NLM
STAT- MEDLINE
DCOM- 20100513
LR  - 20220330
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 55
IP  - 18
DP  - 2010 May 4
TI  - Addition of inhaled treprostinil to oral therapy for pulmonary arterial 
      hypertension: a randomized controlled clinical trial.
PG  - 1915-22
LID - 10.1016/j.jacc.2010.01.027 [doi]
AB  - OBJECTIVES: This study assessed the efficacy and safety of inhaled treprostinil 
      in pulmonary arterial hypertension (PAH) patients receiving therapy with either 
      bosentan or sildenafil. BACKGROUND: There is no cure for PAH, despite effective 
      treatments, and outcomes remain suboptimal. The addition of inhaled treprostinil, 
      a long-acting prostacyclin analog, might be a safe and effective treatment 
      addition to other PAH-specific oral therapies. METHODS: Two hundred thirty-five 
      PAH patients with New York Heart Association (NYHA) functional class III (98%) or 
      IV symptoms and a 6-min walk distance (6MWD) of 200 to 450 m while treated with 
      bosentan (70%) or sildenafil were randomized to inhaled treprostinil (up to 54 
      mug) or inhaled placebo 4 times daily. The primary end point was peak 6MWD at 12 
      weeks. Secondary end points included time to clinical worsening, Borg Dyspnea 
      Score, NYHA functional class, 12-week trough 6MWD, 6-week peak 6MWD, quality of 
      life, and PAH signs and symptoms. The biomarker N-terminal pro-brain natriuretic 
      peptide (NT-proBNP) was assessed. RESULTS: Twenty-three patients withdrew from 
      the study prematurely (13 treprostinil, 10 placebo). The Hodges-Lehmann 
      between-treatment median difference in change from baseline in peak 6MWD was 19 m 
      at week 6 (p = 0.0001) and 20 m at week 12 (p = 0.0004). Hodges-Lehmann 
      between-treatment median difference in change from baseline in trough 6MWD at 
      week 12 was 14 m (p = 0.0066). Quality of life measures and NT-proBNP improved on 
      active therapy. There were no improvements in other secondary end points, 
      including time to clinical worsening, Borg Dyspnea Score, NYHA functional class, 
      and PAH signs and symptoms. Inhaled treprostinil was safe and well-tolerated. 
      CONCLUSIONS: This trial demonstrates that, among PAH patients who remain 
      symptomatic on bosentan or sildenafil, inhaled treprostinil improves exercise 
      capacity and quality of life and is safe and well-tolerated. (TRIUMPH I: Double 
      Blind Placebo Controlled Clinical Investigation Into the Efficacy and 
      Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary 
      Arterial Hypertension; NCT00147199).
CI  - Copyright 2010 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - McLaughlin, Vallerie V
AU  - McLaughlin VV
AD  - University of Michigan Health System, CVC Cardiovascular Medicine, Ann Arbor, 
      Michigan 48109-5853, USA. vmclaugh@umich.edu
FAU - Benza, Raymond L
AU  - Benza RL
FAU - Rubin, Lewis J
AU  - Rubin LJ
FAU - Channick, Richard N
AU  - Channick RN
FAU - Voswinckel, Robert
AU  - Voswinckel R
FAU - Tapson, Victor F
AU  - Tapson VF
FAU - Robbins, Ivan M
AU  - Robbins IM
FAU - Olschewski, Horst
AU  - Olschewski H
FAU - Rubenfire, Melvyn
AU  - Rubenfire M
FAU - Seeger, Werner
AU  - Seeger W
LA  - eng
SI  - ClinicalTrials.gov/NCT00147199
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfonamides)
RN  - 0 (Sulfones)
RN  - 0 (Vasodilator Agents)
RN  - 0 (pro-brain natriuretic peptide (1-76))
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - Q326023R30 (Bosentan)
RN  - RUM6K67ESG (treprostinil)
SB  - IM
CIN - Nat Rev Cardiol. 2010 Jul;7(7):359. PMID: 21080575
MH  - Administration, Inhalation
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antihypertensive Agents/*administration & dosage
MH  - Bosentan
MH  - Drug Therapy, Combination
MH  - Epoprostenol/administration & dosage/*analogs & derivatives
MH  - Exercise Tolerance/drug effects
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Peptide Fragments/blood
MH  - Piperazines/*administration & dosage
MH  - Purines/administration & dosage
MH  - Quality of Life
MH  - Sildenafil Citrate
MH  - Sulfonamides/*administration & dosage
MH  - Sulfones/*administration & dosage
MH  - Treatment Outcome
MH  - Vasodilator Agents/*administration & dosage
MH  - Young Adult
EDAT- 2010/05/01 06:00
MHDA- 2010/05/14 06:00
CRDT- 2010/05/01 06:00
PHST- 2009/07/21 00:00 [received]
PHST- 2009/12/17 00:00 [revised]
PHST- 2010/01/04 00:00 [accepted]
PHST- 2010/05/01 06:00 [entrez]
PHST- 2010/05/01 06:00 [pubmed]
PHST- 2010/05/14 06:00 [medline]
AID - S0735-1097(10)00779-5 [pii]
AID - 10.1016/j.jacc.2010.01.027 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2010 May 4;55(18):1915-22. doi: 10.1016/j.jacc.2010.01.027.