6533b838fe1ef96bd12a5055
RESEARCH PRODUCT
Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension:A Double-Blind Placebo-controlled Clinical Trial
R. James WhiteCarlos Jerjes-sanchezGisela Martina Bohns MeyerTomas PulidoPablo SepulvedaKuo Yang WangEkkehard GrünigShirish HiremathZaixin YuZhang GangchengWei Luen James YipShuyang ZhangAkram KhanC. Q. DengRob GroverVictor F. TapsonGraciela Noemi SvetlizaAdrian Jose LescanoGuillermo Roberto BortmanFabian Antonio DiezChristian Edgardo BottaJohn FitzgeraldEelke FeenstraFiona Dawn KermeenAnne Margaret KeoghTrevor John WilliamsPeter Paul YousseffBenjamin Joh-han NgDavid Mcnaughton SmallwoodNathan Brent DwyerMartin Russell BrownIrene M LangRegina Steringer-mascherbauerJaquelina Sonoe Ota ArakakiFrederico Thadeu Assis Figueiredo CamposRicardo De Amorim CorreaRogerio De SouzaGisela M. Bohns MeyerMaria Auxiliadora Carmo MoreiraHugo Hyung Bok YooMonica Silveira LapaJohn SwistonNaushad HiraniSanjay MehtaEvangelos MichelakisPablo Andres SepulvedaMonica Maria Zagolin BlancaireJimming LiuZhang ShuyangLei PanBao ChundeYi QunCheng XiaoshuYu ZaixinXinli LiYao HuaZhang GangchengXianyang ZhuYundai ChenCheng ZhaozhongYuanhua YangZhou DaxinShen JieyanJens Erik Nielsen-kudskJorn CarlsenArnaud BourdinEric HachullaClaire DromerAri ChaouatMartine Reynaud-gauberMarie-france SerondeHans KloseMichael HalankGert HoffkenRalf EwertStephan RosenkranzEkkehard GrunigUlrich KrugerJuliane KronsbeinBarbara Monika HauptmeierAndrea KochMatthias HeldTobias Johannes LangeClaus NeurohrHeinrike WilkensHubert Rolf Wilhelm WirtzStavros KonstantinidesParaskevi Argyropoulou-patakaStylianos OrfanosShirish HiremathPrafulla Gopinath KerkarPujar Venkateshacharya SureshHemang Ashwinkumar BaxiAbraham OommanRajpal Kanaklal AbhaichandPadma Kumar Edla ArjunVijay ChopraRahul MehrotraRajeev Kumar RajputJitendra Pal Singh SawhneySubir BimalenduKamal Harishchandra SharmaBhagavathula Kutumba Srinivasa SastryMordechai Reuben KramerMichael Jonathan SegelIssahar Ben-dovNeville BerkmanMordechai YiglaYochai AdirMichael D’altoCarmine Dario VizzaLaura ScelsiPatrizio VituloTomas Rene PulidoCarlos Jerjes-sanchezAnko BoonstraMadelon Clementina VonkBozena SobkowiczTatiana Mularek-kubzdelaAdam TorbickiPiotr PodolecLim Soo TeikWei Luen James YipHyuk-jae ChangHyung-kwan KimJun-bean ParkSung-a ChangDuk-kyung KimSung-a ChangWook-jin ChungJong-min SongMagnus NissellClara HjalmarssonBengt RundqvistWei-chun HuangChin-chang ChengChih-hsin HsuHsao-hsun HsuKuo-yang WangJohn Gerard CoghlanDavid Gerard KielyJoanna Wanda Pepke-zabaJames Lawrence LordanPaul Anthony CorrisLinda CadaretSif HansdottirRonald Jack OudizDavid B. BadeschMichael MathierRobert SchilzNicholas HillAaron WaxmanCatherine J. MarkinDiane Lynn ZwickeMicah FisherVeronica FrancoNamita SoodMyung H. ParkRoblee AllenJeremy P. FeldmanVijay BalasubramanianVandana Kavita SeeramAbubakr BajwaAustin B. ThompsonChristina MiglioreJean ElwingJohn W. McconnellJinesh P. MehtaFranck Farzad RahaghiJ. Eduardo RameAkram KhanBela PatelRon M. OrenJames R. KlingerHassan AlnuaimatSamuel AllenWilliam HarveyMichael S. EggertAntoine HageChad E. MillerRana Lee Adawi AwdishHector CajigasDaniel GrinnanBenjamin Howard TrichonClark McdonoughR. James WhiteFranz Rischardsubject
MaleAdministration OralOral treprostinilCritical Care and Intensive Care MedicinePulmonary arterial hypertension[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tractcombination therapyoralepoprostenol0302 clinical medicinepulmonary arterial hypertensionmiddle agedClinical endpointdouble-blind methodMESH: Double-Blind MethodFamilial Primary Pulmonary Hypertension030212 general & internal medicinehumansMESH: AgedMESH: Middle AgedEpoprostenol/analogs & derivativesadultHazard ratioMiddle Aged[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciencesantihypertensive agents3. Good healthagedfemaleMESH: Young Adultoral treprostinilMESH: Administration Oralyoung adultFemalePulmonary Arterial Hypertension/drug therapymedicine.drugAdultPulmonary and Respiratory MedicineMESH: Pulmonary Arterial Hypertensionmedicine.medical_specialtyRandomizationAdolescentclinical study; combination therapy; oral treprostinil; pulmonary arterial hypertension; sequential therapy; administration oral; adolescent; adult; aged; antihypertensive agents; double-blind method; epoprostenol; female; humans; male; middle aged; placebos; pulmonary arterial hypertension; young adultSequential therapyMESH: PlacebosMESH: EpoprostenolLower riskPlaceboadministrationClinical studyYoung Adult03 medical and health sciencesDouble-Blind Method[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular systemmaleInternal medicineplacebosmedicineHumansCombination therapyAdverse effectPlacebos/therapeutic useAgedMESH: AdolescentPulmonary Vascular DiseaseMESH: Antihypertensive AgentsMESH: Humanssequential therapybusiness.industryMESH: AdultOriginal Articlesclinical studyMESH: MaleClinical trial030228 respiratory systemadolescentAntihypertensive Agents/administration & dosagebusinessMESH: FemaleTreprostinildescription
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-15 |