protocolSection identificationModule nctId: NCT06317805, orgStudyIdInfo id: TREV1-10P.401, secondaryIdInfos id: 2023-504351-26-01, type: CTIS, briefTitle: Initial Triple Therapy Including Parenteral Treprostinil vs Initial Double Oral Therapy in PAH Group I Patients, acronym: TripleTRE, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-12-06, primaryCompletionDateStruct date: 2027-06, completionDateStruct date: 2027-06-30, studyFirstPostDateStruct date: 2024-03-19, lastUpdatePostDateStruct date: 2024-03-19, sponsorCollaboratorsModule leadSponsor name: AOP Orphan Pharmaceuticals AG, class: INDUSTRY, collaborators name: ANOVA CRO s.r.o., collaborators name: PharmaLex Belgium, collaborators name: Aixial s.r.o., collaborators name: GCP-Service International Ltd. & Co. KG, descriptionModule briefSummary: TripleTRE investigates the effect of initial triple combination therapy (oral endothelin receptor antagonist (ERA) + oral phosphodiesterase tyüe-5 inhibitor (PDE-5i) + parenteral treprostinil) compared to double oral therapy (oral ERA + oral PDE-5i) in pulmonary arterial hypertension (PAH) patients (group I) with intermediate-high risk or patients with intermediate-low risk with severe hemodynamic impairment at baseline in a prospective, randomized, unblinded setting with scope of increasing evidence for optimization of therapy concepts in PAH.The effect of initial triple combination therapy vs initial double oral therapy (standard of care (SoC)) will be measured by primary endpoint: (non)response to the assigned treatment., conditionsModule conditions: Pulmonary Arterial Hypertension, designModule studyType: INTERVENTIONAL, phases: PHASE4, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Prospective, randomized, two-arm, open-label, low-interventional, phase IV, multi-centre clinical trial comparing efficacy and safety of initial triple therapy including parenteral treprostinil to initial double oral therapy (background therapy with endothelin receptor antagonist - ERA and phosphodiesterase type-5 inhibitor - PDE-5i) by proportion of patients achieving low risk status according to the simplified four-strata risk-assessment tool from week 24 up to 48 weeks in 110 (55/group) treatment-naïve adult intermediate-high risk or intermediate-low risk patients with severe hemodynamic impairment with pulmonary arterial hypertension (PAH) (group I)., primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 110, type: ESTIMATED, armsInterventionsModule interventions name: Generic treprostinil sodium + Standard of Care (Double Oral), interventions name: Standard of Care - Double Oral, outcomesModule primaryOutcomes measure: Patients achieving (non-)response status to the assigned treatment in terms of achievement of low-risk status, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - PVR, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - mPAP, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - mRAP, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - CI, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - CO, secondaryOutcomes measure: Change in hemodynamic parameters by means of right heart catheterization (RHC) - RAP, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - TAPSE/sPAP, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - RVEDA, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - RVESA, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - RVFAC, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - RA, secondaryOutcomes measure: Change in right heart structure and function assessed by echocardiography - Pericardial effusion, secondaryOutcomes measure: Time to achievement of low-risk status, secondaryOutcomes measure: Rate of change of risk status, secondaryOutcomes measure: Change in the number of low-risk criteria based on the French PH Network Registry (FPHR) risk assessment tool, secondaryOutcomes measure: Change in REVEAL 2.0 risk score, secondaryOutcomes measure: Rate of change in WHO-FC, secondaryOutcomes measure: Rate of change in 6MWD, secondaryOutcomes measure: Rate of change in NT-proBNP/BNP levels, secondaryOutcomes measure: Total number of clinical worsening(s), secondaryOutcomes measure: Overall and transplant free survival, secondaryOutcomes measure: Rate of change in quality of life - emPHasis-10, secondaryOutcomes measure: Rate of change in quality of life - EQ-5D-5L, otherOutcomes measure: Safety outcomes:, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 70 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Ordensklinikum Linz, status: RECRUITING, city: Linz, country: Austria, contacts name: Regina Steringer-Mascherbauer, role: CONTACT, phone: +437327676, phoneExt: 4916, email: regina.steringer-mascherbauer@ordensklinikum.at, contacts name: Regina Steringer-Mascherbauer, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.30639, lon: 14.28611, locations facility: Medical University Vienna, status: RECRUITING, city: Vienna, country: Austria, contacts name: Irene Lang, role: CONTACT, phone: +43140400, phoneExt: 4623, email: irene.lang@meduniwien.ac.at, contacts name: Irene Lang, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.20849, lon: 16.37208, locations facility: Fakultní Nemocnice Olomouc, status: NOT_YET_RECRUITING, city: Olomouc, country: Czechia, contacts name: Jan Přeček, role: CONTACT, phone: +420588445102, email: jan.precek@fnol.cz, contacts name: Jan Přeček, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 49.59552, lon: 17.25175, locations facility: Všeobecná fakultní nemocnice v Praze, status: NOT_YET_RECRUITING, city: Praha, country: Czechia, contacts name: Pavel Jansa, role: CONTACT, phone: +420224962629, email: pavel.jansa@vfn.cz, contacts name: Pavel Jansa, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.08804, lon: 14.42076, locations facility: Hôpital Bicêtre-- Assistance Publique Hopitaux de Paris, status: NOT_YET_RECRUITING, city: Paris, country: France, contacts name: Olivier Sitbon, role: CONTACT, phone: +33145217883, email: olivier.sitbon@abc.aphp.fr, contacts name: Olivier Sitbon, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Hôpitaux Universitaires de Strasbourg, status: NOT_YET_RECRUITING, city: Strasbourg, country: France, contacts name: Marianne Riou, role: CONTACT, phone: +330369550686, email: marianne.riou@chru-strasbourg.fr, contacts name: Marianne Riou, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 48.58392, lon: 7.74553, locations facility: DRK Kliniken Berlin Westend, status: NOT_YET_RECRUITING, city: Berlin, country: Germany, contacts name: Christian Opitz, role: CONTACT, phone: +493030354815, email: c.opitz@drk-kliniken-berlin.de, contacts name: Christian Opitz, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 52.52437, lon: 13.41053, locations facility: University Hospital Carl Gustav Carus of Technical University Dresden, status: NOT_YET_RECRUITING, city: Dresden, country: Germany, contacts name: Michael Halank, role: CONTACT, phone: +4935145813981, email: michael.halank@uniklinikum-dresden.de, contacts name: Michael Halank, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 51.05089, lon: 13.73832, locations facility: Universitätsmedizin Greifswald, status: NOT_YET_RECRUITING, city: Greifswald, country: Germany, contacts name: Ralf Ewert, role: CONTACT, phone: +4938348680500, email: ewert@uni-greifswald.de, contacts name: Ralf Ewert, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 54.09311, lon: 13.38786, locations facility: Gottsegen National Cardiovascular lnstitute, status: NOT_YET_RECRUITING, city: Budapest, country: Hungary, contacts name: Olga Hajnalka Balint, role: CONTACT, phone: +3612152139, email: titkarsag@kardio.hu, contacts name: Olga Hajnalka Balint, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 47.49801, lon: 19.03991, locations facility: Medical University of Szeged, status: NOT_YET_RECRUITING, city: Szeged, country: Hungary, contacts name: Gergely Ágoston, role: CONTACT, phone: +3662545553, email: agoston.gergely@med.u-szeged.hu, contacts name: Gergely Ágoston, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 46.253, lon: 20.14824, locations facility: Sapienza University of Rome, status: RECRUITING, city: Rome, country: Italy, contacts name: Roberto Badagliacca, role: CONTACT, phone: +39064402727, email: roberto.badagliacca@uniroma1.it, contacts name: Roberto Badagliacca, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.89193, lon: 12.51133, locations facility: John Paul II Hospital Krakow, status: NOT_YET_RECRUITING, city: Kraków, country: Poland, contacts name: Grzegorz Kopeć, role: CONTACT, phone: +48126143399, contacts name: Grzegorz Kopeć, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 50.06143, lon: 19.93658, locations facility: Fryderyk Chopin Hospital in European Health Centre Otwock, status: NOT_YET_RECRUITING, city: Otwock, country: Poland, contacts name: Marcin Kurzyna, role: CONTACT, phone: +48227103052, email: marcin.kurzyna@ecz-otwock.pl, contacts name: Marcin Kurzyna, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 52.10577, lon: 21.26129, locations facility: Centro Hospitalar Lisboa Norte - Santa Maria University Hospital, status: NOT_YET_RECRUITING, city: Lisboa, country: Portugal, contacts name: Rui Miguel Freire Plácido, role: CONTACT, phone: +351217805306, email: rui.placido@chln.min-saude.pt, contacts name: Rui Miguel Freire Plácido, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 38.71667, lon: -9.13333, locations facility: Emergency Institute for Cardiovascular Diseases Prof. Dr. C.C.Iliescu, status: NOT_YET_RECRUITING, city: Bucharest, country: Romania, contacts name: Ioan Mircea Coman, role: CONTACT, phone: +40213175222, contacts name: Ioan Mircea Coman, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.43225, lon: 26.10626, locations facility: Emergency Clinical County Hospital of Targu Mures, status: NOT_YET_RECRUITING, city: Târgu-Mureş, country: Romania, contacts name: Ioan Tilea, role: CONTACT, phone: +40265215551, email: ioan.tilea@umfst.ro, contacts name: Ioan Tilea, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 46.54245, lon: 24.55747, locations facility: Hospital Clinic of Barcelona, status: NOT_YET_RECRUITING, city: Barcelona, country: Spain, contacts name: Isabel Blanco Vich, role: CONTACT, phone: +34932275779, email: iblanco2@clinic.cat, contacts name: Isabel Blanco Vich, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.38879, lon: 2.15899, locations facility: Hospital Ramon y Cajal, status: NOT_YET_RECRUITING, city: Madrid, country: Spain, contacts name: Jose Andres Tenes Mayen, role: CONTACT, phone: +34913368263, email: jtenes@salud.madrid.org, contacts name: Jose Andres Tenes Mayen, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 40.4165, lon: -3.70256, hasResults: False