Comparing triple therapy to double therapy for pulmonary arterial hypertension
Randomized Trial Comparing Efficacy and Safety of Initial Triple Therapy Including Parenteral Treprostinil to Initial Double Oral Therapy in Pulmonary Arterial Hypertension (PAH) Group I Patients (TripleTRE)
This study is testing if a new combination of three medications can help adults with severe pulmonary arterial hypertension feel better compared to the usual two-medication treatment.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 110 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | AOP Orphan Pharmaceuticals AG Industry-sponsored |
| Locations | 19 sites (Linz and 18 other locations) |
| Trial ID | NCT06317805 on ClinicalTrials.gov |
What this trial studies
This clinical trial, known as TripleTRE, investigates the effectiveness of an initial triple combination therapy that includes parenteral treprostinil alongside two oral medications, compared to a standard double oral therapy in patients with pulmonary arterial hypertension (PAH). The study focuses on treatment-naïve adults who are classified as intermediate-high risk or intermediate-low risk with severe hemodynamic impairment. Participants will be randomly assigned to one of the two treatment arms, and the primary endpoint will assess the proportion of patients achieving low-risk status after 24 to 48 weeks of treatment. The trial aims to optimize therapy concepts for PAH based on current European guidelines.
Who should consider this trial
Good fit: Ideal candidates for this study are treatment-naïve adults aged 18 to 70 with a confirmed diagnosis of pulmonary arterial hypertension and classified as intermediate-high risk or intermediate-low risk with severe hemodynamic impairment.
Not a fit: Patients who are not treatment-naïve or those with mild pulmonary arterial hypertension may not receive benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a more effective treatment option for patients with pulmonary arterial hypertension, potentially improving their risk status and overall health outcomes.
How similar studies have performed: Other studies have shown promise with similar combination therapies in pulmonary arterial hypertension, but this specific approach is being evaluated for the first time in this context.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Signed informed consent prior to any trial-mandated procedure * Male or female ≥ 18 and ≤ 70 years of age * Symptomatic treatment-naïve PAH patients (group I) with confirmed diagnosis of one of the following subgroups: * idiopathic pulmonary arterial hypertension (IPAH) * hereditary pulmonary arterial hypertension (HPAH) * Drug and toxin-induced pulmonary arterial hypertension (DPAH) * PAH associated with Connective Tissue Disease * PAH with corrected congenital heart disease 4. Intermediate-high risk patients rated acc. the simplified four-strata risk-assessment tool or intermediate-low risk with severe hemodynamic impairment as defined in current PH guidelines i.e., mean right atrial pressure (RAP) ≥ 20 mmHg, cardiac index (CI) \< 2.0 L/min, stroke volume index (SVI) \< 31 mL/m2 and/or pulmonary vascular resistance (PVR) ≥ 12 WU * Right Heart Catheterization (RHC) meeting all the following criteria: * Mean pulmonary arterial pressure (mPAP) \> 20 mmHg * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg * PVR \> 2 Wood Units * Women of childbearing potential must not be pregnant or lactating, must perform regular pregnancy tests, if sexually active, agrees to continue to use reliable method(s) of contraception until study completion Exclusion Criteria: * PAH patients (group I) belonging to one of the following subgroups: * Schistosomiasis * HIV infection * Portal hypertension * Diffuse systemic sclerosis * Uncorrected congenital heart disease including uncorrected systemic-to-pulmonary shunts * Any PAH-specific drug therapy in the past 3 months * Patients responding to vasoreactivity testing with calcium channel blockers (CCB) * Post-capillary PH and left heart disease * Known or suspected pulmonary veno-occlusive disease (PVOD) * Any PH due to lung disease * Any disorder of the respiratory system expressed by Diffusing Capacity of Lung for Carbon Monoxide (DLCO) \<40% and a noticeable imaging result (e.g., CT) and (Total Lung Capacity) TLC \<60% and (Forced Expiratory Volume) FEV1 \<70% by plethysmography (a pulmonary function test) * Patients with need of ambulatory or long-term oxygen therapy * Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) \> 480 msec at screening * Body mass index (BMI) \> 35 (kg/m2) * Age \> 70 years * History of restrictive, constrictive or congestive cardiomyopathy, atrial septostomy, any symptomatic coronary disease events within 6 months, severe uncontrolled arterial hypertension, acutely decompensated heart failure and myocardial infarction within 30 days, significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, chronic systemic hypotension, unstable angina pectoris, permanent/persistent atrial fibrillation and/or need for pacemaker * Patients with acute anemia with hemoglobin (Hb) values \<11g/dL * Cerebrovascular accident within 3 months * Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin \> 3× upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) \> ULN and/or Child-Pugh Class C * Documented renal insufficiency with Glomerular Filtration Rate (GFR) \<30 ml/min * Patients with untreated sleep apnea * Patient with other cardiovascular, liver, renal, hematologic, gastrointestinal (including active gastrointestinal ulcer), immunologic, endocrine (e.g., uncontrolled diabetes), metabolic, or central nervous system disease and acute bleeding and injuries (e.g., intracranial hemorrhage) that, in the opinion of the investigator, may adversely affect the safety of the patient and /or efficacy of the therapy or significantly limit the lifespan (\< 12 months) * Patients with major surgery in the last 12 months * Known history of alcohol abuse * Treatment of a a cytochrome P450 (CYP)2C8 enzyme inducer (e.g., rifampicin) ≤ 28 days and/or treatment of a CYP2C8 enzyme inhibitor (e.g., gemfibrozil) ≤ 28 days * Treatment with another investigational drug (planned, or taken ≤ 12 weeks) * Hypersensitivity to any of the trial treatments or any excipient of their formulations * Pregnancy, breastfeeding, or intention to become pregnant during the trial * Any other significant disease or disorder which, in the opinion of the investigator, may put the patients at risk when participating in the trial * Any factor or condition likely to affect protocol compliance of the patient, as judged by the investigator.
Where this trial is running
Linz and 18 other locations
- Ordensklinikum Linz — Linz, Austria (Recruiting)
- Medical University Vienna — Vienna, Austria (Recruiting)
- Fakultní Nemocnice Olomouc — Olomouc, Czechia (Not_yet_recruiting)
- Všeobecná fakultní nemocnice v Praze — Prague, Czechia (Not_yet_recruiting)
- Hôpital Bicêtre-- Assistance Publique Hopitaux de Paris — Paris, France (Not_yet_recruiting)
- Hôpitaux Universitaires de Strasbourg — Strasbourg, France (Not_yet_recruiting)
- DRK Kliniken Berlin Westend — Berlin, Germany (Not_yet_recruiting)
- University Hospital Carl Gustav Carus of Technical University Dresden — Dresden, Germany (Not_yet_recruiting)
- Universitätsmedizin Greifswald — Greifswald, Germany (Not_yet_recruiting)
- Gottsegen National Cardiovascular lnstitute — Budapest, Hungary (Not_yet_recruiting)
- Medical University of Szeged — Szeged, Hungary (Not_yet_recruiting)
- Sapienza University of Rome — Rome, Italy (Recruiting)
- John Paul II Hospital Krakow — Krakow, Poland (Not_yet_recruiting)
- Fryderyk Chopin Hospital in European Health Centre Otwock — Otwock, Poland (Not_yet_recruiting)
- Centro Hospitalar Lisboa Norte - Santa Maria University Hospital — Lisbon, Portugal (Not_yet_recruiting)
- Emergency Institute for Cardiovascular Diseases Prof. Dr. C.C.Iliescu — Bucharest, Romania (Not_yet_recruiting)
- Emergency Clinical County Hospital of Targu Mures — Târgu Mureş, Romania (Not_yet_recruiting)
- Hospital Clinic of Barcelona — Barcelona, Spain (Not_yet_recruiting)
- Hospital Ramon y Cajal — Madrid, Spain (Not_yet_recruiting)
Study contacts
- Study coordinator: Clinical Project Manager
- Email: tripletre@aoporphan.com
- Phone: +43676 3464650
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.