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)
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.
• 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