Randomizowane badanie porównujące skuteczność i bezpieczeństwo stosowania leczenia wstępnego trzema lekami, w tym treprostynilem podawanym pozajelitowo, z leczeniem wstępnym dwoma lekami podawanymi doustnie u pacjentów z TNP należących do grupy I – TripleTRE

Kryteria wyłączenia kto nie może wziąć udziału (26)

1. 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
2. Any PAH-specific drug therapy in the past 3 months
3. Patients responding to vasoreactivity testing with calcium channel blockers (CCB)
4. Post-capillary PH and left heart disease
5. Known or suspected pulmonary veno-occlusive disease (PVOD)
6. Any PH due to lung disease
7. Any disorder of the respiratory system expressed by DLCO <40% and a noticeable imaging result (e.g., CT) and TLC <60% and FEV1 <70% by plethysmography (a pulmonary function test)
8. Patients with need of ambulatory or long-term oxygen therapy
9. Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 480 msec at randomization
10. Body mass index (BMI) > 35 (kg/m2)
11. Age > 70 years
12. 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
13. Patients with acute anaemia with haemoglobin (Hb) values <11 g/dL
14. Cerebrovascular accident within 3 months
15. 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
16. Documented renal insufficiency with GFR <30 ml/min
17. Patients with untreated sleep apnoea
18. Patient with other cardiovascular, liver, renal, haematologic, 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 haemorrhage) 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)
19. Patients with major surgery in the last 12 months
20. Known history of alcohol abuse
21. Treatment of a CYP2C8 enzyme inducer (e.g., rifampicin) ≤ 28 days and/or treatment of a cytochrome P450 (CYP)2C8 enzyme inhibitor (e.g., gemfibrozil) ≤ 28 days
22. Treatment with another investigational drug (planned, or taken ≤ 12 weeks)
23. Hypersensitivity to any of the trial treatments or any excipient of their formulations
24. Pregnancy, breastfeeding, or intention to become pregnant during the trial
25. Any other significant disease or disorder which, in the opinion of the investigator, may put the patients at risk when participating in the trial
26. Any factor or condition likely to affect protocol compliance of the patient, as judged by the investigator