A clinical trial to study the effects of selexipag on the heart in patients with Pulmonary Arterial Hypertensio

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 80

Inclusion Criteria

1.Signed informed consent prior to any study-mandated procedure
2.WHO FC II or III
3.PAH etiology belonging to one of the following groups according to classification:
• Idiopathic PAH
• Heritable PAH
• PAH associated with connective tissue disease
• PAH associated with congenital heart disease, with simple systemic-to-pulmonary shunt at least 1 year after surgical repair
4.First hemodynamic diagnosis of PAH by right heart catheterization (RHC) within 12 months prior to initiation of selexipag, showing:
• mPAP =25 mmHg and
• PA wedge pressure (PAWP) or LV end-diastolic pressure =15 mmHg and
• PVR >3 WU (240 dyn.s.cm-5)
5.For participants already receiving PAH-specific therapy, the PAH treatment dose must have been stable for at least 3 months before informed consent form (ICF) signature, and until Day 1
6.NT-proBNP >300 ng/mL at screening
7.Men or women =18 and <65 years
8.Women of childbearing potential (Section 10.5) must meet the following criteria:
• Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, and
• Agree to use reliable methods of contraception from Day 1 up to 30 days after study intervention discontinuation (Section 10.5), and
• If only using hormonal contraception, have used it for at least 1 month (30 days) before Day 1, and
• Agree to perform monthly pregnancy tests up to 30 days after study intervention discontinuation
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Prior use of IP-receptor agonist, prostacyclin, or prostacyclin analog. Use of such treatments for vasoreactivity testing is not exclusionary; intermittent use of such treatments for digital ulcers or Raynaud’s phenomenon is not exclusionary if stopped >6 months (180 days) prior to Day 1
2.Treatment with strong inhibitors of CYP2C8 (eg, gemfibrozil) within 28 days prior to Day 1
3.Treatment with another investigational drug planned or taken within 12 weeks (84 days) prior to Day 1
4.Cardiopulmonary rehabilitation programs based on exercise between informed consent and expected Week 26 visit date
5.Decompensated cardiac failure requiring hospitalization, emergency room visit or intravenous diuretics in the 6 weeks before informed consent
6.Severe coronary heart disease or unstable angina
7.Cerebrovascular events (eg, transient ischemic attack, stroke) within 3 months prior to Day 1
8.Left atrial volume indexed for body surface area =43 mL/m2, assessed by Echo or cardiac MRI
9.Myocardial infarction within 6 months prior to Day 1
10.Body mass index >40 kg/m2
11.Presence of one or more of the following signs of relevant lung disease at any time up to screening - if pulmonary function test results are missing, then exclusion 11 is considered as met
• Diffusing capacity of the lung for carbon monoxide <40% of predicted UNLESS computed tomography reveals no or mild interstitial lung disease
• Forced vital capacity <60% of predicted
• Forced expiratory volume in 1 second <60% of predicted
12.Known or suspected pulmonary veno-occlusive disease (PVOD)
13.Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension
14.SBP <90 mmHg at screening or on Day 1
15.Severe renal impairment (estimated creatinine clearance =30 mL/min/1.73 m2 or serum creatinine >2.5 mg/dL at screening) or ongoing or planned dialysis
16.Documented moderate or severe hepatic impairment (with or without cirrhosis) at screening, defined as Child-Pugh Class B or C
17.Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism)
18.Any hospitalization within 6 weeks prior to informed consent (except elective hospitalizations for surgery or standard monitoring of pre-existing conditions that did not worsen)
19.Concomitant life-threatening disease with a life expectancy of less than 12 months
20.Hemoglobin <80 g/L at screening
21.Hypersensitivity to selexipag or any study intervention excipient (mannitol, maize starch, hydroxypropylcellulose, magnesium stearate, hypromellose, propylene glycol, titanium dioxide, carnauba wax, iron oxide red, iron oxide yellow, iron oxide black)
22.Breastfeeding
23.Any factor or condition likely to affect compliance with study intervention or visit plan, as judged by the investigator
24.Claustrophobia
25.MRI-incompatible permanent cardiac pacemaker, automatic internal cardioverter
26.Metallic implant (eg, defibrillator, neurostimulator, hearing aid, permanent use of infusion device, dental brace, metal-containing tattoo ink)
27.Severe arrythmia, atrial fibrillation, multiple premature ventricular or atrial contractions, or any other condition that would interfere with proper cardiac gating during MRI

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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