Riociguat for treatment of PAH in children from 6 to less than 18 years old

• Conditions: Hypertension, Pulmonary; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2014-003952-29-IT
• Lead Sponsor: Bayer Healthcare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-15
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Children aged =6 to <18 years
2. Diagnosed with PAH :
- Idiopathic (IPAH)
- Hereditable (HPAH)
- PAH associated with (APAH)
o Connective tissue disease
o Congenital heart disease with shunt closure more than 6 months ago (no open shunts, confirmed by RHC no less than 4 months after surgery)
3. Diagnosis of PAH confirmed by right heart catheterization (RHC) at any time prior to enrolment (for patients with closed shunts – RHC no less than 4 months after surgery)
4. Pulmonary arterial hypertension confirmed by a RHC at any time prior to start of study, with mean pulmonary artery pressure (PAPmean) =25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) =15 mmHg, and pulmonary vascular resistance (PVR) >240 dyn•sec•cm-5 (i.e., =3.0 wood units•m2)
5. Patients must be treated with standard of care comprising background therapy and stable
dose of bosentan (at least 12 weeks with stable doses).
Two groups of patients will be included:
o Prevalent: Patients currently on monotherapy with bosentan who need additional treatment (discretion of the investigator)
o Incident: Treatment naïve patients initiated on bosentan then riociguat added once bosentan dose is stable for at least 12 weeks.
5. WHO functional class I-III
6. Adolescent females of childbearing potential can only be included in the study if a
pregnancy test is negative. Adolescent females of childbearing potential must agree to use
adequate contraception when sexually active. ‘Adequate contraception’ is defined as any
combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Adequate contraception is required from the signing of the informed consent form up until 6 weeks after the last study drug administration.
7. Young men must agree to use adequate contraception when sexually active.
8. Written inform consent provided and if applicable child assent provided
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Concomitant use of the following medication: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific PDE inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form, or pre-treatment within the last 2-weeks before Visit 1: NO donors (e.g. nitrates)
2. Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening
3. Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004)
4. History of left-sided heart disease, including valvular disease or heart failure
5. Pulmonary hypertension related to conditions other than specified in the inclusion criteria
6. WHO functional class IV
7. Pulmonary veno-occlusive disease
8. Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN)
9. Non-stable disease status, e.g. , signs and symptoms of decompensated right heart failure
10. Severe bronchial asthma
11. Severe restrictive lung disease
12. Severe congenital abnormalities of the lung, thorax, and diaphragm
13. Clinically relevant hepatic dysfunction (especially Child Pugh C)
14. Renal insufficiency (glomerular filtration rate <30 mL/min e.g. calculated based on Cockroft formula)
15. Subject with hypersensitivity to the investigational drug or any of the excipients
16. Active smoking of tobacco of any type or quantity
17. Subjects with known HIV infection (evaluated by medical history)
18. Previous assignment to treatment during this study
19. Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s)
20. Any condition that, according to treating physician, might jeopardize subject's participation and compliance with procedures indicated in this protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified