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Riociguat in Pediatric Pulmonary Arterial Hypertension: PATENT-CHILD Study Design and Rationale

Maurice Beghetti

G Wirsching

D Bonnet

Dunbar Ivy

shahin moledina

S Lippert

Sonia Ribeiro


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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1042

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.


The development of treatments for children with pulmonary arterial hypertension (PAH) remains challenging due to strict regulatory requirements and ethical issues.[1] Use of PAH-targeted therapies is based on results in adults and expert opinion, as well as limited trials in pediatric PAH.[2] These trials have shown that endothelin receptor antagonists (ERAs), prostacyclin analogs (PCAs), and phosphodiesterase type 5 (PDE5) inhibitors can improve hemodynamics and functional capacity.[2] Clinical trials of riociguat include the placebo-controlled PATENT-1 study,[3] its long-term extension PATENT-2,[4] and the open-label RESPITE study.[5] These trials have shown that riociguat is effective[3,4] and well tolerated[3–5] in adults with PAH, but it has not been investigated in children. PATENT-CHILD ( identifier: NCT02562235) will evaluate the safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of riociguat, added to standard of care, in pediatric patients with PAH.


PATENT-CHILD is an open-label, single-arm, individual dose-titration study in children and adolescents aged 6–17 years with PAH (diagnosed by right heart catheterization) in World Health Organization (WHO) functional class (FC) I–III. All patients must be on standard of care PAH-targeted therapies (ERA and/or PCA) for ≥12 weeks prior to the baseline visit, and will be classified as prevalent (receiving PAH medication at screening and in need of additional treatment) or incident (treatment naïve and stabilized on standard of care before addition of riociguat). Main exclusion criteria include concomitant PDE5 inhibitors, non-specific PDE inhibitors, nitrates, and nitric oxide (NO) donors, pre-treatment with NO donors within 2 weeks of Visit 1, active state of hemoptysis or pulmonary hemorrhage. The main study consists of a dose-adjustment phase up to 8 weeks and a maintenance phase up to 16 weeks (Figure). Eligible patients weighing <50 kg at screening will receive weight-adjusted doses of riociguat from 1 to 2.5 mg three times daily (TID) as granules for reconstitution into an oral pediatric suspension (0.15 mg/mL). Patients weighing ≥50 kg at screening will receive riociguat 1–2.5 mg TID as film-coated tablets. The primary outcome measures are change in safety and tolerability from baseline to Week 24 and PK/PD analyses. Safety and tolerability will be assessed by incidence of adverse events and serious adverse events, change in vital signs, left hand x-ray to monitor bone growth, and laboratory parameters. Exploratory efficacy endpoints comprise change from baseline to Week 24 in 6-minute walking distance, WHO FC, N-terminal pro-brain natriuretic peptide or brain natriuretic peptide, echocardiographic parameters, and time to clinical worsening. Questionnaires will be used to assess change in quality of life scores (SF-10 and PedsQL) and the taste and texture of the pediatric formulation. Patients who complete the initial 24-week study are eligible for entry into a long-term extension phase until they reach the age of 18 years or until riociguat is licensed commercially for pediatric treatment (a 60-day safety follow-up will be provided for patients who choose not to proceed).


The planned enrollment of at least 20 patients on ERA therapy is ongoing.


The PATENT-CHILD study will provide important new information about the potential use of riociguat in pediatric patients with PAH.

1. Beghetti M, Berger RM. Eur Respir Rev 2014;23:498–504;
2. Vorhies EE, Ivy DD. Paediatr Drugs 2014;16:43–65;
3. Ghofrani HA, et al. N Engl J Med 2013;369:330–340;
4. Ghofrani HA, et al. Lancet Respir Med 2016;4:361–371;
5. Hoeper MM, et al. Eur Respir J 2017;50:1602425.