NCT05339087

Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH

Efficacy and Safety of Riociguat (MK-4836) in Incipient Pulmonary Vascular Disease as an Indicator for Early Pulmonary Arterial Hypertension Double-blind, Randomized, Multicenter, Multinational, Placebo-controlled Phase IIa Study (ESRA)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (actual)
• Sponsor: Heidelberg University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, double-blind, placebo-controlled, multicenter, multinational study investigating the effect of riociguat (MK-4836) in patients with early pulmonary vascular disease.

Detailed description

Chronic pulmonary arterial hypertension (PAH) is associated with impaired exercise capacity, quality of life and right ventricular function characterized by an increase of pulmonary vascular resistance (PVR) and pulmonary arterial pressure, leading to right heart insufficiency. Riociguat tratment is approved for both PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Data on early treatment of patients with mildly elevated pulmonary arterial pressures is still scarce but there is evindence that such patients may benefit from early targeted therapy. For instance, in a trial on systemic sclerosis (SSc)-patients with mildly elevated mean pulmonary artery pressure (mPAP) and/or exercise pulmonary hypertension, without significant left heart or lung disease, ambrisentan, an endothelin receptor antagonist resulted in an improvement of PVR as secondary endpoint, which may be of prognostic relevance in this patient cohort and requires further research. Besides its prognostic significance among patients with SSc-APAH, PVR may be an indicator of early pulmonary vascular disease and previous studies proved the positive effects of riociguat on right heart size and PVR (secondary endpoint in phase III studies). Thus, PVR was chosen as primary endpoint of this study aiming to investigate the effect of riociguat (MK-4836) on PVR, clinical parameters, safety and tolerability in patients with early pulmonary vascular disease. Eligible subjects will be randomized in a 1:1 ratio to receive either riociguat or placebo. Medical examinations include medical history, physical examination, electrocardiogram, blood gas analyses, lung function tests, laboratory testing (including NT-proBNP), echocardiography at rest, and right heart catheterization. The prospective period of data collection comprises a 24-week treatment phase diveded into an 8-week titration phase followed by a 16-week main study phase as well as a safety follow-up of 30±14 days.

Conditions

• Pulmonary Vascular Disorder
• Primary Pulmonary Hypertension
• Systemic Sclerosis
• Other Systemic Involvement of Connective Tissue

Interventions

Type	Name	Description
DRUG	Riociguat Oral Tablet	Riociguat Oral Tablet (1 mg, 1.5 mg, 2.0 mg or 2.5 mg three times daily) Titration phase: dose will be individually adjusted in accordance with the in-label titration regimen. Dose adjustment will be performed every two weeks by phone taking the systemic blood pressure of the patient, the subjects and physicians' subjective estimation and occurrence of adverse reactions into account. At week 8 the maintenance dose will be established and continued for the rest of the study
OTHER	Placebo	Sham titration and adjustment to maintenance dose will be performed according to individual tolerability as in the experimental arm.

Timeline

• Start date: 2022-10-24
• Primary completion: 2025-07-31
• Completion: 2025-07-31
• First posted: 2022-04-21
• Last updated: 2026-01-21
• Results posted: 2026-01-21

Locations

8 sites across 6 countries: Austria, France, Germany, Italy, Switzerland, United Kingdom