ESRA
Research type
Research Study
Full title
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
IRAS ID
1005672
Contact name
Ekkehard Grünig
Contact email
Sponsor organisation
Thoraxklinik-Heidelberg gGmbH
Eudract number
2021-001633-40
Clinicaltrials.gov Identifier
Research summary
Chronic pulmonary arterial hypertension (PAH) is associated with impaired exercise capacity, quality of life (QoL) and right ventricular function. The disease is characterized by an increase of pulmonary vascular resistance (PVR) and pulmonary arterial pressure, leading to right heart insufficiency. Riociguat is a soluble guanylate cyclase stimulator and the first drug that has been approved for the treatment of both PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Early diagnosis of systemic sclerosis associated PAH (SSc-APAH) is of utmost importance, since it leads to significant improvement of survival rates through the implementation of PAH-targeted therapies. In order to enhance early diagnosis of patients with pulmonary vascular disease, a new hemodynamic definition of PAH was proposed at the 6th World Symposium of PH, which lowers the cut-off values of diagnostic parameters. The change in the hemodynamic definition of pre-capillary PH represents a step towards the upper limit of physiological hemodynamic thresholds. The new PAH definition will most likely prevent an early PAH-diagnosis. Since PVR may be an indicator of early pulmonary vascular disease and has a prognostic significance among patients with SSc-APAH, it was chosen as primary endpoint in the study. The aim of this study is to investigate the effect of riociguat (MK-4836) on PVR, clinical parameters, safety and tolerability in patients with early pulmonary vascular disease.
The study will include 70 patients in Germany, Austria, Switzerland, Italy, France and UK and is anticipated to end in 2027. The participants will undergo the following examinations: Vital signs, Right Heart Cathetherisation (RHC), Electrocardiogram (ECG), Echocardiography, Blood gas analysis (BGA), Diffusion capacity of the lung (DL), 6-minute walking distance (6MWD), Plethysmography and blood tests, especially N-terminal pro brain natriuretic peptide (NT-proBNP).REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
23/EM/0065
Date of REC Opinion
20 Sep 2023
REC opinion
Further Information Favourable Opinion