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

Phase 2 Terminated 35 enrolled Heidelberg University Merck Sharp & Dohme LLC · collab

RandomizedParallel-groupDouble-blindTreatment

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.

Timeline

Start: 2022-10-24
Primary completion: 2025-07-31
Completion: 2025-07-31

Outcome

Met primary endpoint

Stopped (Business): “Strategic re-prioritization by the IMP supplier. Decision not safety-related.”

paper Riociguat significantly improved the primary end point of change in PVR PMID 42457022 ↗

registry analysis (superiority test); Riociguat vs Placebo; p = 0.043; ANCOVA NCT05339087 ↗

Publications

Background Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Rev Esp Cardiol (Engl Ed). 2016 Feb;69(2):177. doi: 10.1016/j.rec.2016.01.002. No abstract available.
Background Grunig E, Barner A, Bell M, Claussen M, Dandel M, Dumitrescu D, Gorenflo M, Holt S, Kovacs G, Ley S, Meyer JF, Pabst S, Riemekasten G, Saur J, Schwaiblmair M, Seck C, Sinn L, Sorichter S, Winkler J, Leuchte HH. [Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with commentary of the Cologne Consensus Conference 2010]. Dtsch Med Wochenschr. 2010 Oct;135 Suppl 3:S67-77. doi: 10.1055/s-0030-1263314. Epub 2010 Sep 22. German.
Background Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013 Jul 25;369(4):319-29. doi: 10.1056/NEJMoa1209657.
Background Pan Z, Marra AM, Benjamin N, Eichstaedt CA, Blank N, Bossone E, Cittadini A, Coghlan G, Denton CP, Distler O, Egenlauf B, Fischer C, Harutyunova S, Xanthouli P, Lorenz HM, Grunig E. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019 Oct 26;21(1):217. doi: 10.1186/s13075-019-1981-0.
Background Rubin LJ, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh A, Langleben D, Fritsch A, Menezes F, Davie N, Ghofrani HA. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-13. doi: 10.1183/09031936.00090614. Epub 2015 Jan 22.
Xanthouli P, Benjamin N, Coghlan G, Denton CP, Douschan P, Hachulla E, Halank M, Heberling M, Kovacs G, Lichtblau M, Marra AM, Steringer-Mascherbauer R, Ulrich S, Grunig E; ESRA investigators. Efficacy and safety of riociguat in early pulmonary vascular disease (ESRA): a prospective, multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Chest. 2026 Jul 15:S0012-3692(26)05971-4. doi: 10.1016/j.chest.2026.06.053. Online ahead of print.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Riociguat	Other / unclassified	2.5 mg	Oral