Pulmonary Vascular DisorderPhase 2ESRANCT05339087
Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH
A Phase 2 study testing Riociguat Oral Tablet in people with Pulmonary Vascular Disorder and Primary Pulmonary Hypertension, run by Heidelberg University at 8 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Vascular Disorder, Primary Pulmonary Hypertension, Systemic Sclerosis
- What is being tested?
- Riociguat Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 24 Oct 2022to 31 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age at time of inclusion.
- Male and female patients with early pulmonary vascular disease, defined as either a) mean pulmonary arterial pressure (mPAP) ≥25 mmHg with pulmonary vascular resistance (PVR) ≥2 to <3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg or b) mPAP 21-<25 mmHg with PVR ≥2 WU, and PAWP ≤15 mmHg associated with connective tissue disease (CTD) or as idiopathic/heritable form (see Group I / Nice Clinical Classification of Pulmonary Hypertension) (acc. to Simonneau et al. 2019). Patients with rheumatoid arthritis or connective tissue disease of any kind, except systemic lupus erythematosus, may also be included. Patients in group b will be mainly enrolled as long as patients in group a are not defined as having pulmonary arterial hypertension according to European pulmonary hypertension guidelines.
- Treatment naïve patients (with respect to PAH specific medication)
- Unspecific treatments which may also be used for the treatment of pulmonary hypertension such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. Permitted are also treatments of the rheumatologic disease. However, these drugs must have been started at least 1 month before right heart catheterization.
- Right-heart catheterization results must not be older than 1 month at Visit 1 (will be considered as baseline values, the time frame can be prolonged up to 6 months, if the patient has had no signs of clinical changes defined as >10% change of 6MWD, WHO FC, > 30% change in NT-proBNP) and must have been measured in the participating center under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient's regular diagnostic work up, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent).
- Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovariectomy, and women with hysterectomy can be included in the study.
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- Women of childbearing potential can only be included in the study if all of the following applies (listed below):
- Negative serum pregnancy test at screening and at study start (visit 1).
- Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. These tests should be performed by the patient at home.
- Agreement to use a highly effective contraception method as specified from screening until at least 30 days after last dose of study medication.
- Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
- Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.
Who cannot join
- Patients with systemic lupus erythematosus.
- Concomitant PAH-targeted treatment is not allowed during the study.
- Concomitant treatment with phosphodiesterase 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues due to digital ulcers is contraindicated and must not be taken during the study period. Such drugs must have a washout-phase of 3 days at the time of right heart catheterization at screening. Intravenous treatment with prostacyclin analogues should not be performed within 1 week of right heart catheterization. Any decision to discontinue above-mentioned drugs will be made by the clinicians and the patient at screening, which takes part during the patients' regular routine visit. The discontinuation of above-mentioned drugs will be evaluated by considering the presence or absence of digital ulcers and their frequency of appearance in the patient's medical history.
- Pulmonary hypertension explained by other cause including group 2, 3, 4 and 5 PH according to the current guidelines.
- Cardiac comorbidity, defined with three or more of the following conditions: uncontrolled arterial hypertension, diabetes mellitus, body mass index >35, left atrial enlargement >20 cm², atrial fibrillation, left ventricular ejection fraction <50%.
- Pulmonary comorbidity, defined as forced vital capacity (FVC) ≤70; forced expiratory volume in 1 second (FEV1) ≤50%; diffusion capacity of the lung (DLCO) ≤40%. FVC may be <70/ if high resolution computed tomography shows <20% lung fibrosis.
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- Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator.
- Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g. active cancer disease with localized and/or metastasized tumor mass).
- Patients with a history of severe or multiple drug allergies (defined as allergic reactions to three or more structurally unrelated drugs).
- Patients with hypersensitivity to the investigational drug or any of the excipients.
- Contraindications according to summary of product characteristics of riociguat (e.g. arterial hypotension with systolic blood pressure <95 mmHg; nitrates)
- Participation in any clinical drug trial within 4 weeks prior to screening of this study and/or patient, who is scheduled to receive an investigational medicinal product (IMP) during the course of this study
- Background therapy with highly anti-fibrotic drugs (pirfenidone) or nintedanib, prednisolone >10 mg/day
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
Austria2 sites
LKH-Univ. Klinikum Graz Universitätsklinik für Innere Medizin Klinische Abteilung für Pulmonologie
Graz, 8036
Ordensklinikum Linz GmbH Elisabethinen
Linz, 4020
Germany2 sites
Carl Gustav Carus University Hospital at the TU Dresden, Medical Department I, Center for PH
Dresden
Centre for Pulmonary Hypertension at the Thoraxklinik Heidelberg, Heidelberg University Hospital Heidelberg
Heidelberg, 69126
France1 site
Centre de référence des Maladies Auto-Immunes Systémiques rares du Nord et Nord-Ouest (CeRAINO) Service de Médecine Interne et Immunologie Clinique Hôpital Claude Huriez, CHU
Lille, 59037
Italy1 site
Università Degli Studi Di Napoli Federico II Scuola Di Medicina E Chirurgia
Naples, 80131
Switzerland1 site
Universitätsspital Zürich Pulmonale Hypertonie, Klinik für Pneumologie
Zurich, 8091
About this study
Official 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 (ESRA)
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.
Read the 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
- Being tested
- Riociguat Oral Tablet, Placebo
- Keywords
- early pulmonary vascular disease, riociguat, pulmonary hypertension
- Medical subject headings
- Familial Primary Pulmonary Hypertension, Scleroderma, Systemic, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat Oral TabletDrug
Also called MK-4836, ATC Code: C02KX05
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
PlaceboOther
Sham titration and adjustment to maintenance dose will be performed according to individual tolerability as in the experimental arm.
| Study group | Role | What they receive |
|---|---|---|
| Riociguat | Experimental | patients will undergo a titration phase starting with 1mg riociguat oral tablets tid (three times daily) up to a maximum dosage of 2.5mg tid that will be continued for the remainder of the study. Receives: Drug: Riociguat Oral Tablet |
| Placebo | Placebo comparator | Placebo tablets with the same treatment regimen (tid) as the verum therapy will be provided. Patients will undergo a sham titration phase with sham doses individually adjusted as in the experimental arm Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Pulmonary Vascular Resistance (PVR)
Change in pulmonary hemodynamics assessed by right heart catheterization
Measured: baseline, 24 weeks
Secondary outcomes (5)
Change of Cardiac Index (CI) at Rest From Baseline at 24 Weeks
Change in pulmonary hemodynamics assessed by right heart catheterization
Measured: baseline, 24 weeks
Change of Total Pulmonary Resistance (TPR) From Baseline at 24 Weeks
Change in Pulmonary hemodynamics assessed by right heart catheterization
Hierarchical testing of secondary endpoints stopped after first step.
Measured: baseline, 24 weeks
Change of Diffusion Capacity of the Lung (DLCO) From Baseline at 24 Weeks
Change assessed by lung function tests.
Hierarchical testing of secondary endpoints stopped after first step.
Measured: baseline, 24 weeks
Change in 6-minute Walking Distance (6MWD)
Change in exercise capacity assessed by 6-minute walking distance test
Hierarchical testing of secondary endpoints stopped after first step.
Measured: baseline, 24 weeks
Change of World Health Organization- Functional Class (WHO-FC) From Baseline at 24 Weeks
Change of WHO functional class, change score The World Health Organization (WHO) functional class (FC) describes the severity of pulmonary hypertension (PH) symptoms. FC I is considered the mildest and FC IV the most severe form of PH.
Measured: baseline, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2022
- Study start24 Oct 2022
- Primary completion31 Jul 2025
- Study completion31 Jul 2025
Why it stopped: Strategic re-prioritization by the IMP supplier. Decision not safety-related.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Vascular DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Prof. Dr. med. Ekkehard Gruenig, Heidelberg University
- Investigators
- Ekkehard Grünig, MD, Principal investigator, Thoraxklinik at the University of Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05339087
- Sponsor's protocol ID
- 2020-01RCT
- Acronym
- ESRA
- Status last verified
- Jan 2026
- First submitted
- 14 Apr 2022
- Last updated
- 21 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26837729Grunig 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.
PubMed 20862623Ghofrani 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.
PubMed 23883377Pan 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.
PubMed 31655622Rubin 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.
PubMed 25614164Xanthouli 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: A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial. Chest. 2026 Jul 15:S0012-3692(26)05971-4. doi: 10.1016/j.chest.2026.06.053. Online ahead of print.
PubMed 42457022
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 (ESRA)
- ClinicalTrials.gov ID
- NCT05339087
- Acronym / sponsor ID
- ESRA / 2020-01RCT
- Conditions
- Pulmonary Vascular Disorder, Primary Pulmonary Hypertension, Systemic Sclerosis, Other Systemic Involvement of Connective Tissue
- Keywords
- early pulmonary vascular disease, riociguat, pulmonary hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic re-prioritization by the IMP supplier. Decision not safety-related.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 21 Apr 2022 (actual)
- Results
- Posted 21 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Riociguat | Experimental | Drug: Riociguat Oral Tabletpatients will undergo a titration phase starting with 1mg riociguat oral tablets tid (three times daily) up to a maximum dosage of 2.5mg tid that will be continued for the remainder of the study. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo tablets with the same treatment regimen (tid) as the verum therapy will be provided. Patients will undergo a sham titration phase with sham doses individually adjusted as in the experimental arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ≥18 years of age at time of inclusion.
- Male and female patients with early pulmonary vascular disease, defined as either a) mean pulmonary arterial pressure (mPAP) ≥25 mmHg with pulmonary vascular resistance (PVR) ≥2 to <3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg or b) mPAP 21-<25 mmHg with PVR ≥2 WU, and PAWP ≤15 mmHg associated with connective tissue disease (CTD) or as idiopathic/heritable form (see Group I / Nice Clinical Classification of Pulmonary Hypertension) (acc. to Simonneau et al. 2019). Patients with rheumatoid arthritis or connective tissue disease of any kind, except systemic lupus erythematosus, may also be included. Patients in group b will be mainly enrolled as long as patients in group a are not defined as having pulmonary arterial hypertension according to European pulmonary hypertension guidelines.
- Treatment naïve patients (with respect to PAH specific medication)
- Unspecific treatments which may also be used for the treatment of pulmonary hypertension such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. Permitted are also treatments of the rheumatologic disease. However, these drugs must have been started at least 1 month before right heart catheterization.
- Right-heart catheterization results must not be older than 1 month at Visit 1 (will be considered as baseline values, the time frame can be prolonged up to 6 months, if the patient has had no signs of clinical changes defined as >10% change of 6MWD, WHO FC, > 30% change in NT-proBNP) and must have been measured in the participating center under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient's regular diagnostic work up, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent).
Key exclusion criteria (13 listed)
- Patients with systemic lupus erythematosus.
- Concomitant PAH-targeted treatment is not allowed during the study.
- Concomitant treatment with phosphodiesterase 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues due to digital ulcers is contraindicated and must not be taken during the study period. Such drugs must have a washout-phase of 3 days at the time of right heart catheterization at screening. Intravenous treatment with prostacyclin analogues should not be performed within 1 week of right heart catheterization. Any decision to discontinue above-mentioned drugs will be made by the clinicians and the patient at screening, which takes part during the patients' regular routine visit. The discontinuation of above-mentioned drugs will be evaluated by considering the presence or absence of digital ulcers and their frequency of appearance in the patient's medical history.
- Pulmonary hypertension explained by other cause including group 2, 3, 4 and 5 PH according to the current guidelines.
- Cardiac comorbidity, defined with three or more of the following conditions: uncontrolled arterial hypertension, diabetes mellitus, body mass index >35, left atrial enlargement >20 cm², atrial fibrillation, left ventricular ejection fraction <50%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riociguat Oral TabletAlso: MK-4836, ATC Code: C02KX05Riociguat 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 | Drug | Riociguat |
| PlaceboSham titration and adjustment to maintenance dose will be performed according to individual tolerability as in the experimental arm. | Other | Placebo |
Primary outcome
Change of Pulmonary Vascular Resistance (PVR)
Time frame: baseline, 24 weeks
Change in pulmonary hemodynamics assessed by right heart catheterization
5 secondary outcomes
Change of Cardiac Index (CI) at Rest From Baseline at 24 Weeks
Time frame: baseline, 24 weeks
Change of Total Pulmonary Resistance (TPR) From Baseline at 24 Weeks
Time frame: baseline, 24 weeks
Change of Diffusion Capacity of the Lung (DLCO) From Baseline at 24 Weeks
Time frame: baseline, 24 weeks
Change in 6-minute Walking Distance (6MWD)
Time frame: baseline, 24 weeks
Change of World Health Organization- Functional Class (WHO-FC) From Baseline at 24 Weeks
Time frame: baseline, 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26837729Galie 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: PubMed 20862623Grunig 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: PubMed 23883377Ghofrani 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: PubMed 31655622Pan 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: PubMed 25614164Rubin 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.
- Derived from this study: PubMed 42457022Xanthouli 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: A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial. Chest. 2026 Jul 15:S0012-3692(26)05971-4. doi: 10.1016/j.chest.2026.06.053. Online ahead of print.
- Individual participant dataSharing planned: No
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Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ekkehard Grünig, MD principal investigator
Thoraxklinik at the University of Heidelberg
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riociguat Oral Tablet in people with Pulmonary Vascular Disorder and Primary Pulmonary Hypertension, run by Heidelberg University at 8 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Austria, Germany, France, Italy, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Pulmonary Vascular Resistance (PVR) (time frame: baseline, 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05339087, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.