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NCT01065454: LEPHT

A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction

Completed Phase 2 Results posted Last updated 28 August 2025
What this trial tests

Phase 2 trial testing Riociguat (Adempas, BAY63-2521) in Hypertension, Pulmonary in 202 participants. Completed in 23 July 2025.

Timeline
14 April 2010
Primary endpoint
6 June 2012
23 July 2025

Quick facts

Lead sponsorBayer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment202
Start date14 April 2010
Primary completion6 June 2012
Estimated completion23 July 2025
Sites83 locations across Denmark, France, Italy, Japan, Netherlands, Belgium, Austria, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

Adults 18 to 80, any sex, with Hypertension, Pulmonary or Ventricular Dysfunction, Left. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 Primary · Baseline and visit 6 (16 weeks)

Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-6.1± 9.68
Riociguat (Adempas, BAY63-2521) up to 1 mg-0.8± 8.41
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-4.5± 7.35
Placebo-4.0± 9.00
Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The mixed venous oxygen saturation rate (SvO2) is a directly measured hemodynamic parameter. SvO2 is recorded during a right heart catheterization.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg1.98± 7.084
Riociguat (Adempas, BAY63-2521) up to 1 mg0.46± 7.866
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-0.21± 5.969
Placebo1.28± 9.259
Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80\*(PAPmean - PCWP)/CO

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-78.15± 125.261
Riociguat (Adempas, BAY63-2521) up to 1 mg-33.05± 99.322
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-51.44± 124.107
Placebo-36.97± 157.523
Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The pulmonary vascular resistance index (PVRi) is a calculated hemodynamic parameter. PVRi is derived from the pulmonary vascular resistance (PVR) normalized by the body surface area (BSA). Formula: PVRi = 80\*(PAPmean - PCWP)\*BSA/CO

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-152.60± 250.366
Riociguat (Adempas, BAY63-2521) up to 1 mg-61.763± 202.138
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-91.65± 237.256
Placebo-76.47± 311.693
Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The systemic vascular resistance (SVR) is a calculated hemodynamic parameter. SVR is derived from the directly measured parameter mean right atrial pressure (RAPmean) and the calculated parameter mean systemic arterial pressure (SAPmean) divided by the cardiac output (CO). RAPmean is acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: SVR = 80\*(SAPmean - RAPmean)/CO

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-340.44± 394.87
Riociguat (Adempas, BAY63-2521) up to 1 mg-118.72± 369.865
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-67.46± 315.097
Placebo-94.37± 431.049
Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The systemic vascular resistance index (SVRi) is a calculated hemodynamic parameter. SVRi is derived from the systemic vascular resistance (SVR) normalized by the body surface area (BSA). Formula: SVRi = 80\*(SAPmean - RAPmean)\*BSA/CO

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-651.98± 757.617
Riociguat (Adempas, BAY63-2521) up to 1 mg-217.14± 742.465
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-100.31± 612.460
Placebo-195.11± 853.927
Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The transpulmonary pressure gradient (TPG) is a calculated hemodynamic parameter. TPG is calculated from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP). These 2 parameters are acquired during a right heart catheterization. Formula: TPG = PAPmean - PCWP

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-2.16± 4.795
Riociguat (Adempas, BAY63-2521) up to 1 mg-1.01± 5.224
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-1.65± 4.652
Placebo-1.37± 7.001
Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

Pulmonary capillary wedge pressure (PCWP) is a directly measured hemodynamic parameter acquired during a right heart catheterization.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-3.93± 9.381
Riociguat (Adempas, BAY63-2521) up to 1 mg0.25± 9.001
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-2.818± 7.842
Placebo-2.68± 7.791
Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg0.584± 2.344
Riociguat (Adempas, BAY63-2521) up to 1 mg1.140± 2.986
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg0.304± 2.109
Placebo0.393± 1.586
Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

Systolic pulmonary arterial pressure (PAPsyst) is a directly measured hemodynamic parameter acquired during a right heart catheterization.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg-7.69± 14.251
Riociguat (Adempas, BAY63-2521) up to 1 mg-2.89± 12.333
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg-5.86± 11.589
Placebo-4.49± 13.717
Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a non-invasive echocardiography examination. Formula: LEVF = 100\*(LVEDV - LVESV)/LVEDV

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg6.599± 43.187
Riociguat (Adempas, BAY63-2521) up to 1 mg12.659± 41.769
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg5.529± 48.322
Placebo11.121± 42.989
Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 Secondary · Baseline and visit 6 (16 weeks)

Left ventricular end-systolic volume (LVESV) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

GroupValue95% CI
Riociguat (Adempas, BAY63-2521) up to 2 mg1.805± 31.735
Riociguat (Adempas, BAY63-2521) up to 1 mg6.415± 28.832
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg1.507± 34.033
Placebo7.295± 32.311

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events occurring between the subject has signed the informed consent and 30 days after the definite stop of study medication (over a period approximately 25 months) were reported.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Riociguat (Adempas, BAY63-2521) up to 2 mg
Serious: 23/67 (34%)
Deaths:
Riociguat (Adempas, BAY63-2521) up to 1 mg
Serious: 7/33 (21%)
Deaths:
Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg
Serious: 7/32 (22%)
Deaths:
Placebo
Serious: 18/69 (26%)
Deaths:

Serious adverse events (60 terms)

ReactionSystemRiociguat (Adempas, BAY63-…Riociguat (Adempas, BAY63-…Riociguat (Adempas, BAY63-…Placebo
Cardiac failureCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiac failure congestiveCardiac disorders
Ventricular tachycardiaCardiac disorders
GastroenteritisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Cardiac failure chronicCardiac disorders
Cardiac tamponadeCardiac disorders
Coronary artery diseaseCardiac disorders
Right ventricular failureCardiac disorders
Sinus tachycardiaCardiac disorders
Ventricular fibrillationCardiac disorders
Abdominal pain upperGastrointestinal disorders
Gastritis erosiveGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
FaecalomaGastrointestinal disorders
CystGeneral disorders
HerniaGeneral disorders
PyrexiaGeneral disorders
General physical health deteriorationGeneral disorders
Medical device complicationGeneral disorders
Device malfunctionGeneral disorders
Other adverse events (155 terms — click to expand)

ReactionSystemRiociguat (Adempas, BAY63-…Riociguat (Adempas, BAY63-…Riociguat (Adempas, BAY63-…Placebo
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Blood creatinine increasedInvestigations
HypotensionVascular disorders
Upper respiratory tract infectionInfections and infestations
Atrial fibrillationCardiac disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
InfluenzaInfections and infestations
NasopharyngitisInfections and infestations
Blood urea increasedInvestigations
International normalised ratio increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
SomnolenceNervous system disorders
GastroenteritisInfections and infestations
Glomerular filtration rate decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Renal impairmentRenal and urinary disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
PalpitationsCardiac disorders
Supraventricular tachycardiaCardiac disorders
Ventricular tachycardiaCardiac disorders
HyperthyroidismEndocrine disorders
Abdominal pain upperGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Gastrointestinal painGastrointestinal disorders
Chest discomfortGeneral disorders
Chest painGeneral disorders

Most-reported serious reactions: Cardiac failure, Atrial fibrillation, Cardiac failure acute, Cardiac failure congestive, Ventricular tachycardia, Gastroenteritis, Anaemia, Cardiac arrest.

Data from ClinicalTrials.gov NCT01065454 adverse events section.

Sponsor's own description

The aim of this study is to assess whether increasing oral doses of Riociguat are safe and improve the well-being, symptoms and outcome in patients with pulmonary hypertension associated with left ventricular systolic dysfunction

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease.
    Stasch JP, Pacher P, Evgenov OV. · · 2011 · cited 462× · PMID 21606405 · DOI 10.1161/circulationaha.110.981738
  2. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study.
    Bonderman D, Ghio S, Felix SB, Ghofrani HA, et al · · 2013 · cited 231× · PMID 23775260 · DOI 10.1161/circulationaha.113.001458
  3. cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.
    Friebe A, Sandner P, Schmidtko A. · · 2020 · cited 102× · PMID 31853617 · DOI 10.1007/s00210-019-01779-z
  4. Riociguat: Clinical research and evolving role in therapy.
    Klinger JR, Chakinala MM, Langleben D, Rosenkranz S, et al · · 2021 · cited 27× · PMID 33242341 · DOI 10.1111/bcp.14676
  5. Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design.
    Ghio S, Bonderman D, Felix SB, Ghofrani HA, et al · · 2012 · cited 20× · PMID 22719060 · DOI 10.1093/eurjhf/hfs071
  6. A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function.
    Ameri P, Mercurio V, Pollesello P, Anker MS, et al · · 2024 · cited 12× · PMID 38639017 · DOI 10.1002/ejhf.3236
  7. At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy.
    Sulaiman A, Chambers J, Chilumula SC, Vinod V, et al · · 2022 · cited 4× · PMID 35326728 · DOI 10.3390/cancers14061577

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01065454.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing