check_circleStudy Completed

pulmonary arterial hypertension

Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy

Trial purpose

To demonstrate the effectiveness of riociguat as replacement of phosphodiesterase-5 inhibitors (PDE-5i) therapy in pulmonary arterial hypertension (PAH) patients

Key Participants Requirements

Sex

Both

Age

18 - 75 Years
  • - Male and female patients aged 18 to 75 years.
    - Patients with symptomatic PAH with a pulmonary vascular resistance (PVR) > 400 dyn*sec*cm-5, mean pulmonary artery pressure ≥ 25 mmHg, and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg as assessed by the most recent right heart catheterization (RHC) from medical history prior to screening to confirm the diagnosis. Alternatively, PCWP can be replaced by left ventricular end-diastolic pressure (≤ 15 mmHg). PAH of the following types:
     -- Idiopathic
     -- Hereditary
     -- Drug and toxin induced PAH
     -- Associated with PAH due to:
     --- Connective tissue disease (CTD)
     --- Congenital heart disease, but only if the patient underwent surgical repair more than one year before enrolment
     --- Portal hypertension with liver cirrhosis (Note: patients with clinical relevant hepatic dysfunction are excluded; see exclusions related to disorders in organ function)
    - Patients who are on stable doses of a PDE-5i and ERA combination therapy or on stable PDE-5i monotherapy 6 weeks prior to and at randomization but not at treatment goal (tadalafil 20 to 40 mg once daily or sildenafil at least 60 mg daily dose).
    - WHO FC III at screening and at randomization.
    - 6MWD test between 165 m and 440 m at screening and at randomization.
    - Stable dose of diuretics, if used, for at least 30 days prior to and at randomization.
    - Patients who are able to understand and follow instructions and who are able to participate in the study for the entire study.
    - Women of childbearing potential must agree to use adequate contraception when sexually active. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies beginning with signing of the informed consent form until 30 (+5) days after the last administration of study drug.
    - 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.
  • - Participation in another interventional clinical study within 30 days prior to screening.
    - All types of PH (including PH-IIP) except subtypes of Dana Point Group I specified in the inclusion criteria.
    - Previous treatment with riociguat.
    - Pregnant women (i.e., positive serum ß-human-chorionic-gonadotropin test or other signs of pregnancy), or breast feeding women, or women with childbearing potential not using a combination of 2 effective contraception methods (as laid out in inclusion criterion) throughout the study.
    - 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.
    - Relevant obstructive and restrictive or other lung diseases.
    - 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).
    - Cardiovascular exclusion criteria like left ventricular disease, coronary heart disease or stroke within previous 3 months.
    - Patients with hypersensitivity to the investigational drug or any of the excipients.
    - Patients unable to perform a valid 6MWD test (e.g., orthopedic disease, peripheral artery occlusive disease, which affects the patient’s ability to walk). Note: Patients, who require walking aids, may be included if in the opinion of the investigator the walking distance is not impaired. Patients with a variance of more than 15% between the screening and the randomization (i.e., baseline) 6MWD test.

Trial summary

Enrollment Goal
225
Trial Dates
January 2017 - March 2020
Phase
Phase 4
Could I Receive a placebo
No
Products
Adempas (Riociguat, BAY63-2521)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Köln, 50937, Germany
Completed
Gießen, 35390, Germany
Completed
Hannover, 30625, Germany
Completed
München, 81377, Germany
Completed
Leipzig, 04103, Germany
Completed
Heidelberg, 69126, Germany
Completed
Hamburg, 20246, Germany
Completed
Clydebank, G81 4DY, United Kingdom
Completed
London, SW3 6NP, United Kingdom
Completed
Le Kremlin-Bicêtre, 94270, France
Completed
Rouen, 76031, France
Completed
Pavia, 27100, Italy
Completed
Roma, 00161, Italy
Completed
Barcelona, 08036, Spain
Completed
Barcelona, 08035, Spain
Withdrawn
BRUXELLES - BRUSSEL, 1070, Belgium
Completed
AMSTERDAM, 1081 HV, Netherlands
Completed
NIJMEGEN, 6500HB, Netherlands
Completed
Coimbra, 3000-075, Portugal
Completed
Lisboa, 1649-035, Portugal
Withdrawn
Wien, 1090, Austria
Completed
Istanbul, 34-300, Turkey
Completed
Chaidari, 124 62, Greece
Completed
Thessaloniki, 57010, Greece
Completed
Seoul, 03722, Korea, Republic Of
Withdrawn
Madrid, 28041, Spain
Withdrawn
Barcelona, 08003, Spain
Completed
Mexico D.F., 14080, Mexico
Withdrawn
Innsbruck, 6020, Austria
Completed
Graz, 8036, Austria
Completed
Izmir, 34098, Turkey
Completed
Thessaloniki, 546 36, Greece
Completed
Seoul, 138-736, Korea, Republic Of
Completed
Seoul, 135-710, Korea, Republic Of
Completed
Seoul, 110-744, Korea, Republic Of
Completed
Toledo, 45004, Spain
Completed
Dresden, 01307, Germany
Completed
Homburg, 66421, Germany
Completed
Würzburg, 97074, Germany
Completed
München, 80639, Germany
Completed
Nagoya, 467-8602, Japan
Completed
Sendai, 980-8574, Japan
Completed
Bunkyo-ku, 113-8655, Japan
Completed
Palermo, 90127, Italy
Withdrawn
Toronto, M5G 2N2, Canada
Withdrawn
Vancouver, V5Z 1M9, Canada
Completed
Montreal, H3T 1E2, Canada
Withdrawn
Calgary, T1Y 6J4, Canada
Completed
LEUVEN, 3000, Belgium
Completed
Culiacan, 80020, Mexico
Completed
Aarhus N, 8200, Denmark
Completed
Almada, 2801-951, Portugal
Completed
Taipei, 10016, Taiwan
Completed
Kaoshiung, 81346, Taiwan
Withdrawn
Cambridge, CB23 3RE, United Kingdom
Completed
London, NW3 2QG, United Kingdom
Completed
Sacramento, 95817, United States
Withdrawn
Columbus, 43210-1240, United States
Completed
Dallas, 75390, United States
Withdrawn
Boston, 02118, United States
Withdrawn
Boston, 02111, United States
Withdrawn
Falls Church, 22042, United States
Withdrawn
Milwaukee, 53215, United States
Withdrawn
Pittsburgh, 15212, United States
Completed
Weston, 33331, United States
Completed
Tucson, 85724, United States
Withdrawn
St, Louis, 63110, United States
Completed
Rochester, 14623, United States
Completed
New York, 10003, United States
Completed
Cleveland, 44195, United States
Completed
Louisville, 40202, United States
Withdrawn
Boston, 02114-2696, United States
Withdrawn
Chicago, 60612, United States
Withdrawn
Seattle, 98195, United States
Completed
Nashville, 37232, United States
Completed
Detroit, 48202, United States
Completed
Kansas City, 66103, United States
Withdrawn
New Haven, 06520, United States
Withdrawn
Oak Lawn, 60453, United States
Completed
Newark, 07112, United States
Withdrawn
Chapel Hill, 27599, United States
Completed
Mineola, 11501, United States
Withdrawn
Lille Cedex, 59037, France
Withdrawn
GRENOBLE Cedex 09, 38043, France
Withdrawn
BESANCON, 25030, France
Withdrawn
Camperdown, 2050, Australia
Withdrawn
Chermside, 4032, Australia
Completed
Sao Paulo, 04023-061, Brazil
Withdrawn
Genève, 1205, Switzerland
Withdrawn
Zürich, 8091, Switzerland
Completed
Las Palmas de Gran Canaria, 35020, Spain
Completed
Phoenix, 85012, United States
Completed
Tainan, 704, Taiwan
Withdrawn
Ann Arbor, 48109-0330, United States
Completed
Lübeck, 23538, Germany
Completed
Praha 2, 12808, Czech Republic
Completed
Praha 4, 140 21, Czech Republic
Withdrawn
Rio de Janeiro, 21941-913, Brazil
Completed
Porto Alegre, 90050-170, Brazil
Completed
Belo Horizonte, 30130-100, Brazil
Completed
Sao Paulo, 05403-000, Brazil
Withdrawn
Brasília, 70840 901, Brazil
Completed
Belo Horizonte, 30441-070, Brazil
Completed
Sheffield, S10 2JF, United Kingdom
Completed
Berlin, 14050, Germany
Withdrawn
Orlando, 32803, United States
Completed
Blumenal, 89030-101, Brazil
Withdrawn
Salamanca, 37007, Spain
Completed
Napoli, 80131, Italy
Completed
Istanbul, 34093, Turkey
Completed
Ankara, 06100, Turkey
Withdrawn
Otwock, 05-400, Poland
Withdrawn
Lodz, 91-347, Poland
Completed
Wroclaw, 51-124, Poland
Completed
Orlando, 32803, United States
Completed
Troy, 48085, United States
Completed
Richmond, 23225, United States
Withdrawn
Madrid, 28034, Spain
Withdrawn
Bath, BA1 3NG, United Kingdom
Withdrawn
København Ø, 2100, Denmark

Primary Outcome

  • Efficacy (Y/N)
    The treatment is assessed efficient in case at least 2 out of the following 3 criteria were fulfilled •6 Minute Walking Distance increase by ≥ 10% or ≥ 30 m from baseline to Week 24 •World Health Organization Functional Class (WHO FC) I or II at Week 24 •N-terminal pro-brain natriuretic peptide (NT-proBNP) reduction ≥ 30% from baseline to Week 24 (NT-proBNP ratio Week 24/baseline ≤ 0.7) and in absence of the defined criteria of clinical worsening
    date_rangeTime Frame:
    at Week 24
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Change in 6 Minute Walking Distance (6MWD) from baseline to 24 weeks
    date_rangeTime Frame:
    Baseline and Week 24
    enhanced_encryption
    Safety Issue:
    No
  • Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 24 weeks
    date_rangeTime Frame:
    Baseline and Week 24
    enhanced_encryption
    Safety Issue:
    No
  • Change in World Health Organization Functional Class (WHO FC) from baseline to 24 weeks
    date_rangeTime Frame:
    Baseline and Week 24
    enhanced_encryption
    Safety Issue:
    No
  • Change in clinical worsening from baseline to 24 weeks
    Definition of clinical worsening: 1) Death of any cause 2) Hospitalization due to worsening PAH (adjudicated): - Non-elective hospitalization due to PAH, or - Initiation of intravenous/subcutaneous prostanoid therapy. 3) Disease progression (adjudicated): - 6MWD decrease ≥ 15% from baseline (2 measurements on 2 separate days), and - Worsening in WHO FC. OR - 6MWD decrease ≥ 15% (2 measurements on 2 separate days), and - Need of new PAH-targeted medication or decompensated right sided heart failure.
    date_rangeTime Frame:
    Baseline and Week 24
    enhanced_encryption
    Safety Issue:
    Yes

Trial design

A prospective, randomized, international, multicenter, double-arm, controlled, open-label study of Riociguat in patients with pulmonary arterial hypertension (PAH) who are on a stable dose of phosphodiesterase-5 inhibitors (PDE-5i) with or without endothelin receptor antagonist (ERA), but not at treatment goal
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Open Label
Assignment
Parallel Assignment
Trial Arms
2