Trial Condition(s):

Pulmonary arterial hypertension

Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy (REPLACE)

Bayer Identifier:

18588

ClinicalTrials.gov Identifier:

NCT02891850

EudraCT Number:

2016-001067-36

Study Completed

Trial Purpose

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

Inclusion Criteria
- 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.
Exclusion Criteria
- 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
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Phase
4
Could I receive a placebo?
No
Products
Adempas (Riociguat, BAY63-2521)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Investigative Site

Köln, Germany, 50937

Status
Completed
 
Locations

Investigative Site

Gießen, Germany, 35390

Status
Completed
 
Locations

Investigative Site

Hannover, Germany, 30625

Status
Completed
 
Locations

Investigative Site

München, Germany, 81377

Status
Completed
 
Locations

Investigative Site

Leipzig, Germany, 04103

Status
Completed
 
Locations

Investigative Site

Heidelberg, Germany, 69126

Status
Completed
 
Locations

Investigative Site

Hamburg, Germany, 20246

Status
Completed
 
Locations

Investigative Site

Clydebank, United Kingdom, G81 4DY

Status
Completed
 
Locations

Investigative Site

London, United Kingdom, SW3 6NP

Status
Completed
 
Locations

Investigative Site

Le Kremlin-Bicêtre, France, 94270

Status
Completed
 
Locations

Investigative Site

Rouen, France, 76031

Status
Completed
 
Locations

Investigative Site

Pavia, Italy, 27100

Status
Completed
 
Locations

Investigative Site

Roma, Italy, 00161

Status
Completed
 
Locations

Investigative Site

Barcelona, Spain, 08036

Status
Completed
 
Locations

Investigative Site

Barcelona, Spain, 08035

Status
Completed
 
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Investigative Site

AMSTERDAM, Netherlands, 1081 HV

Status
Completed
 
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Investigative Site

NIJMEGEN, Netherlands, 6500HB

Status
Completed
 
Locations

Investigative Site

Coimbra, Portugal, 3000-075

Status
Completed
 
Locations

Investigative Site

Lisboa, Portugal, 1649-035

Status
Completed
 
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Investigative Site

Istanbul, Turkey, 34-300

Status
Completed
 
Locations

Investigative Site

Chaidari, Greece, 124 62

Status
Completed
 
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Investigative Site

Thessaloniki, Greece, 57010

Status
Completed
 
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Investigative Site

Seoul, South Korea, 03722

Status
Completed
 
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Investigative Site

Mexico D.F., Mexico, 14080

Status
Completed
 
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Investigative Site

Graz, Austria, 8036

Status
Completed
 
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Investigative Site

Izmir, Turkey, 34098

Status
Completed
 
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Investigative Site

Thessaloniki, Greece, 546 36

Status
Completed
 
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Investigative Site

Seoul, South Korea, 138-736

Status
Completed
 
Locations

Investigative Site

Seoul, South Korea, 135-710

Status
Completed
 
Locations

Investigative Site

Seoul, South Korea, 110-744

Status
Completed
 
Locations

Investigative Site

Toledo, Spain, 45004

Status
Completed
 
Locations

Investigative Site

Dresden, Germany, 01307

Status
Completed
 
Locations

Investigative Site

Homburg, Germany, 66421

Status
Completed
 
Locations

Investigative Site

Würzburg, Germany, 97074

Status
Completed
 
Locations

Investigative Site

München, Germany, 80639

Status
Completed
 
Locations

Investigative Site

Nagoya, Japan, 467-8602

Status
Completed
 
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Investigative Site

Sendai, Japan, 980-8574

Status
Completed
 
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Investigative Site

Bunkyo-ku, Japan, 113-8655

Status
Completed
 
Locations

Investigative Site

Palermo, Italy, 90127

Status
Completed
 
Locations

Investigative Site

Montreal, Canada, H3T 1E2

Status
Completed
 
Locations

Investigative Site

LEUVEN, Belgium, 3000

Status
Completed
 
Locations

Investigative Site

Culiacan, Mexico, 80020

Status
Completed
 
Locations

Investigative Site

Aarhus N, Denmark, 8200

Status
Completed
 
Locations

Investigative Site

Almada, Portugal, 2801-951

Status
Completed
 
Locations

Investigative Site

Taipei, Taiwan, China, 10016

Status
Completed
 
Locations

Investigative Site

Kaoshiung, Taiwan, China, 81346

Status
Completed
 
Locations

Investigative Site

London, United Kingdom, NW3 2QG

Status
Completed
 
Locations

Investigative Site

Sacramento, United States, 95817

Status
Completed
 
Locations

Investigative Site

Dallas, United States, 75390

Status
Completed
 
Locations

Investigative Site

Weston, United States, 33331

Status
Completed
 
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Investigative Site

Tucson, United States, 85724

Status
Completed
 
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Investigative Site

Rochester, United States, 14623

Status
Completed
 
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Investigative Site

New York, United States, 10003

Status
Completed
 
Locations

Investigative Site

Cleveland, United States, 44195

Status
Completed
 
Locations

Investigative Site

Louisville, United States, 40202

Status
Completed
 
Locations

Investigative Site

Nashville, United States, 37232

Status
Completed
 
Locations

Investigative Site

Detroit, United States, 48202

Status
Completed
 
Locations

Investigative Site

Kansas City, United States, 66103

Status
Completed
 
Locations

Investigative Site

Newark, United States, 07112

Status
Completed
 
Locations

Investigative Site

Mineola, United States, 11501

Status
Completed
 
Locations

Investigative Site

Sao Paulo, Brazil, 04023-061

Status
Completed
 
Locations

Investigative Site

Las Palmas de Gran Canaria, Spain, 35020

Status
Completed
 
Locations

Investigative Site

Phoenix, United States, 85012

Status
Completed
 
Locations

Investigative Site

Tainan, Taiwan, China, 704

Status
Completed
 
Locations

Investigative Site

Lübeck, Germany, 23538

Status
Completed
 
Locations

Investigative Site

Praha 2, Czech Republic, 12808

Status
Completed
 
Locations

Investigative Site

Praha 4, Czech Republic, 140 21

Status
Completed
 
Locations

Investigative Site

Porto Alegre, Brazil, 90050-170

Status
Completed
 
Locations

Investigative Site

Belo Horizonte, Brazil, 30130-100

Status
Completed
 
Locations

Investigative Site

Sao Paulo, Brazil, 05403-000

Status
Completed
 
Locations

Investigative Site

Belo Horizonte, Brazil, 30441-070

Status
Completed
 
Locations

Investigative Site

Sheffield, United Kingdom, S10 2JF

Status
Completed
 
Locations

Investigative Site

Berlin, Germany, 14050

Status
Completed
 
Locations

Investigative Site

Blumenal, Brazil, 89030-101

Status
Completed
 
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Investigative Site

Napoli, Italy, 80131

Status
Completed
 
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Investigative Site

Istanbul, Turkey, 34093

Status
Completed
 
Locations

Investigative Site

Ankara, Turkey, 06100

Status
Completed
 
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Investigative Site

Wroclaw, Poland, 51-124

Status
Completed
 
Locations

Investigative Site

Orlando, United States, 32803

Status
Completed
 
Locations

Investigative Site

Troy, United States, 48085

Status
Completed
 
Locations

Investigative Site

Richmond, United States, 23225

Status
Completed
 

Trial Design