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

• Status: Completed
• Trial end date: 2020-03-03
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bayer
• Treatments: Endothelin Receptor Antagonists; Phosphodiesterase 5 Inhibitors; Riociguat; Sildenafil Citrate; Tadalafil

Criteria

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.