Clinical Trial: Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 Phosphod

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

Detailed Summary:

Data from a previous single arm study (RESPITE) indicate that transition from PDE5i to riociguat may be feasible, safe and beneficial in patients not adequately responding to PDE5i.

REPLACE is a randomized controlled study to confirm the potential clinical benefit of transition from PDE5i to riociguat. Satisfactory clinical response in patients who are on a stable dose of phosphodiesterase-5inhibitors (PDE-5i) with or without endothelin receptor antagonist (ERA), but not at treatment goal will be compared between one group of patients randomized to maintain current treatment and another group where the PDE5i is replaced by riociguat.


Sponsor: Bayer

Current Primary Outcome: Efficacy (Y/N) [ Time Frame: at Week 24 ]

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



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in 6 Minute Walking Distance (6MWD) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in World Health Organization Functional Class (WHO FC) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in clinical worsening from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]

    Clinical Worsening:

    • Death of any cause.
    • Hospitalization due to worsening PAH (adjudicated):
    • Non-elective hospitalization due to PAH, or
    • Initiation of intravenous/subcutaneous prostanoid therapy.
    • 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.


Original Secondary Outcome:

  • Change in 6 Minute Walking Distance (6MWD) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in World Health Organization Functional Class (WHO FC) from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]
  • Change in clinical worsening from baseline to 24 weeks [ Time Frame: Baseline and Week 24 ]

    Clinical Worsening:

    • Death of any cause
    • Hospitalization due to worsening PAH (adjudicated):
    • Non-elective hospitalization due to PAH, or
    • Initiation of intravenous/subcutaneous prostanoid therapy.
    • 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.


Information By: Bayer

Dates:
Date Received: August 26, 2016
Date Started: January 12, 2017
Date Completion: July 31, 2018
Last Updated: May 17, 2017
Last Verified: May 2017