An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension
Condition: Hypertension, Pulmonary
MeSH terms: Hypertension, Pulmonary; Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a study to demonstrate the feasibility of an individual dose titration scheme based
      on the systolic blood pressure with a dose range from 1.0 mg TID to 2.5 mg TID. Patients
      suffering from chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial
      hypertension (PAH) will be included. After diagnosis by an expert center, patients receive
      medication three times a day starting with 1.0 mg TID. The first tablets are given in the
      hospital, then the patients are allowed to go home and take the medication at home. After 2
      weeks, patients return to the hospital for an ambulatory visit and the dose may be increased
      based on the actual condition of the patient (blood pressure and adverse events). Several
      measurements will be performed to test the efficacy of the drug and whether there are any
      unwanted reactions to the drug (blood tests, ECG, 6 minute walk test, imaging by Echo,
      quality of life scores). The dose of the drug will then be increased further until unwanted
      effects may occur or the blood pressure drops to low. The highest dose tested will be 2.5 mg
      TID. After 12 weeks the patient is going to stay in the hospital again and a right heart
      catheter is performed to examine the changes in hemodynamics after 12 weeks of treatment with
      the drug. If the patients give their consent they can enter a long-term extension trial
      continuing on BAY63-2521 with the dose reached after 12 weeks. Every 3 months an ambulatory
      visit at the specialist center will be performed including measurements of safety (blood
      tests, ECG, clinical assessment) and efficacy (6 minute walk test, Borg dyspnea scale, NT-pro
      BNP). Blood tests and ECG have been removed begin of 2013 as safety parameter by amendment 7;
      furthermore Borg dyspnea score and NT-proBNP have been removed as efficacy parameter.

      Initially the inclusion of ten patients suffering from chronic thromboembolic pulmonary
      hypertension (CTEPH) or pulmonary arterial hypertension (PAH) was planned. Later on the
      patient number was amended and 75 patients entered the trial.

      Furthermore the trial duration was extended and a long term treatment with BAY63-2521 was
      offered to the patients. Finally 68 patients moved over to the long term extension period of
      the trial.
    

Detailed description: 
      Specification of primary outcome measures for long-term safety and tolerability: Adverse
      events, blood pressure and heart rate, 12 lead ECG, clinical chemistry and hematology,
      Troponin I
    

Intervention name(s): Riociguat (Adempas, BAY63-2521)
Intervention type(s): Drug
Intervention description(s): Biweekly uptitration of BAY63-2521 (Oral sGC Stimulator) starting from 1.0 mg TID up to 2.5 mg TID in steps of +0.5 mg according to safety and tolerability.
Intervention MeSH terms: Riociguat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pulmonary Arterial Hypertension (PAH); Chronic Thromboembolic Pulmonary Hypertension (CTEPH)