check_circleStudy Completed

Hypertension, Pulmonary

An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension

Trial purpose

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.

Key Participants Requirements

Sex

Both

Age

18 - 65 Years
  • - Patients with CTEPH or PAH in NYHA class II or III
  • - Patients with PDE 5 inhibitor or prostacycline pretreatment, relevant pulmonary diseases, relevant cardiac diseases, severe coagulation disorders, moderate to severe hepatic or renal insufficiency, pregnancy, hypotension

Trial summary

Enrollment Goal
75
Trial Dates
January 2007 - September 2014
Phase
Phase 2
Could I Receive a placebo
No
Products
Adempas (Riociguat, BAY63-2521)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum Giessen und MarburgGießen, 35392, Germany
Completed
Universitätsklinikum Leipzig AöRLeipzig, 04103, Germany
Completed
Med. Fakultät der Martin-Luther-Universität Halle-WittenbergHalle, 06120, Germany
Completed
DRK Kliniken Berlin - KöpenickBerlin, 12559, Germany
Completed
Universitätsklinikum des SaarlandesHomburg, 66421, Germany
Completed
Klinikum der Ernst-Moritz-Arndt-UniversitätGreifswald, 17475, Germany
Completed
Medizinische Fakultät Carl Gustav CarusDresden, 01307, Germany
Completed
Kliniken der Medizinischen Hochschule HannoverHannover, 30625, Germany
Completed
Kerckhoff-Klinik GmbHBad Nauheim, 61231, Germany
Completed
LMU Klinikum der Universität München - GroßhadernMünchen, 81377, Germany
Completed
Universitätsklinikum HeidelbergHeidelberg, 69120, Germany
Completed
Universitätsklinikum Hamburg Eppendorf (UKE)Hamburg, 20246, Germany
Completed
Klinik Löwenstein gGmbHLöwenstein, 74245, Germany
Completed
Universitätsklinikum KölnKöln, 50924, Germany
Completed
Universitätsklinikum RegensburgRegensburg, 93042, Germany

Primary Outcome

  • To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure
    date_rangeTime Frame:
    3 months
    enhanced_encryption
    Safety Issue:
    yes
  • To investigate the long term safety and tolerability of BAY63-2521
    date_rangeTime Frame:
    max. 84 months
    enhanced_encryption
    Safety Issue:
    yes

Secondary Outcome

  • 6MWT
    date_rangeTime Frame:
    max. 84 months
    enhanced_encryption
    Safety Issue:
    no
  • Right heart catheter invasive hemodynamics
    date_rangeTime Frame:
    3 months
    enhanced_encryption
    Safety Issue:
    no
  • WHO functional class assessment
    date_rangeTime Frame:
    max. 84 months
    enhanced_encryption
    Safety Issue:
    no
  • NT-pro BNP
    date_rangeTime Frame:
    75 months
    enhanced_encryption
    Safety Issue:
    no
  • Imaging by echo
    date_rangeTime Frame:
    3 months
    enhanced_encryption
    Safety Issue:
    no

Trial design

A multicenter, non-randomized, non-blinded, noncontrolled study to investigate the impact of multiple doses of BAY 63-2521 on safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with pulmonary hypertension in a 12-week 3 times a day individual dose titration scheme
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1