NCT00454558

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2007

Longer than P75 for phase_2

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2007

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 28, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 30, 2007

Completed
7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
Last Updated

October 16, 2015

Status Verified

September 1, 2015

Enrollment Period

7.5 years

First QC Date

March 28, 2007

Last Update Submit

October 14, 2015

Conditions

Hypertension, Pulmonary

Keywords

Pulmonary Arterial Hypertension (PAH)Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Outcome Measures

Primary Outcomes (2)

  • To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure

    3 months

  • To investigate the long term safety and tolerability of BAY63-2521

    max. 84 months

Secondary Outcomes (5)

  • 6MWT

    max. 84 months

  • Right heart catheter invasive hemodynamics

    3 months

  • WHO functional class assessment

    max. 84 months

  • NT-pro BNP

    75 months

  • Imaging by echo

    3 months

Study Arms (1)

Arm 1

EXPERIMENTAL
Drug: Riociguat (Adempas, BAY63-2521)

Interventions

Riociguat (Adempas, BAY63-2521)DRUG

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.

Arm 1

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with CTEPH or PAH in NYHA class II or III

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Unknown Facility

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Unknown Facility

Löwenstein, Baden-Wurttemberg, 74245, Germany

Location

Unknown Facility

München, Bavaria, 81377, Germany

Location

Unknown Facility

Regensburg, Bavaria, 93042, Germany

Location

Unknown Facility

Hamburg, Hamburg, 20246, Germany

Location

Unknown Facility

Bad Nauheim, Hesse, 61231, Germany

Location

Unknown Facility

Giessen, Hesse, 35392, Germany

Location

Unknown Facility

Hanover, Lower Saxony, 30625, Germany

Location

Unknown Facility

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

Unknown Facility

Cologne, North Rhine-Westphalia, 50924, Germany

Location

Unknown Facility

Homburg, Saarland, 66421, Germany

Location

Unknown Facility

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Leipzig, Saxony, 04103, Germany

Location

Unknown Facility

Halle, Saxony-Anhalt, 06120, Germany

Location

Unknown Facility

Berlin, State of Berlin, 12559, Germany

Location

Related Publications (3)

  • Belik J. Riociguat, an oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension. Curr Opin Investig Drugs. 2009 Sep;10(9):971-9.

    PMID: 19705340RESULT

  • Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, Ewert R, Weimann G, Grimminger F. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J. 2010 Oct;36(4):792-9. doi: 10.1183/09031936.00182909. Epub 2010 Jun 7.

    PMID: 20530034RESULT

  • Halank M, Hoeper MM, Ghofrani HA, Meyer FJ, Stahler G, Behr J, Ewert R, Fletcher M, Colorado P, Nikkho S, Grimminger F. Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study. Respir Med. 2017 Jul;128:50-56. doi: 10.1016/j.rmed.2017.05.008. Epub 2017 May 16.

    PMID: 28610669DERIVED

MeSH Terms

Conditions

Hypertension, PulmonaryPulmonary Arterial Hypertension

Interventions

riociguat

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesHypertensionVascular DiseasesCardiovascular Diseases

Study Officials

  • Bayer Study Director

    Bayer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2007

First Posted

March 30, 2007

Study Start

January 1, 2007

Primary Completion

July 1, 2014

Study Completion

September 1, 2014

Last Updated

October 16, 2015

Record last verified: 2015-09

Locations

DE(15)