An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension

NCT ID: NCT00454558

Last Updated: 2015-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2014-09-30

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.

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

Conditions

Hypertension, Pulmonary

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

Riociguat (Adempas, BAY63-2521)

Intervention Type: 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.

Interventions

Riociguat (Adempas, BAY63-2521)

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 Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Heidelberg, Baden-Wurttemberg, Germany

Löwenstein, Baden-Wurttemberg, Germany

München, Bavaria, Germany

Regensburg, Bavaria, Germany

Hamburg, City state of Hamburg, Germany

Bad Nauheim, Hesse, Germany

Giessen, Hesse, Germany

Hanover, Lower Saxony, Germany

Greifswald, Mecklenburg-Vorpommern, Germany

Cologne, North Rhine-Westphalia, Germany

Homburg, Saarland, Germany

Dresden, Saxony, Germany

Leipzig, Saxony, Germany

Halle, Saxony-Anhalt, Germany

Berlin, State of Berlin, Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 19705340 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20530034 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28610669 (View on PubMed)

Other Identifiers

2006-003520-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12166

Identifier Type: -

Identifier Source: org_study_id