BAY63-2521 - Long-term Extension Study in Patients With Chronic Thromboembolic Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

— CHEST-2  

Official title:

Long-term Extension, Multicentre, Multi-international Study to Evaluate the Safety and Tolerability of Oral BAY63-2521 (1mg, 1.5 mg, 2.0 mg, 2.5 mg Tid) in Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910429
• Other study ID #: 11349
• Secondary ID: 2008-003539-19
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2009
• Est. completion date: August 19, 2019

Study information

• Verified date: November 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients who have completed the 16 weeks treatment of the CHEST-1 trial (study number 11348) will be asked to participate in this long term extension study with BAY63-2521. The aim of the long term study is to collect additional information to evaluate the safety and tolerability of BAY63-2521. Patients will be treated with open label medication on their individual optimal dose between 0,5 mg - 2,5 mg tid.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: August 19, 2019
• Est. primary completion date: August 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients who have completed 16 weeks of treatment in the double blind trial CHEST 1

Exclusion Criteria:

• Patients who have an ongoing serious adverse event from CHEST 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Riociguat (Adempas, BAY63-2521)
BAY63-2521 - 1 mg tid - 2,5 mg tid orally until end of study

Locations

Country	Name	City	State
Israel	Rabin Medical Center - Beilinson Campus	Petach Tikva
Portugal	Centro Hospitalar de Lisboa Norte - Hospital Santa Maria	Lisboa

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (2)

Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani HA, Hoeper MM, Lambelet M, Rahner C, Bansilal S, Nikkho S, Meier C, Sitbon O. Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study. J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28. — View Citation

Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris PA, Lambelet M, Nikkho S, Meier C, Hoeper MM. Application of the REVEAL risk score calculator 2.0 in the CHEST study. Respir Med. 2022 Apr-May;195:106783. doi: 10.1016/j.rmed.2022.106783. Epub 2022 Mar 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of Systolic Blood Pressure (SBP)	SBP was measured after the participant had been at rest for 10 minutes in a supine position. Low SBP was defined as SBP <95 mmHg, normal SBP as SBP 95-140mmHg, and high SBP as SBP >140 mmHg. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Diastolic Blood Pressure (DBP)	DBP was measured after the participants had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Heart Rate	Heart rate was measured after the participant had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Weight	Weight was evaluated for safety. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Oxygen Saturation (SaO2)	SaO2 is one parameters of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Arterial Partial Oxygen Pressure (PaO2)	PaO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)	PaCO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Other	Change of RR Duration From Electrocardiogram (ECG)	Heart rate from ECG is derived from the RR duration, unless arrhythmias such as atrial fibrillation or ventricular extra beats require additional calculations. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.	From baseline to Month 48
Other	Change of PR Duration From ECG	PR duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.	From baseline to Month 48
Other	Change of QRS Duration From ECG	QRS duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.	From baseline to Month 48
Other	Change of QT Duration in ECG	QT duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.	From baseline to Month 48
Other	Change in Six-minute Walking Distance (6MWD) Test	6MWD is exercise testing and is one of efficacy evaluation	From baseline to End of study visit, up to 10 years
Other	Change in Pulmonary Vascular Resistance (PVR)	Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. Analyses up to Month 48 due to limited data.	From baseline to Month 45 and Month 48
Other	Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)	NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure	From baseline to End of study visit, up to 10 years
Other	Change in World Health Organization (WHO) Functional Class	WHO classification: I: Participants with PH. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Participants with PH are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Participants with PH are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Participants with PH with inability to carry out any physical activity. They manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. For class change from baseline, minus indicates a participant's functional class decreased compared with baseline (e.g. "-1" indicates a participant changed from class IV to class III, or from class II to class I), plus indicates a participant's functional class increased compared with baseline (e.g. "+1" indicates a participant changed from class I to class II, or from class III to class IV).	From baseline to End of study visit, up to 10 years
Other	Number of Participants With Clinical Worsening	Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH).	From baseline to End of study visit, up to 10 years
Other	Incidence of Clinical Worsening Events Per 100 Person Years	Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH).	From baseline to End of study visit, up to 10 years
Other	Change From Baseline in Borg CR 10 Scale	The Borg CR10 Scale was measured in conjunction with the 6MWD test. The test was explained to the participant before starting the 6MWD test. Participants were asked to rank their exertion at the end of the 6MWD test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").	From baseline to Week 12
Other	Change in Score of EQ-5D Questionnaire	The EQ-5D is a standardized instrument for use as a measure of health outcome. The EQ-5D is a self report questionnaire. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).	From baseline to End of study visit, up to 10 years
Other	Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire	The LPH questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH is a self-report questionnaire and was completed by the participant. The LPH total score can range from 0 (best) to 105 (worst).	From baseline to End of study visit, up to 10 years
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAE)	Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.	From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years
Primary	Number of Participants With Death	Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.	From baseline to end of safety follow-up visit, up to 10 years (1 month more than End of study visit)
Secondary	Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation	Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Secondary	Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation	Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Secondary	Change From Baseline of Hemoglobin in Hematology and Coagulation	Hemoglobin is standard Hematology and coagulation parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Secondary	Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry	Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Secondary	Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry	Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years
Secondary	Change From Baseline of Urate in Clinical Chemistry	Urate is standard clinical chemistry parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.	From baseline to Termination visit, up to 10 years

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