Chronic Thromboembolic Pulmonary HypertensionPhase 4S2RNCT06715280
Switching of Sildenafil to Riociguat in CTEPH Patients
A Phase 4 study testing Riociguat (Adempas) in people with Chronic Thromboembolic Pulmonary Hypertension, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
This study was designed to investigate the safety and efficacy of replacing phosphodiesterase 5 inhibitors (PDE5i) with riociguat in patients with Chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone pulmonary angioplasty (BPA) and remains symptomatic despite treatments with PDE5i. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension
- What is being tested?
- Riociguat (Adempas)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteHong Kong
- Study dates
- 25 Jul 2024to 22 Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with established diagnosis of CTEPH who are symptomatic after Balloon pulmonary angioplasty (BPA)
- Patients who are on stable maximally tolerated dose of sildenafil for at least 6 weeks as monotherapy, or in combination with other pulmonary hypertension specific therapies
- WHO functional class III at screening
- Stable dose of diuretics (if used) for at least 30 days at screening
- No recent hospitalisation due to pulmonary hypertension or heart failure for at least 30 days
Who cannot join
- Previous treatment with riociguat other sGCs, or documented severe drug reaction or intolerance to sGCs
- Use of nitrates or nitric oxide donors (eg, nitroglycerin, amyl nitrite, isosorbide dinitrate etc) by any administration routes within 30 days of screening
- Pregnant women or breast-feeding women, or women with childbearing potential not using of combination of two effective contraception methods throughout study
- Renal impairment with glomerular filtration rate <15mL /min
- Child-Pugh C hepatic impairment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong
Daniel Xu Nurse, +85235051518, danielxu@cuhk.edu.hk
About this study
Official title: Switching Sildenafil to Riociguat in Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty
This study was designed to investigate the safety and efficacy of replacing phosphodiesterase 5 inhibitors (PDE5i) with riociguat in patients with Chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone pulmonary angioplasty (BPA) and remains symptomatic despite treatments with PDE5i.
Read the detailed description
Chronic thromboembolic pulmonary hypertension (CTEPH) results from the obstruction of the pulmonary arteries by organised fibrotic thrombi and the associated microvasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. CTEPH is associated with significant mortality and morbidity, so prompt initiation of treatments are necessary to improve the prognosis.
For those with accessible pulmonary arteries occlusions, surgical pulmonary endarterectomy (PEA) is the treatment of choice. Nevertheless, about 40% of CTEPH patients are not considered to be operable due to occlusion of distal pulmonary vessels. For patients with inoperative CTEPH, current treatment options include balloon pulmonary angioplasty (BPA) and medical therapies.
Several medical therapies that target microvascular components of CTEPH, such as phosphodiesterase type 5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), have been used off-label, as the efficacy of those medications in inoperable CTEPH has not been proven in randomised controlled trials or registry data. The CHEST-1 randomised controlled trial demonstrated that the soluble guanylate cyclase stimulator (sGCs), riociguat, significantly reduced pulmonary vascular resistance and improved exercise capacity in patients with inoperative CTEPH or persistent or recurrent pulmonary hypertension after PEA. Based on the finding of this study, riociguat has been approved for treatment for symptomatic inoperable patients with CTEPH.
Both PDE5i and sGCs act via the same nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, but these two classes of medications target different molecular targets in the same pathway. PDE5i inhibits the degradation of cGMP, so its efficacy is dependent on a functioning NO-sGC-cGMP axis and the presence of intracellular cGMP. In contrast, riociguat stimulates sGC directly, thus it increases intracellular cGMP level regardless the presence of NO. Therefore, based on this biological rationale, it is postulated that riociguat may be more effective in increasing intracellular cGMP compared to PDE5i. Currently there is no head-to-head trials comparing the efficacy of PDE5i and riociguat in treating pulmonary hypertension. Nevertheless, 2 clinical trials have demonstrated improvement in the clinical and biochemical parameters after switching from PDE5i to sGCs in selected patients with pulmonary arterial hypertension (PAH) with insufficient response to PDE5i. It is currently unknown whether this switching will also apply to patients with CTEPH as those 2 clinical trials do not include patients with CTEPH.
In addition to medical therapies, BPA, an endovascular procedure to dilate the occlusions and stricture in segmental or subsegmental pulmonary arteries, has emerged as a treatment for patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after PEA. Two randomised controlled trials comparing BPA and riociguat have demonstrated that BPA was associated with a greater improvement in mean pulmonary artery pressure and reduction in pulmonary vascular resistance in inoperable CTEPH patients.
Currently, the data of safety and efficacy of switching PDE5i to sGCs after BPA is lacking. Therefore, this study was designed to investigate the safety and efficacy of replacing PDE5i with riociguat in patients with CTEPH who have undergone BPA and remains symptomatic despite treatments with PDE5i.
- Being tested
- Riociguat (Adempas)
- Keywords
- CTEPH, BPA, Riociguat, Sildenafil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat (Adempas)Drug
Oral riociguat administered according to established dose-adjustment scheme. Riociguat will be administered starting at at 1mg three times per day. If patient systolic blood pressure maintains at 95mmHg or higher, the dose will be increased 0.5mg every 2 weeks up to a maximum dose 2.5mg three times per day over 8-week period
| Study group | Role | What they receive |
|---|---|---|
| Patients with Chronic Thromboembolic Pulmonary Hypertension | Other | Patients with Chronic Thromboembolic Pulmonary Hypertension under Sildenafil treatment Receives: Drug: Riociguat (Adempas) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean pulmonary artery pressure (mPAP)
Change in mean pulmonary artery pressure (mPAP) measured in right heart catheterization at baseline and at week 26. Pulmonary hypertension (PH) is defined as pulmonary artery pressure (PAP) ≥ 25 mmHg. And the normal resting PAP is 8-20 mmHg.
Measured: 26 weeks
Change in pulmonary vascular resistance (PVR)
Change in pulmonary vascular resistance (PVR) measured in right heart catheterization at baseline and at week 26. Pulmonary vascular resistance (PVR) is similar to systemic vascular resistance (SVR) except it refers to the arteries that supply blood to the lungs.
Measured: 26 weeks
Secondary outcomes (10)
Change in cardiac output (CO)
Change in cardiac output (CO) measured in right heart catheterization. Cardiac output (CO) is the product of the heart rate (HR), i.e. the number of heartbeats per minute (bpm), and the stroke volume (SV), which is the volume of blood pumped from the left ventricle per beat.
Measured: 26 weeks
Change in cardiac index (CI)
Change in cardiac index (CI) measured in right heart catheterization. The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). It is crucial in assessing patients with heart failure and other cardiovascular conditions
Measured: 26 weeks
Change in pulmonary artery wedge pressure (PAWP)
Change in pulmonary artery wedge pressure (PAWP) measured in right heart catheterization. It is the pressure measured by wedging a pulmonary artery catheter with an inflated balloon into a small pulmonary arterial branch
Measured: 26 weeks
Change in The World Health Organization (WHO) functional class
Change in WHO functional class describes how severe a patient's pulmonary hypertension (PH) symptoms. There are four different classes - I is the mildest and IV the most severe form of PH.
Measured: 26 weeks
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) level
Change in NT-proBNP level which is a protein that's an "ingredient" for making the BNP hormone. Like BNP, your heart makes larger amounts of NT-proBNP when it has to work harder to pump blood.
Measured: 26 weeks
Change in walk distance by 6-minutes walk test
Change in walk distance by 6-minutes walk test which is a sub-maximal exercise test used to assess aerobic capacity and endurance.
Measured: 26 weeks
Change in Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL) score
Change in Pulmonary Embolism Quality of Life Questionnaire score which is a reliable instrument to specifically assess Quality of Life following Pulmonary Embolism, which is helpful in the identification of patients with decreased Quality of Life following acute Pulmonary Embolism.
Measured: 26 weeks
Change in REVEAL lite 2 risk score
Change in REVEAL lite 2 risk score which is quickly calculate patient's risk score and to help determine whether treatment escalation may be needed
Measured: 26 weeks
Change in tricuspid regurgitation pressure gradient (TRPG)
Change in tricuspid regurgitation pressure gradient (TRPG) which reflects the difference in pressure between the right ventricle and right atrium on echocardiogram
Measured: 26 weeks
Change in tricuspid annular plane systolic excursion (TAPSE)
Change in tricuspid annular plane systolic excursion (TAPSE) which a parameter of global RV function which describes apex-to-base shortening on echocardiogram
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start25 Jul 2024
- Primary completion22 Jul 2026 (estimated)
- Study completion22 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, open-labelled, single-arm study
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, GuangMing Tan, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715280
- Sponsor's protocol ID
- 2023.577
- Acronym
- S2R
- Status last verified
- May 2025
- First submitted
- 26 Nov 2024
- Last updated
- 29 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kam THH, Kam KKH, Wong MKL, Yan BPY, Tan G. Haemodynamic and clinical impacts of switching phosphodiesterase-5 inhibitors to riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after balloon pulmonary angioplasty (BPA) - a prospective cohort study. BMC Pulm Med. 2026 Jan 3;26(1):42. doi: 10.1186/s12890-025-04069-y.
PubMed 41484960
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching Sildenafil to Riociguat in Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty
- ClinicalTrials.gov ID
- NCT06715280
- Acronym / sponsor ID
- S2R / 2023.577
- Keywords
- CTEPH, BPA, Riociguat, Sildenafil
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 25 Jul 2024 (actual)
- Primary completion
- 22 Jul 2026 (estimated)
- Study completion
- 22 Jan 2027 (estimated)
- First posted
- 4 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was designed to investigate the safety and efficacy of replacing phosphodiesterase 5 inhibitors (PDE5i) with riociguat in patients with Chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone pulmonary angioplasty (BPA) and remains symptomatic despite treatments with PDE5i.
Detailed description
Chronic thromboembolic pulmonary hypertension (CTEPH) results from the obstruction of the pulmonary arteries by organised fibrotic thrombi and the associated microvasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. CTEPH is associated with significant mortality and morbidity, so prompt initiation of treatments are necessary to improve the prognosis.
For those with accessible pulmonary arteries occlusions, surgical pulmonary endarterectomy (PEA) is the treatment of choice. Nevertheless, about 40% of CTEPH patients are not considered to be operable due to occlusion of distal pulmonary vessels. For patients with inoperative CTEPH, current treatment options include balloon pulmonary angioplasty (BPA) and medical therapies.
Several medical therapies that target microvascular components of CTEPH, such as phosphodiesterase type 5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), have been used off-label, as the efficacy of those medications in inoperable CTEPH has not been proven in randomised controlled trials or registry data. The CHEST-1 randomised controlled trial demonstrated that the soluble guanylate cyclase stimulator (sGCs), riociguat, significantly reduced pulmonary vascular resistance and improved exercise capacity in patients with inoperative CTEPH or persistent or recurrent pulmonary hypertension after PEA. Based on the finding of this study, riociguat has been approved for treatment for symptomatic inoperable patients with CTEPH.
Both PDE5i and sGCs act via the same nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, but these two classes of medications target different molecular targets in the same pathway. PDE5i inhibits the degradation of cGMP, so its efficacy is dependent on a functioning NO-sGC-cGMP axis and the presence of intracellular cGMP. In contrast, riociguat stimulates sGC directly, thus it increases intracellular cGMP level regardless the presence of NO. Therefore, based on this biological rationale, it is postulated that riociguat may be more effective in increasing intracellular cGMP compared to PDE5i. Currently there is no head-to-head trials comparing the efficacy of PDE5i and riociguat in treating pulmonary hypertension. Nevertheless, 2 clinical trials have demonstrated improvement in the clinical and biochemical parameters after switching from PDE5i to sGCs in selected patients with pulmonary arterial hypertension (PAH) with insufficient response to PDE5i. It is currently unknown whether this switching will also apply to patients with CTEPH as those 2 clinical trials do not include patients with CTEPH.
In addition to medical therapies, BPA, an endovascular procedure to dilate the occlusions and stricture in segmental or subsegmental pulmonary arteries, has emerged as a treatment for patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after PEA. Two randomised controlled trials comparing BPA and riociguat have demonstrated that BPA was associated with a greater improvement in mean pulmonary artery pressure and reduction in pulmonary vascular resistance in inoperable CTEPH patients.
Currently, the data of safety and efficacy of switching PDE5i to sGCs after BPA is lacking. Therefore, this study was designed to investigate the safety and efficacy of replacing PDE5i with riociguat in patients with CTEPH who have undergone BPA and remains symptomatic despite treatments with PDE5i.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, open-labelled, single-arm study
| Arm | Type | Receives |
|---|---|---|
| Patients with Chronic Thromboembolic Pulmonary Hypertension | Other | Drug: Riociguat (Adempas)Patients with Chronic Thromboembolic Pulmonary Hypertension under Sildenafil treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with established diagnosis of CTEPH who are symptomatic after Balloon pulmonary angioplasty (BPA)
- Patients who are on stable maximally tolerated dose of sildenafil for at least 6 weeks as monotherapy, or in combination with other pulmonary hypertension specific therapies
- WHO functional class III at screening
- Stable dose of diuretics (if used) for at least 30 days at screening
- No recent hospitalisation due to pulmonary hypertension or heart failure for at least 30 days
Key exclusion criteria (5 listed)
- Previous treatment with riociguat other sGCs, or documented severe drug reaction or intolerance to sGCs
- Use of nitrates or nitric oxide donors (eg, nitroglycerin, amyl nitrite, isosorbide dinitrate etc) by any administration routes within 30 days of screening
- Pregnant women or breast-feeding women, or women with childbearing potential not using of combination of two effective contraception methods throughout study
- Renal impairment with glomerular filtration rate <15mL /min
- Child-Pugh C hepatic impairment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riociguat (Adempas)Oral riociguat administered according to established dose-adjustment scheme. Riociguat will be administered starting at at 1mg three times per day. If patient systolic blood pressure maintains at 95mmHg or higher, the dose will be increased 0.5mg every 2 weeks up to a maximum dose 2.5mg three times per day over 8-week period | Drug | Patients with Chronic Thromboembolic Pulmonary Hypertension |
Primary outcome
Change in mean pulmonary artery pressure (mPAP)
Time frame: 26 weeks
Change in mean pulmonary artery pressure (mPAP) measured in right heart catheterization at baseline and at week 26. Pulmonary hypertension (PH) is defined as pulmonary artery pressure (PAP) ≥ 25 mmHg. And the normal resting PAP is 8-20 mmHg.
Change in pulmonary vascular resistance (PVR)
Time frame: 26 weeks
Change in pulmonary vascular resistance (PVR) measured in right heart catheterization at baseline and at week 26. Pulmonary vascular resistance (PVR) is similar to systemic vascular resistance (SVR) except it refers to the arteries that supply blood to the lungs.
10 secondary outcomes
Change in cardiac output (CO)
Time frame: 26 weeks
Change in cardiac index (CI)
Time frame: 26 weeks
Change in pulmonary artery wedge pressure (PAWP)
Time frame: 26 weeks
Change in The World Health Organization (WHO) functional class
Time frame: 26 weeks
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) level
Time frame: 26 weeks
Change in walk distance by 6-minutes walk test
Time frame: 26 weeks
Change in Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL) score
Time frame: 26 weeks
Change in REVEAL lite 2 risk score
Time frame: 26 weeks
Change in tricuspid regurgitation pressure gradient (TRPG)
Time frame: 26 weeks
Change in tricuspid annular plane systolic excursion (TAPSE)
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2025.
- Derived from this study: PubMed 41484960Kam THH, Kam KKH, Wong MKL, Yan BPY, Tan G. Haemodynamic and clinical impacts of switching phosphodiesterase-5 inhibitors to riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after balloon pulmonary angioplasty (BPA) - a prospective cohort study. BMC Pulm Med. 2026 Jan 3;26(1):42. doi: 10.1186/s12890-025-04069-y.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Riociguat (Adempas) in people with Chronic Thromboembolic Pulmonary Hypertension, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel Xu Nurse (+85235051518, danielxu@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mean pulmonary artery pressure (mPAP) (time frame: 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06715280, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025.