Pulmonary Arterial HypertensionREAPPRAISEDNCT07374302
Riociguat in Triple Therapy for Pulmonary Arterial Hypertension in Real-World Practice
An observational study of Pulmonary Arterial Hypertension, run by Caio Júlio César dos Santos Fernandes.
Trial summary
Pulmonary arterial hypertension is a rare and serious disease that can lead to heart failure and early death despite modern treatments. Many patients are treated with a combination of medications targeting different disease pathways, but some continue to have an inadequate response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2026to 31 Dec 2026
- Phase
- Observational
- 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
Study population: The study population includes adult patients with pulmonary arterial hypertension receiving triple therapy who switched from a phosphodiesterase-5 inhibitor to riociguat in routine clinical practice at a specialized referral center. All patients were followed using retrospective data from medical records to assess clinical outcomes, safety, and treatment persistence. No study-related interventions were performed.
Who may be able to join
- Adults aged 18 years or older.
- Confirmed diagnosis of pulmonary arterial hypertension (Group 1).
- Treatment with triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor for at least 12 weeks.
- Switch from a phosphodiesterase-5 inhibitor to riociguat as part of routine clinical care.
- Availability of minimum data to assess the primary outcome at 6 months.
Who cannot join
- Concomitant use of phosphodiesterase-5 inhibitors and riociguat.
- Inability to confirm vital status or hospitalization outcomes within 6 months.
- Participation in an interventional clinical trial that mandated the treatment switch.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: REAPPRAISED: Riociguat in Triple Therapy for Pulmonary Arterial Hypertension - A Single-Center Retrospective Study With Composite Endpoint Evaluation
Pulmonary arterial hypertension is a rare and serious disease that can lead to heart failure and early death despite modern treatments. Many patients are treated with a combination of medications targeting different disease pathways, but some continue to have an inadequate response.
Riociguat is a medication that acts on the nitric oxide pathway and may be beneficial in patients who do not respond well to phosphodiesterase-5 inhibitors. In routine clinical practice, some patients receiving triple therapy switch from a phosphodiesterase-5 inhibitor to riociguat.
The REAPPRAISED study evaluates outcomes in patients with pulmonary arterial hypertension who switched to riociguat while receiving triple therapy. This observational study uses data from routine clinical care and does not involve any experimental treatment. The results may help improve understanding of the effectiveness and safety of this treatment strategy in real-world practice.
Read the detailed description
Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality despite the use of combination therapy. Triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor is commonly used; however, a subset of patients shows an inadequate clinical response.
Riociguat is a soluble guanylate cyclase stimulator that increases cyclic GMP through both nitric oxide-dependent and nitric oxide-independent mechanisms. Switching from a phosphodiesterase-5 inhibitor to riociguat has shown clinical benefit in selected patients, but data in real-world settings and in patients already receiving triple therapy remain limited.
REAPPRAISED is a single-center, retrospective, observational study conducted in a pulmonary hypertension referral center. The study evaluates clinical outcomes following the switch from a phosphodiesterase-5 inhibitor to riociguat in patients with PAH receiving triple therapy. All treatment decisions were made by the treating physicians as part of routine clinical care. No study-mandated interventions or treatment assignments were performed, and data were obtained from medical records.
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, Riociguat, Triple Therapy, Real-World Evidence, PDE5 Inhibitor Switch, Observational Study
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Riociguat Triple Therapy Cohort | Adult patients with pulmonary arterial hypertension receiving triple therapy who switched from a phosphodiesterase-5 inhibitor to riociguat as part of routine clinical care. The index date (T0) is defined as the date of riociguat initiation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Clinical Outcome at 6 Months
Composite clinical outcome assessed at 6 months (24±8 weeks) after the switch to riociguat, defined as achievement of at least two of the following criteria: improvement in six-minute walk distance of at least 10% or 30 meters; World Health Organization functional class I or II; and reduction in BNP levels of at least 30%, in the absence of clinical worsening. Clinical worsening is defined as all-cause mortality, hospitalization due to pulmonary arterial hypertension, or unplanned therapeutic escalation.
Measured: 6 months (24±8 weeks) after switch
Secondary outcomes (5)
Persistence and Time to Discontinuation of Riociguat
reatment persistence at 6 months and time to discontinuation of riociguat for any reason.
Measured: Up to 6 months
Safety Outcomes
Occurrence of adverse events, including symptomatic hypotension, syncope, serious adverse events, and treatment interruptions due to adverse events.
Measured: Up to 6 months
Health Care Utilization
Occurrence of hospitalizations due to pulmonary arterial hypertension and emergency visits in the 6 months before and after the switch to riociguat.
Measured: 6 months before and 6 months after switch
Functional Changes
Changes in functional level before and after the switch to riociguat.
Measured: From baseline to 6 months
Risk Stratification (COMPERA 2.0)
Changes in risk stratification using the COMPERA 2.0 score, when sufficient data are available.
Measured: From baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2026
- Study start1 Mar 2026 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Caio Júlio César dos Santos Fernandes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Caio Júlio César dos Santos Fernandes, University of Sao Paulo General Hospital
- Investigators
- Caio Fernandes, MD, Principal investigator, UNIVERSIDADE SAO PAULO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07374302
- Sponsor's protocol ID
- SGP 27906
- Acronym
- REAPPRAISED
- Status last verified
- Jan 2026
- First submitted
- 12 Jan 2026
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REAPPRAISED: Riociguat in Triple Therapy for Pulmonary Arterial Hypertension - A Single-Center Retrospective Study With Composite Endpoint Evaluation
- ClinicalTrials.gov ID
- NCT07374302
- Acronym / sponsor ID
- REAPPRAISED / SGP 27906
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, Riociguat, Triple Therapy, Real-World Evidence, PDE5 Inhibitor Switch, Observational Study
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Caio Júlio César dos Santos FernandesUniversity, hospital or other
- Study start
- 1 Mar 2026 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 28 Jan 2026 (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.
Pulmonary arterial hypertension is a rare and serious disease that can lead to heart failure and early death despite modern treatments. Many patients are treated with a combination of medications targeting different disease pathways, but some continue to have an inadequate response.
Riociguat is a medication that acts on the nitric oxide pathway and may be beneficial in patients who do not respond well to phosphodiesterase-5 inhibitors. In routine clinical practice, some patients receiving triple therapy switch from a phosphodiesterase-5 inhibitor to riociguat.
The REAPPRAISED study evaluates outcomes in patients with pulmonary arterial hypertension who switched to riociguat while receiving triple therapy. This observational study uses data from routine clinical care and does not involve any experimental treatment. The results may help improve understanding of the effectiveness and safety of this treatment strategy in real-world practice.
Detailed description
Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality despite the use of combination therapy. Triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor is commonly used; however, a subset of patients shows an inadequate clinical response.
Riociguat is a soluble guanylate cyclase stimulator that increases cyclic GMP through both nitric oxide-dependent and nitric oxide-independent mechanisms. Switching from a phosphodiesterase-5 inhibitor to riociguat has shown clinical benefit in selected patients, but data in real-world settings and in patients already receiving triple therapy remain limited.
REAPPRAISED is a single-center, retrospective, observational study conducted in a pulmonary hypertension referral center. The study evaluates clinical outcomes following the switch from a phosphodiesterase-5 inhibitor to riociguat in patients with PAH receiving triple therapy. All treatment decisions were made by the treating physicians as part of routine clinical care. No study-mandated interventions or treatment assignments were performed, and data were obtained from medical records.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Riociguat Triple Therapy Cohort | – | –Adult patients with pulmonary arterial hypertension receiving triple therapy who switched from a phosphodiesterase-5 inhibitor to riociguat as part of routine clinical care. The index date (T0) is defined as the date of riociguat initiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes adult patients with pulmonary arterial hypertension receiving triple therapy who switched from a phosphodiesterase-5 inhibitor to riociguat in routine clinical practice at a specialized referral center. All patients were followed using retrospective data from medical records to assess clinical outcomes, safety, and treatment persistence. No study-related interventions were performed.
Key inclusion criteria (5 listed)
- Adults aged 18 years or older.
- Confirmed diagnosis of pulmonary arterial hypertension (Group 1).
- Treatment with triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor for at least 12 weeks.
- Switch from a phosphodiesterase-5 inhibitor to riociguat as part of routine clinical care.
- Availability of minimum data to assess the primary outcome at 6 months.
Key exclusion criteria (3 listed)
- Concomitant use of phosphodiesterase-5 inhibitors and riociguat.
- Inability to confirm vital status or hospitalization outcomes within 6 months.
- Participation in an interventional clinical trial that mandated the treatment switch.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Composite Clinical Outcome at 6 Months
Time frame: 6 months (24±8 weeks) after switch
Composite clinical outcome assessed at 6 months (24±8 weeks) after the switch to riociguat, defined as achievement of at least two of the following criteria: improvement in six-minute walk distance of at least 10% or 30 meters; World Health Organization functional class I or II; and reduction in BNP levels of at least 30%, in the absence of clinical worsening. Clinical worsening is defined as all-cause mortality, hospitalization due to pulmonary arterial hypertension, or unplanned therapeutic escalation.
5 secondary outcomes
Persistence and Time to Discontinuation of Riociguat
Time frame: Up to 6 months
Safety Outcomes
Time frame: Up to 6 months
Health Care Utilization
Time frame: 6 months before and 6 months after switch
Functional Changes
Time frame: From baseline to 6 months
Risk Stratification (COMPERA 2.0)
Time frame: From baseline to 6 months
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 28 Jan 2026.
- Individual participant dataSharing planned: No
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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.
Caio Fernandes, MD principal investigator
UNIVERSIDADE SAO PAULO
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Arterial Hypertension, run by Caio Júlio César dos Santos Fernandes.
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 3 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: opening soon, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
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.
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 Caio Fernandes, Principal Investigator, MD (+551126615034, cjcfernandes@yahoo.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Clinical Outcome at 6 Months (time frame: 6 months (24±8 weeks) after switch). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jan 2026.