ACTION - The Impact of ERA Switching on Risk Stratification in Pulmonary Arterial Hypertension

Status: Recruiting
Location: See location...
Intervention Type: Other
Study Type: Observational
SUMMARY

Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially fatal disease characterized by increased pulmonary vascular resistance and right ventricular dysfunction. Among the four major molecular pathways involved in PAH pathophysiology-nitric oxide, prostacyclin, activin, and endothelin-1 (ET-1)-the endothelin pathway plays a central role. Endothelin-1 acts on ETA and ETB receptors, inducing vasoconstriction and vascular remodeling. Endothelin receptor antagonists (ERAs) are cornerstone therapies in PAH. Ambrisentan is selective for ETA and associated with a lower risk of hepatotoxicity. Bosentan, a dual ERA (ETA/ETB), has well-established efficacy but a higher incidence of liver enzyme elevation, with approximately 9% of patients experiencing hepatic side effects and about 2% discontinuing therapy due to hepatotoxicity. While transitions between ERAs occur in routine clinical practice, data on their clinical impact are scarce. This prospective, observational, single-center cohort study aims to evaluate the effect of switching from ambrisentan to bosentan on risk stratification using the COMPERA 2.0 and REVEAL Lite 2.0 scores at 3-6 months post-switch. Secondary outcomes include variations in functional class (WHO/NYHA), 6-minute walk distance (6MWD), NT-proBNP levels, incidence of adverse events (with a focus on hepatotoxicity), and hematologic parameters such as anemia. The study will enroll adult patients (≥18 years) with confirmed PAH by right heart catheterization who have undergone a documented switch from ambrisentan 10 mg to bosentan 125 mg within the last 6 months. The primary endpoint is the proportion of patients whose risk category changes post-transition according to COMPERA 2.0 and REVEAL Lite 2.0. The results are expected to provide clinically relevant insights into therapeutic decisions involving ERA transitions in PAH management.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Age ≥ 18 years

• Confirmed diagnosis of pulmonary arterial hypertension (PAH) by right heart catheterization

• Documented therapeutic switch from ambrisentan (10 mg once daily) to bosentan (125 mg twice daily) within the previous 6 months

Locations
Other Locations
Brazil
InCor - FMUSP
RECRUITING
São Paulo
Contact Information
Primary
Caio Fernandes, Principal Investigator
caio.cesar@hc.fm.usp.br
PhD
Time Frame
Start Date: 2025-08-20
Estimated Completion Date: 2026-12-01
Participants
Target number of participants: 121
Treatments
Patients who switched from Ambrisentan to Bosentan
This cohort includes adult patients (≥18 years) with a confirmed diagnosis of pulmonary arterial hypertension (PAH) by right heart catheterization who underwent a therapeutic transition from ambrisentan 10 mg once daily to bosentan 125 mg twice daily within the past 6 months. Patients are followed during routine clinical care and assessed between 3 and 6 months after the switch to evaluate changes in risk stratification scores (COMPERA 2.0 and REVEAL Lite 2.0), functional capacity, laboratory parameters, and adverse events. No investigational drug or additional intervention is administered beyond standard care.
Sponsors
Leads: University of Sao Paulo General Hospital

This content was sourced from clinicaltrials.gov

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