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

NCT07013149 | Recruiting

• 1 other identifier: SGP26691
• Study Type: observational
• Target: 121
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension (PAH); Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)

Keywords

Pulmonary Arterial Hypertension; PAH; Endothelin Receptor Antagonists; ERA; Ambrisentan; Bosentan; Drug Switching; Risk Stratification

Outcome Measures

Primary Outcomes (1)

• Change in risk category according to used scores

  Proportion of patients who change their clinical risk category (improvement, worsening, or no change) based on scores between baseline (at the time of medication switch) and follow-up (3 to 6 months after the switch from ambrisentan to bosentan).

  3 to 6 months after Endotelin Receptor Antagonist switch

Secondary Outcomes (6)

• Change in Functional Class

  3 to 6 months after Endotelin Receptor Antagonist switch

• Change in 6-Minute Walk Distance (6MWD)

  3 to 6 months after ERA switch

• Change in NT-proBNP Levels

  3 to 6 months after ERA switch

• Incidence of Hepatotoxicity

  3 to 6 months after ERA switch

• Change in Hemoglobin Levels

  3 to 6 months after ERA switch

Study Arms (1)

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.

Other: Switch from Ambrisentan to Bosentan

Interventions

Switch from Ambrisentan to Bosentan OTHER

This intervention refers to a therapeutic switch from ambrisentan (10 mg once daily) to bosentan (125 mg twice daily) in adult patients with pulmonary arterial hypertension (PAH), performed as part of routine clinical care. The switch was not assigned by the investigators but was made based on clinical indications prior to study enrollment. Patients are followed prospectively for up to 6 months to assess changes in risk stratification, functional status, laboratory parameters, and safety outcomes.

Patients who switched from Ambrisentan to Bosentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will include adult patients (≥18 years old) diagnosed with pulmonary arterial hypertension (PAH), confirmed by right heart catheterization, who have undergone a clinically indicated therapeutic switch from ambrisentan to bosentan within the past 6 months. The cohort is representative of a real-world PAH population receiving care at a specialized pulmonary hypertension center. Patients will be prospectively followed for clinical, functional, and laboratory outcomes under routine care conditions.

You may qualify if:

• 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

You may not qualify if:

• History of severe hepatic impairment
• Incomplete clinical or laboratory records that prevent risk score calculation
• Inability to attend clinical follow-up between 3 and 6 months after medication switch

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

InCor - FMUSP

São Paulo, São Paulo, Brazil

RECRUITING

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Caio Fernandes, Principal Investigator

CONTACT

PhD; caio.cesar@hc.fm.usp.br

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: June 10, 2025
• Study Start: August 20, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)