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

NCT07013149 | Recruiting

• 1 other identifier: SGP26691
• Study Type: observational
• Target: 183
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially life-threatening disease characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, and right ventricular dysfunction. The endothelin pathway plays a central role in its pathophysiology and is targeted by endothelin receptor antagonists (ERAs), including ambrisentan and bosentan. Ambrisentan is a selective ETA receptor antagonist, whereas bosentan blocks both ETA and ETB receptors. Although transitions between ERAs occur in clinical practice, evidence regarding the clinical impact of switching from ambrisentan to bosentan remains limited. ACTION is a retrospective, observational, single-center cohort study evaluating adult patients with pulmonary arterial hypertension (World Health Organization Group 1) and/or chronic thromboembolic pulmonary hypertension (World Health Organization Group 4) confirmed by right heart catheterization. Patients who switched from ambrisentan to bosentan because of a national ambrisentan shortage will be compared with clinically similar patients who remained on ambrisentan. Clinical, functional, and laboratory data recorded at baseline and at 3 to 6 months of follow-up will be assessed. The primary outcome is the proportion of patients with worsening risk stratification after switching from ambrisentan to bosentan compared with patients who continued ambrisentan. Risk will be evaluated using the COMPERA 2.0 and REVEAL Lite 2 assessment tools. Secondary outcomes include changes in World Health Organization/New York Heart Association functional class, 6-minute walk distance, BNP levels, individual risk-assessment components, hepatic enzymes, hemoglobin levels, and clinically relevant events such as hospitalization, emergency department visits, initiation of supplemental oxygen, and right heart failure decompensation.

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 participants with worsening clinical risk category from baseline to follow-up, comparing patients who switched from ambrisentan to bosentan with patients who remained on ambrisentan..

  From 3 to 6 months

Secondary Outcomes (6)

• Change in Functional Class

  3 to 6 months

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

  3 to 6 months

• Change in NT-proBNP Levels

  3 to 6 months

• Incidence of Hepatotoxicity

  3 to 6 months

• Change in Hemoglobin Levels

  3 to 6 months

Study Arms (2)

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

Ambrisentan Maintenance Group

This cohort includes adult patients (≥18 years) with a confirmed diagnosis of pulmonary arterial hypertension (PAH) by right heart catheterization who remained on ambrisentan 10 mg once daily and did not undergo a therapeutic switch to bosentan. Clinical, functional, and laboratory data recorded at baseline are compared with data recorded between 3 and 6 months later to evaluate changes in risk stratification scores, functional capacity, laboratory parameters, and clinical events. No investigational drug or additional intervention was administered beyond standard care.

Drug: Maintenance of Ambrisentan Therapy

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

Maintenance of Ambrisentan Therapy DRUG

Continued treatment with ambrisentan 10 mg once daily without transition to bosentan, as part of routine clinical care. Treatment was not assigned by the investigators. Clinical, functional, laboratory, and safety outcomes are assessed over a 3- to 6-month period.

Ambrisentan Maintenance Group

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 or who remained on ambrisentan for at least 6 months without switching. The cohort is representative of a real-world PAH population receiving care at a specialized pulmonary hypertension center. Patients will be retrospectively evaluated 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 for the switch group
• Treatment with ambrisentan for at least 6 months without switching to bosentan for the maintenance group

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: RETROSPECTIVE
• 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: August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)