Longitudinal Outcomes of Patients With Group 3 Pulmonary Hypertension Treated With Iloprost (AirFly)

AirFly: Longitudinal Outcomes of Patients With Group 3 Pulmonary Hypertension Treated With Iloprost

This observational real-world study aims to evaluate the longitudinal clinical outcomes of adult patients with Group 3 pulmonary hypertension (PH), associated with chronic lung diseases such as interstitial lung disease, who are treated with inhaled iloprost in routine clinical practice.

Treatment options for Group 3 PH remain limited, and the use of pulmonary vasodilators is controversial due to potential worsening of gas exchange. Inhaled iloprost may provide a more selective approach by targeting well-ventilated lung regions. However, real-world data on its use in this population are scarce.

The primary objective of this study is to assess changes in clinical risk status over time using the COMPERA 2.0 four-stratum risk model. Secondary objectives include describing patient characteristics, treatment patterns, and the evolution of functional parameters and biomarkers, as well as documenting relevant clinical events such as hospitalizations, treatment escalation, and discontinuation.

The study will retrospectively analyze data from approximately 50 adult patients with confirmed Group 3 PH who received inhaled iloprost as part of their routine care in a specialized pulmonary hypertension center. No additional patient contact or interventions will occur.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Hypertension Due to Lung Diseases

Detailed Description

Group 3 pulmonary hypertension (PH), associated with chronic lung diseases such as interstitial lung disease, represents a common and clinically challenging PH phenotype, frequently associated with reduced exercise capacity, increased oxygen requirements, and higher mortality. Unlike pulmonary arterial hypertension (Group 1), where targeted therapies have demonstrated clear benefits, treatment options for Group 3 PH remain limited and are primarily focused on management of the underlying lung disease and supportive measures.

The use of systemic pulmonary vasodilators in this population is controversial due to the potential risk of worsening ventilation-perfusion mismatch and hypoxemia. Inhaled prostacyclin analogues may offer a more selective therapeutic approach by preferentially targeting well-ventilated lung regions, potentially mitigating these risks. Inhaled iloprost, approved for pulmonary arterial hypertension, has been used off-label in selected patients with Group 3 PH; however, available evidence is limited and largely derived from small or short-term studies. Data describing real-world patient profiles, treatment patterns, and longitudinal clinical outcomes remain scarce.

Risk stratification has become a key component of disease monitoring in pulmonary hypertension. The COMPERA 2.0 model, which incorporates clinical and non-invasive parameters into a four-stratum risk framework, has demonstrated sensitivity to detect prognostically meaningful changes over time.

This retrospective observational study aims to characterize the clinical evolution of patients with Group 3 PH treated with inhaled iloprost in routine practice. The primary focus is the longitudinal change in risk status according to the COMPERA 2.0 four-stratum model. In addition, the study will explore changes in functional parameters such as WHO functional class and six-minute walk distance, biomarker trends when available, patterns of iloprost use (including monotherapy or combination therapy), and the occurrence of relevant clinical events such as hospitalizations, treatment escalation, and treatment discontinuation.

Data will be obtained from existing medical records of patients followed in a specialized pulmonary hypertension center, without additional patient contact or intervention.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Caio Fernandes, MD, PhD; Phone Number: +551126615034; Email: cjcfernandes@yahoo.com.br

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-900
      • Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo
      • Contact: Caio Fernandes, PhD; Phone Number: 11992149574; Email: cjcfernandes@yahoo.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with pulmonary hypertension due to chronic lung disease and/or hypoxia (group 3 pulmonary hypertension) receiving care at a specialized pulmonary circulation outpatient clinic. The study population includes patients with underlying interstitial lung disease or chronic obstructive pulmonary disease who were treated with inhaled iloprost as part of routine clinical practice. The cohort represents a real-world population followed longitudinally using data available from medical records, without additional study-specific procedures or patient contact.

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of group 3 pulmonary hypertension confirmed by right heart catheterization, defined as mean pulmonary artery pressure >20 mmHg, pulmonary artery wedge pressure ≤15 mmHg, and pulmonary vascular resistance >2 Wood units
• Presence of documented underlying chronic lung disease (e.g., interstitial lung disease confirmed by high-resolution computed tomography with restrictive pattern on pulmonary function testing, or chronic obstructive pulmonary disease)
• Use of inhaled iloprost for a minimum of 3 months, documented in medical records
• Availability of baseline clinical data (at initiation of inhaled iloprost) and at least one follow-up assessment

Exclusion Criteria:

• Pulmonary hypertension from other clinical groups (Groups 1, 2, 4, or 5) as the predominant diagnosis
• Insufficient clinical information in medical records to allow characterization or longitudinal assessment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Group 3 Pulmonary Hypertension Treated With Inhaled Iloprost; Adults (≥18 years) with group 3 pulmonary hypertension (PH due to chronic lung disease and/or hypoxia) followed at a specialized pulmonary circulation outpatient clinic who received inhaled iloprost during routine clinical care. Group 3 PH was confirmed by right heart catheterization according to current hemodynamic criteria and in the presence of documented underlying lung disease (e.g., interstitial lung disease or chronic obstructive pulmonary disease).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Risk Stratification According to the COMPERA 2.0 Four-Stratum Model	Primary outcome is the longitudinal change in clinical risk category assessed using the COMPERA 2.0 four-stratum model (low, intermediate-low, intermediate-high, high risk). Risk status will be determined based on available clinical variables (World Health Organization functional class, 6-minute walk distance, and BNP or NT-proBNP levels, when available). The analysis will evaluate the proportion of patients who demonstrate improvement, stability, or worsening of risk category during follow-up compared with baseline (defined as initiation of inhaled iloprost).	From baseline (initiation of inhaled iloprost) through available follow-up assessments during routine clinical care (follow-up of 3 to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in World Health Organization (WHO) Functional Class	Within-patient longitudinal change in World Health Organization (WHO) functional class during follow-up compared with baseline (defined as initiation of inhaled iloprost). WHO functional class ranges from I (no limitation of physical activity) to IV (inability to carry out any physical activity without symptoms), with higher classes indicating worse functional status.	From baseline (initiation of inhaled iloprost) through available follow-up assessments during routine clinical care (follow-up of 3 to 6 months)
Change in 6-Minute Walk Distance (6MWD)	Within-patient change in 6-minute walk distance (6MWD), measured in meters, comparing baseline (initiation of inhaled iloprost) and follow-up assessments during routine clinical care. Higher values indicate better exercise capacity.	From baseline (initiation of inhaled iloprost) through available follow-up assessments during routine clinical care (follow-up of 3 to 6 months)
Change in BNP or NT-proBNP Levels	Within-patient variation in B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels during follow-up compared with baseline. BNP and NT-proBNP are biomarkers of cardiac stress; higher values indicate worse cardiac strain and prognosis.	From baseline (initiation of inhaled iloprost) through available follow-up assessments during routine clinical care (follow-up of 3 to 6 months)
Clinical Events During Follow-up	Occurrence of clinically relevant events during follow-up, including pulmonary hypertension-related hospitalizations, therapeutic escalation, discontinuation of inhaled iloprost (with reason, when available), and all-cause mortality. These events will be descriptively summarized.	From baseline (initiation of inhaled iloprost) through available follow-up assessments during routine clinical care (follow-up of 3 to 6 months)

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Caio Fernandes, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Observational Study; Interstitial Lung Disease; Group 3 Pulmonary Hypertension; Inhaled Iloprost
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial
• Other Study ID Numbers: SGP 28054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No