Pulmonary Arterial Hypertension (PAH)
Conditions
Keywords
Pulmonary Arterial Hypertension, Schistosomiasis, Prostacyclin Pathway, Real-World Evidence, Propensity Score Matching, Long-Term Outcomes, Observational Study
Brief summary
Schistosomiasis-associated pulmonary arterial hypertension is a serious condition that can lead to shortness of breath, heart failure, frequent hospitalizations, and early death. Although treatments for pulmonary arterial hypertension have improved over time, patients with this specific cause of the disease are often not included in long-term studies. Selexipag is an oral medication used to treat pulmonary arterial hypertension and is part of routine clinical care in Brazil. Its long-term effects in patients with schistosomiasis-associated pulmonary arterial hypertension are not well understood. The PROPULSE-Sch study aims to evaluate long-term clinical outcomes in patients with schistosomiasis-associated pulmonary arterial hypertension who received selexipag, compared with similar patients who did not receive this medication before it became available at the study center. This is an observational study using data from routine medical care. All treatments are prescribed by the treating physicians, and participation in the study does not change patient care. The results may help improve understanding of long-term outcomes and support treatment decisions in this population.
Detailed description
Schistosomiasis-associated pulmonary arterial hypertension (PAH-Sch) is a prevalent cause of pulmonary arterial hypertension in endemic regions and is associated with significant morbidity and premature mortality. Despite advances in targeted therapies for pulmonary arterial hypertension, patients with PAH-Sch remain underrepresented in long-term studies, particularly in real-world clinical settings. Selexipag, an oral selective prostacyclin IP receptor agonist, has demonstrated clinical and hemodynamic benefits in pulmonary arterial hypertension. Following its incorporation into routine clinical practice in Brazil, selexipag has been increasingly used in eligible patients with PAH-Sch. However, evidence regarding its long-term outcomes in this specific population is limited. PROPULSE-Sch is a single-center, observational, longitudinal study with an ambispective design, combining retrospective data and prospective follow-up. The study evaluates long-term clinical outcomes associated with exposure to selexipag in patients with PAH-Sch, compared with a mirror cohort of clinically similar patients who did not receive selexipag prior to its availability at the center. To reduce confounding and indication bias inherent to observational comparisons, analyses are conducted using propensity score matching. All treatment decisions, including initiation and intensification of therapy, are made exclusively by the treating physicians as part of routine clinical care. The study does not mandate any intervention, treatment assignment, or protocol-driven management. Data are obtained from medical records and standard follow-up visits. By using real-world data and robust observational methods, this study aims to contribute clinically relevant evidence on long-term outcomes in schistosomiasis-associated pulmonary arterial hypertension.
Interventions
None listed
Sponsors
Caio Júlio César dos Santos Fernandes
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults aged 18 years or older. * Confirmed diagnosis of pulmonary arterial hypertension associated with schistosomiasis (PAH-Sch). * Diagnosis of pre-capillary pulmonary arterial hypertension confirmed by right heart catheterization, performed at any time prior to the index date (T0), as documented in the medical record. * Evidence of schistosomiasis infection, including epidemiological history and ultrasonographic findings compatible with hepatosplenic schistosomiasis. * Previous antiparasitic treatment for schistosomiasis. * Clinical stability at the index date, defined as absence of progressive right heart failure or clinical worsening within the previous 12 weeks. * World Health Organization (WHO) functional class I-III at the index date. * Stable background pulmonary arterial hypertension-specific therapy with a phosphodiesterase-5 inhibitor and/or endothelin receptor antagonist for at least 12 weeks prior to the index date. * For the treated cohort: initiation of oral selexipag as part of routine clinical care. * For the mirror cohort: eligibility for therapeutic escalation at the index date without exposure to selexipag.
Exclusion criteria
* World Health Organization (WHO) functional class IV at the index date. * Progressive right heart failure or clinical deterioration within the 12 weeks prior to the index date. * Documented formal contraindication to selexipag in the medical record. * Insufficient baseline data at the index date to allow clinical characterization or inclusion in propensity score analyses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Worsening | From index date (T0) up to 36 months of follow-up | Time from the index date (T0) to the first occurrence of clinical worsening, defined as any of the following events: all-cause mortality; lung transplantation; non-elective hospitalization due to pulmonary arterial hypertension or right heart failure; therapeutic escalation defined as initiation of parenteral prostacyclin or addition of a new class of pulmonary arterial hypertension-specific therapy; or sustained worsening of World Health Organization functional class confirmed in two consecutive assessments at least 12 weeks apart and accompanied by objective evidence of disease progression, including a ≥15% decrease in six-minute walk distance and/or a ≥30% increase in BNP or NT-proBNP compared with baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement Composite Outcome | 6, 12, 24, and 36 months after index date | Composite clinical improvement defined as improvement in at least two of the following criteria compared with baseline, without occurrence of clinical worsening: increase of at least 10% or 30 meters in six-minute walk distance; improvement to World Health Organization functional class I or II; or reduction of at least 30% in BNP or NT-proBNP levels. |
| Change in WHO Functional Class | Up to 36 months of follow-up | Change in WHO Functional Class |
| Change in 6-Minute Walk Distance (6MWD) | Up to 36 months | Change in 6-Minute Walk Distance (6MWD) |
| Change in BNP or NT-proBNP Levels | Up to 36 months | Change in BNP or NT-proBNP Levels |
| Hemodynamic Parameters | Up to 36 months of follow-up | Change in Mean Pulmonary Arterial Pressure (mPAP) |
| Risk Stratification Scores | Up to 36 months of follow-up | Changes in pulmonary arterial hypertension risk stratification assessed using the COMPERA 2.0 risk score (four risk strata: low, intermediate-low, intermediate-high, and high risk), evaluated during follow-up when sufficient clinical, functional, and laboratory data are available. |
| Treatment Tolerability | Up to 36 months of follow-up | Occurrence of adverse events during follow-up. |
Countries
Brazil
Contacts
CONTACTCaio Fernandes, Principal Investigator, MD
PRINCIPAL_INVESTIGATORCaio Fernandes, MD
UNIVERSIDADE SAO PAULO
Outcome results
None listed