Long-Term Outcomes of Selexipag in Schistosomiasis-Associated Pulmonary Arterial Hypertension (PROPULSE-Sch)

PROPULSE-Sch: Long-Term Evaluation of Selexipag in Schistosomiasis-Associated Pulmonary Arterial Hypertension Using a Propensity Score-Matched Mirror Cohort

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension (PAH)

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.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Caio Fernandes, Principal Investigator, MD; 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

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adult patients with schistosomiasis-associated pulmonary arterial hypertension (PAH-Sch) followed at a specialized pulmonary hypertension referral center. The population comprises two observational cohorts: patients who initiated oral selexipag as part of routine clinical care and a mirror cohort of clinically similar patients who did not receive selexipag prior to its availability at the center. All patients have confirmed pre-capillary pulmonary arterial hypertension and stable background therapy at the index date. Participants are followed longitudinally using data obtained from routine clinical practice to assess long-term clinical outcomes. No study-mandated interventions are performed.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Selexipag-Treated PAH-Sch Cohort; Adult patients with schistosomiasis-associated pulmonary arterial hypertension who initiated oral selexipag as part of routine clinical care. The index date (T0) is defined as the date of selexipag initiation recorded in the medical record. Patients are followed longitudinally to assess long-term clinical outcomes.
Mirror PAH-Sch Cohort Without Selexipag; Adult patients with schistosomiasis-associated pulmonary arterial hypertension who did not receive selexipag and were followed at the same center prior to its availability. The index date (T0 mirror) is defined as the first visit at which patients met clinical eligibility criteria comparable to those of the treated cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Worsening	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.	From index date (T0) up to 36 months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement Composite Outcome	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.	6, 12, 24, and 36 months after index date
Change in WHO Functional Class	Change in WHO Functional Class	Up to 36 months of follow-up
Change in 6-Minute Walk Distance (6MWD)	Change in 6-Minute Walk Distance (6MWD)	Up to 36 months
Change in BNP or NT-proBNP Levels	Change in BNP or NT-proBNP Levels	Up to 36 months
Hemodynamic Parameters	Change in Mean Pulmonary Arterial Pressure (mPAP)	Up to 36 months of follow-up
Risk Stratification Scores	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.	Up to 36 months of follow-up
Treatment Tolerability	Occurrence of adverse events during follow-up.	Up to 36 months of follow-up
Hemodynamic Parameters	Change in Pulmonary Vascular Resistance (PVR)	Up to 36 months
Hemodynamic Parameters	Change in Pulmonary Capillary Wedge Pressure (PCWP)	Up to 36 months
Hemodynamic Parameters	Change in Cardiac Output or Cardiac Index	Up to 36 months

Collaborators and Investigators

• Sponsor: Caio Júlio César dos Santos Fernandes
• Investigators: Principal Investigator: Caio Fernandes, MD, UNIVERSIDADE SAO PAULO

Publications and helpful links

General Publications

• 1. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. janeiro de 2019;53(1):1801913. 2. Humbert M, Sitbon O, Simonneau G. Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 30 de setembro de 2004;351(14):1425-36. 3. Calderaro D, Alves Junior JL, Fernandes CJCDS, Souza R. Pulmonary Hypertension in General Cardiology Practice. Arq Bras Cardiol [Internet]. 2019 [citado 24 de agosto de 2024]; Disponível em: https://www.scielo.br/scielo.php?pid=S0066-782X2019000900419&script=sci_arttext 4. Yoo HHB. Lesões Plexiformes na Hipertensão Arterial Pulmonar: Estamos Ficando mais Próximos do Manejo com mais Paciência e Rigor? Arq Bras Cardiol. 18 de setembro de 2020;115(3):491-2. 5. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1o de setembro de 1991;115(5):343-9. 6. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1o de fevereiro de 1996;334(5):296-301. 7. Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 17 de novembro de 2005;353(20):2148-57. 8. Rubin LJ, Badesch DB, Barst RJ, Galiè N, Black CM, Keogh A, et al. Bosentan Therapy for Pulmonary Arterial Hypertension. N Engl J Med. 21 de março de 2002;346(12):896-903. 9. Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, et al. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 20 de abril de 2023;388(16):1478-90. 10. Mitchell JA, Ahmetaj-Shala B, Kirkby NS, Wright WR, Mackenzie LS, Reed DM, et al. Role of pr

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Observational Study; Pulmonary Arterial Hypertension; Schistosomiasis; Real-World Evidence; Propensity Score Matching; Long-Term Outcomes; Prostacyclin Pathway
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Respiratory Tract Diseases; Lung Diseases; Parasitic Diseases; Hypertension, Pulmonary; Helminthiasis; Trematode Infections; Pulmonary Arterial Hypertension; Schistosomiasis
• Other Study ID Numbers: SGP 27907

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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