Selexipag for the Treatment of Schistosomiasis-Associated Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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Pulmonary arterial hypertension (PAH) is a severe, progressive and potentially fatal disease that impairs the pulmonary circulation and leads to right ventricular failure. One of the world most prevalent etiologies of PAH is schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH). New drugs have emerged to treat other forms of PAH, but their benefits cannot be automatically translated for Sch-PAH patients, since this etiology was not included in the pivotal PAH trials. One of the most promising therapies for the treatment of PAH to emerge in recent years is selexipag, an oral IP receptor agonist, which acts on the prostacyclin pathway. The present study aims to evaluate the efficacy, safety and tolerability of selexipague for the treatment of schistosomiasis-associated pulmonary arterial hypertension.

Official Title
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Selexipag for the Treatment of Schistosomiasis-Associated Pulmonary Arterial Hypertension

Conditions
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Pulmonary Hypertension, Schistosomiasis

Intervention / Treatment
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* Drug: Selexipag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic Sch-PAH. Sch-PAH diagnosis necessarily include the three criteria below Invasive confirmation of PAH, according to the criteria defined in the Pulmonary Hypertension Sixth World Symposium: mean pulmonary artery pressure higher than 20 mmHg, at rest, and the presence of pulmonary vascular resistance (PVR) equal to or greater than 3 W, and a pulmonary capillary pressure considered normal (equal to or lower than 15 mmHg (1)). At least one epidemiological criteria for chronic schistosomiasis: patient from a highly prevalent region for schistosomiasis or previous history of parasitic treatment for schistosomiasis or the presence of Schistosoma mansoni eggs in the patient's feces Evidence of long-term hepatosplenic involvement by schistosomiasis, via compatible ultrasound findings (peri-portal fibrosis or enlarged left lobe) All patients will necessarily already be receiving at least one specific treatment for PAH, either with phosphodiesterase V inhibitor or with an endothelin receptor antagonist, with a stable dose for at least 12 weeks before inclusion in the study. Exclusion Criteria: Patient without clinical condition to perform the 6-minute walk test Patient with gastro-intestinal bleeding for over 12 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Evaluation of hemodynamics and surrogate markers (clinical variables, BNP levels, six-minute walking test distance, and heat shock protein 70 levels) before and after the introduction of selexipag for the treatment of schistosomiasis-associated pulmonary arterial hypertension patients, that were already receiving at least one therapy for pulmonary arterial hypertension, excluding other drugs from the prostacyclin pathway.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Selexipag<br>Selexipag will be up titrated for a period that will last 12 weeks (Phase 2). The initial dose will be 200 mcg of selexipag every 12 hours, with weekly dose increases of 200 mcg, up to the maximum dose of 1600 mcg every 12 hours or until the classic side effects of the prostacyclin pathway drugs (headache, mandibular pain), among others) arise. The dose will then be reduced by 200 mcg per dose, and this will be the maximum dose considered for that particular patient, maintained in Phase 3 (16 weeks). | Drug: Selexipag<br>* treatment with selexipag<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary vascular resistance |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FC | New York Heart Association Functional Class | 16 weeks | 
| 6MWT | Lenght in the six minute walking distance test | 16 weeks | 
| BNP | Brain Natriuretic Peptide | 16 weeks | 
| HSP 70 | Heat shock protein 70 | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary arterial hypertension, schistosomiasis, selexipag, treatment, efficacy, safety