Randomized Study of Triple Therapy vs Sildenafil Dose Optimization in Pulmonary Arterial Hypertension
Recruiting · NCT07713914 · Interventional (participants receive a specific treatment) · Lead sponsor: University of Sao Paulo General Hospital
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterized by increased pressure in the pulmonary arteries, leading to right heart failure and premature death. Although combination therapy has improved outcomes, many patients remain at intermediate or high clinical risk despite treatment. When patients do not reach low-risk status, treatment escalation is recommended. However, different escalation strategies are used in clinical practice, including increasing the dose of existing medications or adding a third drug that targets a different biological pathway. There is limited prospective randomized evidence directly comparing these approaches. The ASCEND-PAH study is a prospective, randomized, open-label clinical trial designed to compare two therapeutic escalation strategies in adults with PAH who remain at intermediate or high risk despite dual therapy with an endothelin receptor antagonist and sildenafil. Participants will be randomized to either: (1) escalation to triple therapy with the addition of a prostacyclin pathway agent, or (2) optimization of dual therapy by increasing the dose of sildenafil. The primary objective is to compare the proportion of patients who improve their risk category according to the COMPERA 2.0 four-stratum risk model within 3 to 6 months after randomization. Secondary outcomes include changes in functional status, exercise capacity, biomarkers, clinical worsening, safety, and treatment persistence
Who can take part
Inclusion criteria
- Age ≥18 years
- Diagnosis of pulmonary arterial hypertension (PAH, Group 1) confirmed according to accepted clinical and hemodynamic criteria
- Stable treatment with an endothelin receptor antagonist in combination with sildenafil prior to randomization
- Classified as intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model
- Clinical indication for therapeutic escalation
- Availability for follow-up assessment between 3 and 6 months after randomization
- Ability to provide written informed consent
Exclusion criteria
- Participation in another interventional clinical trial that mandates treatment modification
- Known contraindication to prostacyclin pathway agents (including iloprost or selexipag)
- Known contraindication to sildenafil dose escalation
- Pregnancy or breastfeeding
- Women of childbearing potential not using effective contraception
- Any clinical condition that, in the investigator's judgment, would interfere with study participation or outcome assessment
Where it is running
1 location listed.
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo - São Paulo, São Paulo, Brazil