Adding a third drug versus a higher sildenafil dose in pulmonary arterial hypertension
Compares two ways to step up treatment in adults with pulmonary arterial hypertension.
Plain-language title generated from the registry record
Registry title: Randomized Study of Triple Therapy vs Sildenafil Dose Optimization in Pulmonary Arterial Hypertension
Key facts
- Where
- São Paulo, BrazilSee the site
- Phase
- Phase 4
Where in Brazil
- Instituto do Coração InCor, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloSão Paulo, BrazilTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- University of Sao Paulo General Hospital
- Trial code
- NCT07713914
- Record updated
- 30 July 2026
- Original description
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.Read full original descriptionShow less
A Prospective, Randomized, Open-Label Study Comparing Triple Therapy Versus Sildenafil Dose Optimization in Patients With Pulmonary Arterial Hypertension Using COMPERA 2.0 Risk Stratification as the Primary Outcome
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
Inclusion: 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: Any clinical condition that, in the investigator's judgment, would interfere with study participation or outcome assessment; 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.