Randomized Study of Triple Therapy vs Sildenafil Dose Optimization in Pulmonary Arterial Hypertension

Recruiting now · Phase 4

Conditions studied: Pulmonary Arterial Hypertension (PAH)

In brief

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

Key facts

Study ID: NCT07713914
Run by: University of Sao Paulo General Hospital
People needed: 196
Starts: 2026-07-22
Expected to finish: 2028-12-31
Last updated by the study team: 2026-07-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo — São Paulo, São Paulo, Brazil (enrolling)

Full record on ClinicalTrials.gov

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