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Randomized Study of Triple Therapy vs Sildenafil Dose Optimization in Pulmonary Arterial Hypertension (ASCEND-PAH)

28 июля 2026 г. обновлено: Caio Júlio César dos Santos Fernandes, University of Sao Paulo General Hospital

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

Обзор исследования

Статус

Рекрутинг

Условия

Вмешательство/лечение

Подробное описание

This is a prospective, randomized, open-label, parallel-group clinical trial designed to evaluate therapeutic escalation strategies in adults with pulmonary arterial hypertension (PAH, Group 1) who remain at intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model despite stable dual therapy.

Eligible participants must be receiving an endothelin receptor antagonist in combination with sildenafil and have a clinical indication for treatment escalation. After confirmation of eligibility and baseline assessments, participants will be randomized in a 1:1 ratio to one of two strategies:

Escalation to triple therapy through addition of a prostacyclin pathway agent (inhaled iloprost or selexipag), according to clinical judgment and availability.

Optimization of dual therapy by increasing the dose of sildenafil according to clinical practice.

Baseline assessments may include WHO functional class, 6-minute walk distance, and BNP or NT-proBNP levels obtained within 90 days prior to randomization. Follow-up evaluation will occur between 3 and 6 months after randomization, with the primary analysis based on the assessment closest to 6 months within that window.

The primary endpoint is the proportion of patients who achieve improvement in risk stratification, defined as a decrease of at least one risk category according to the COMPERA 2.0 four-stratum model. Secondary endpoints include composite clinical improvement and worsening, change in individual clinical parameters, time to clinical worsening, safety outcomes, need for additional therapeutic escalation, and treatment persistence.

The study is powered to detect a clinically meaningful absolute difference of 20 percentage points in risk improvement between groups, with planned enrollment of approximately 196 participants to account for potential losses to follow-up

Тип исследования

Интервенционный

Регистрация (Оцененный)

196

Фаза

  • Фаза 4

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

  • Имя: Caio Fernandes, MD, PhD
  • Номер телефона: +551126615034
  • Электронная почта: cjcfernandes@yahoo.com.br

Места учебы

  • Бразилия
    • São Paulo
      • São Paulo, São Paulo, Бразилия, 04551-060
        • Рекрутинг
        • Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo
        • Контакт:
          • Caio Fernandes, Principal Investigator
          • Номер телефона: 1126615034
          • Электронная почта: cjcfernandes@yahoo.com.br

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

  • Взрослый
  • Пожилой взрослый

Принимает здоровых добровольцев

Нет

Описание

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

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Активный компаратор: Sildenafil Dose Optimization
Participants will continue dual therapy with an endothelin receptor antagonist and sildenafil, with optimization of sildenafil dose according to clinical practice. No additional pulmonary arterial hypertension pathway agent will be added at randomization. Treatment adjustments after randomization will be recorded if clinically required.
Лекарство: Sildenafil Dose Optimization
Optimization of sildenafil dose within approved dosing ranges as part of dual therapy with an endothelin receptor antagonist. Dose adjustments will be performed according to clinical practice to achieve maximal tolerated and guideline-recommended dosing without addition of a new PAH pathway agent at randomization.
Другие имена:
  • Силденафил
Экспериментальный: Triple Therapy Escalation (Inhaled Iloprost or Selexipag)
Participants will receive escalation to triple therapy through addition of a prostacyclin pathway agent (inhaled iloprost or selexipag) to ongoing dual therapy with an endothelin receptor antagonist and sildenafil. The specific prostacyclin pathway agent will be selected according to clinical judgment and availability. Participants will remain on triple therapy during follow-up unless modification is clinically indicated.
Лекарство: Prostacyclin Pathway Agent
Addition of a prostacyclin pathway agent (inhaled iloprost or oral selexipag) to ongoing dual therapy with an endothelin receptor antagonist and sildenafil as part of therapeutic escalation to triple therapy. The specific agent will be selected according to clinical judgment and availability. Dosing will follow approved labeling and routine clinical practice.
Другие имена:
  • Селексипаг
  • Илопрост

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Improvement in Risk Stratification According to the COMPERA 2.0 Four-Stratum Model
Временное ограничение: Between 3 and 6 months after randomization (assessment closest to 6 months within the predefined window)
Proportion of participants who achieve improvement in clinical risk category between baseline and follow-up, defined as a decrease of at least one risk category according to the COMPERA 2.0 four-stratum model (low, intermediate-low, intermediate-high, high risk). Risk status is determined using World Health Organization functional class, 6-minute walk distance, and BNP or NT-proBNP levels, when available.
Between 3 and 6 months after randomization (assessment closest to 6 months within the predefined window)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Composite Clinical Improvement at 3-6 Months
Временное ограничение: Between 3 and 6 months after randomization
Proportion of participants who achieve composite clinical improvement between baseline and follow-up (3-6 months), defined as improvement in at least two of the following without worsening in any: (1) improvement of ≥1 WHO functional class; (2) increase of ≥30 meters in 6-minute walk distance; (3) reduction of ≥30% in BNP or NT-proBNP levels.
Between 3 and 6 months after randomization
Composite Clinical Worsening
Временное ограничение: From randomization through 6 months of follow-up
Occurrence of clinical worsening defined as any of the following during follow-up: worsening of ≥1 WHO functional class; decrease of ≥30 meters in 6-minute walk distance; increase of ≥30% in BNP or NT-proBNP; need for additional therapeutic escalation; hospitalization related to pulmonary arterial hypertension; or death from any cause.
From randomization through 6 months of follow-up
Change in WHO Functional Class
Временное ограничение: Between 3 and 6 months after randomization
Change in World Health Organization (WHO) functional class between baseline and follow-up. WHO functional class ranges from I (least severe) to IV (most severe), with higher classes indicating worse functional limitation.
Between 3 and 6 months after randomization
Change in 6-Minute Walk Distance (6MWD)
Временное ограничение: Between 3 and 6 months after randomization
Absolute change in 6-minute walk distance (meters) between baseline and follow-up assessment.
Between 3 and 6 months after randomization
Change in BNP or NT-proBNP Levels
Временное ограничение: Between 3 and 6 months after randomization
Percent change in BNP or NT-proBNP levels between baseline and follow-up. Higher values indicate greater cardiac strain and worse prognosis.
Between 3 and 6 months after randomization
Time to Clinical Worsening
Временное ограничение: From randomization through 6 months of follow-up
Time from randomization to first occurrence of clinical worsening event as defined in the composite clinical worsening outcome.
From randomization through 6 months of follow-up
Treatment Persistence
Временное ограничение: From randomization through 6 months of follow-up
Proportion of participants who remain on their initially assigned therapeutic strategy without permanent discontinuation by the follow-up visit.
From randomization through 6 months of follow-up
Safety and Adverse Events
Временное ограничение: From randomization through 6 months
Incidence, type, and severity of adverse events and serious adverse events occurring during the study period.
From randomization through 6 months

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

University of Sao Paulo General Hospital

Следователи

  • Главный следователь: Caio Fernandes, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

22 июля 2026 г.

Первичное завершение (Оцененный)

1 июля 2028 г.

Завершение исследования (Оцененный)

31 декабря 2028 г.

Даты регистрации исследования

Первый отправленный

14 июля 2026 г.

Впервые представлено, что соответствует критериям контроля качества

14 июля 2026 г.

Первый опубликованный (Действительный)

20 июля 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

30 июля 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

28 июля 2026 г.

Последняя проверка

1 июля 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • CAAE: 97708926.6.0000.0068

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕ РЕШЕНО

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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