Withdrawal of Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept (WATERLOO) (WATERLOO)
Withdrawal of Background Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept: an Open Label Non-inferiority Trial
Pulmonary arterial hypertension (PAH) is a rare lung disease that leads to elevated blood pressure in the lungs and strain on the right side of the heart. For many years, treatments for PAH have included drugs that target the prostacyclin pathway using intravenous, subcutaneous, oral, and inhaled drugs. These drugs help widen the blood vessels in the lungs so the heart does not have to work as hard. However, these medicines can cause side effects such as jaw pain, flushing, diarrhea, and nausea, and the pump therapy can be very hard to manage day-to-day.
A newer medicine called sotatercept works in a different way. It helps fix some of the root causes of PAH. Early reports suggest that some people do very well on sotatercept and may not need to keep taking their prostacyclin therapy. However, investigators do not yet know if it is safe to stop prostacyclin therapies or how to do so. This study, called WATERLOO, is designed to find out whether slowly stopping prostacyclin therapy while the participant is doing well on sotatercept is safe. Investigators will compare people who stop their prostacyclin therapy to people who keep taking it. This study is being done at PAH expert centres in Canada and Europe.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Canadian VIGOUR Centre Clinical Trial Project Lead
- Номер телефона: 1-800-707-9098
- Электронная почта: waterloo@ualberta.ca
Места учебы
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Alberta
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Edmonton, Alberta, Канада
- University of Alberta Hospital
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Контакт:
- CVC Clinical Trial Project Lead
- Номер телефона: 1-800-707-9098
- Электронная почта: waterloo@ualberta.ca
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
Inclusion Criteria: In order to be eligible for this study, a participant must meet all of the following criteria:
- Adults ≥ 18 years old diagnosed with PAH.
- Treatment with sotatercept for ≥6 months.
- Background therapy with ≥2 PAH vasodilator therapies, one of which is a parenteral prostacyclin or selexipag.
- At low or intermediate-low risk, defined using the 2022 ESC/ERS guidelines 4-strata risk assessment tool (Table 1).
- RHC at screening or historical within 8 weeks of screening, and after at least 6 months of sotatercept treatment, demonstrating a mPAP ≤40 mmHg and PVR ≤5 WU
- The ability to adhere to the study visit schedule and to comprehend and comply with all protocol requirements.
- Ability to provide informed consent.
Exclusion Criteria: A potential participant who meets any of the following criteria will be excluded from participation in this study:
- Known intolerance to sotatercept
- A RHC at screening or historical within 8 weeks of screening and after ≥6 months of sotatercept treatment demonstrating mPAP > 40 mmHg or PVR > 5 WU.
- Hospitalization for worsening PAH or right heart failure within the 3 months prior to screening.
- Active listing for lung or heart/lung transplantation.
- Metastatic cancer or any other condition with a life expectancy < 6 months,
- Female patients who are pregnant or who are of childbearing age and are unwilling to use contraception during the study.
- History of ≥ 3 interruptions or missed doses of sotatercept for any reason within the previous 6 months prior to screening.
- Patients who received any investigational medication within 1 month prior to screening (unless known to be placebo) or who are scheduled to receive another investigational drug during the course of this study.
Учебный план
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 |
|---|---|
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Без вмешательства: Control group / no change to therapy
The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
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Экспериментальный: Prostacyclin pathway therapy withdrawal
Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
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Discontinuation of parenteral prostacyclins analogues or selexipag
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
Временное ограничение: Baseline to 24 weeks
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the change in mean pulmonary arterial pressure (mPAP), measured in mmHg, from baseline to Week 24 by right heart catheterization.
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Baseline to 24 weeks
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Time to First Occurrence of All-Cause Death or Clinical Worsening
Временное ограничение: Baseline to 24 weeks
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Comparison between the prostacyclin pathway therapy withdrawal group and the continuation group in the time to first occurrence of the composite endpoint of all-cause death or clinical worsening.
Clinical worsening is defined as any of the following: hospitalization for worsening PAH, decline in 6-minute walk distance (6MWD) ≥10% from baseline on two consecutive tests at least 4 hours apart accompanied by worsening WHO functional class, or worsening ESC/ERS 4-strata risk status.
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Baseline to 24 weeks
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Change in EmPHasis-10 Score From Baseline to Week 24
Временное ограничение: Baseline to 24 weeks
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the change from baseline to Week 24 Unit of Measure: Score Range: 0-50 Higher scores indicate worse pulmonary hypertension-related quality of life. |
Baseline to 24 weeks
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Change in EQ-5D-5L Index Score From Baseline to Week 24
Временное ограничение: Baseline to Week 24
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the change from baseline to Week 24 in the EQ-5D-5L Index Score. Unit of Measure: Index score Country-specific value set; Higher scores indicate better health status. |
Baseline to Week 24
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Change in EQ Visual Analogue Scale (EQ VAS) Score From Baseline to Week 24
Временное ограничение: Baseline to Week 24
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the change from baseline to Week 24 in the EQ-5D-5L Index Score. Unit of Measure: score Range: 0-100 Higher scores indicate better perceived health. |
Baseline to Week 24
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Change in Living with Medicines Questionnaire Version 3 (LMQ-3) Score From Baseline to Week 24
Временное ограничение: Baseline to Week 24
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the change from baseline to Week 24 in the EQ-5D-5L Index Score. Unit of Measure: Score Range: 41-205 Higher scores indicate a greater medication burden. |
Baseline to Week 24
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Number of Participants Reporting Prostanoid-Associated Side Effects
Временное ограничение: Baseline to 24 weeks
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the number of participants reporting prostanoid-associated side effects, including jaw pain, flushing, nausea, diarrhea, and myalgia.
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Baseline to 24 weeks
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Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Number of Participants Experiencing Adverse Events (AEs)
Временное ограничение: Baseline to 24, 52 and 104 (End of Study) weeks
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the number of participants experiencing one or more adverse events.
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Baseline to 24, 52 and 104 (End of Study) weeks
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Number of Participants Experiencing Serious Adverse Events (SAEs)
Временное ограничение: Baseline to 24, 52 and 104 (End of Study) weeks
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Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the number of participants experiencing one or more serious adverse events.
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Baseline to 24, 52 and 104 (End of Study) weeks
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Participant Enrollment Rate
Временное ограничение: Baseline to 24 weeks
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Number of participants enrolled per site per month during the 24-week recruitment period.
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Baseline to 24 weeks
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Protocol Adherence Rate
Временное ограничение: Baseline to Week 24
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Proportion of participants who complete study procedures according to protocol through Week 24 without major protocol deviations.
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Baseline to Week 24
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Completeness of Secondary and Exploratory Outcome Data
Временное ограничение: Baseline to Week 24
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Proportion of expected secondary and exploratory outcome data points successfully collected through Week 24.
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Baseline to Week 24
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Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: Dr. Jason Weatherald, MD, MSc, FRCPC, University of Alberta
Публикации и полезные ссылки
Общие публикации
- Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Lin J, Johnson-Levonas AO, de Oliveira Pena J, Humbert M, Hoeper MM. Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J. 2023 Sep 21;62(3):2301107. doi: 10.1183/13993003.01107-2023. Print 2023 Sep.
- Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grunig E, Kopec G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6.
- Weatherald J, Iqbal H, Mielniczuk L, Syed AR, Legkaia L, Howard J, Dempsey N, Rader T, Swiston J, Provencher S. Priorities for pulmonary hypertension research: A James Lind Alliance priority setting partnership. J Heart Lung Transplant. 2023 Jan;42(1):1-6. doi: 10.1016/j.healun.2022.09.015. Epub 2022 Oct 3.
- Olsson KM, Fuge J, Park DH, Kamp JC, Hoeper MM. Withdrawal of prostacyclin pathway therapies after initiation of sotatercept treatment in patients with pulmonary arterial hypertension. Eur Respir J. 2025 Jun 5;65(6):2500064. doi: 10.1183/13993003.00064-2025. Print 2025 Jun.
- Preston IR, Badesch D, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Humbert M, McLaughlin VV, Waxman AB, Manimaran S, Mikhailova E, Reddy M, Lau A, de Oliveira Pena J, Souza R. A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA. Eur Respir J. 2025 Jul 24;66(1):2401435. doi: 10.1183/13993003.01435-2024. Print 2025 Jul.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- WATERLOO
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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