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.
調査の概要
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Canadian VIGOUR Centre Clinical Trial Project Lead
- 電話番号：1-800-707-9098
- メール：waterloo@ualberta.ca
研究場所
-
-
Alberta
-
Edmonton、Alberta、カナダ
- University of Alberta Hospital
-
コンタクト：
- CVC Clinical Trial Project Lead
- 電話番号：1-800-707-9098
- メール：waterloo@ualberta.ca
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
介入なし：Control group / no change to therapy
The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
|
|
|
実験的：Prostacyclin pathway therapy withdrawal
Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
|
Discontinuation of parenteral prostacyclins analogues or selexipag
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
時間枠：Baseline to 24 weeks
|
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.
|
Baseline to 24 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time to First Occurrence of All-Cause Death or Clinical Worsening
時間枠：Baseline to 24 weeks
|
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.
|
Baseline to 24 weeks
|
|
Change in EmPHasis-10 Score From Baseline to Week 24
時間枠：Baseline to 24 weeks
|
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
|
|
Change in EQ-5D-5L Index Score From Baseline to Week 24
時間枠：Baseline to Week 24
|
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
|
|
Change in EQ Visual Analogue Scale (EQ VAS) Score From Baseline to Week 24
時間枠：Baseline to Week 24
|
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
|
|
Change in Living with Medicines Questionnaire Version 3 (LMQ-3) Score From Baseline to Week 24
時間枠：Baseline to Week 24
|
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
|
|
Number of Participants Reporting Prostanoid-Associated Side Effects
時間枠：Baseline to 24 weeks
|
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.
|
Baseline to 24 weeks
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants Experiencing Adverse Events (AEs)
時間枠：Baseline to 24, 52 and 104 (End of Study) weeks
|
Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the number of participants experiencing one or more adverse events.
|
Baseline to 24, 52 and 104 (End of Study) weeks
|
|
Number of Participants Experiencing Serious Adverse Events (SAEs)
時間枠：Baseline to 24, 52 and 104 (End of Study) weeks
|
Difference between the prostacyclin pathway therapy withdrawal group and the continuation group in the number of participants experiencing one or more serious adverse events.
|
Baseline to 24, 52 and 104 (End of Study) weeks
|
|
Participant Enrollment Rate
時間枠：Baseline to 24 weeks
|
Number of participants enrolled per site per month during the 24-week recruitment period.
|
Baseline to 24 weeks
|
|
Protocol Adherence Rate
時間枠：Baseline to Week 24
|
Proportion of participants who complete study procedures according to protocol through Week 24 without major protocol deviations.
|
Baseline to Week 24
|
|
Completeness of Secondary and Exploratory Outcome Data
時間枠：Baseline to Week 24
|
Proportion of expected secondary and exploratory outcome data points successfully collected through Week 24.
|
Baseline to Week 24
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Dr. Jason Weatherald, MD, MSc, FRCPC、University of Alberta
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。