Withdrawal of Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept (WATERLOO) (WATERLOO)
2026년 7월 13일 업데이트: University of Alberta
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.
연구 개요
상태
상태
아직 모집하지 않음
정황
정황
개입 / 치료
개입 / 치료
연구 유형
연구 유형
중재적
등록 (추정된)
등록
78
단계
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
연구 연락처
- 이름: Canadian VIGOUR Centre Clinical Trial Project Lead
- 전화번호: 1-800-707-9098
- 이메일: waterloo@ualberta.ca
연구 장소
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Alberta
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Edmonton, Alberta, 캐나다
- University of Alberta Hospital
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연락하다:
- CVC Clinical Trial Project Lead
- 전화번호: 1-800-707-9098
- 이메일: waterloo@ualberta.ca
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
설명
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.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
2
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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간섭 없음: 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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실험적: 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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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
기간: 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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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Time to First Occurrence of All-Cause Death or Clinical Worsening
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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기타 결과 측정
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Number of Participants Experiencing Adverse Events (AEs)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
수사관
- 수석 연구원: Dr. Jason Weatherald, MD, MSc, FRCPC, University of Alberta
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
연구 시작
2026년 9월 30일
기본 완료 (추정된)
기본 완료
2028년 3월 30일
연구 완료 (추정된)
연구 완료
2030년 3월 30일
연구 등록 날짜
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처음 게시됨 (실제)
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연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
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마지막으로 확인됨
마지막으로 확인됨
2026년 7월 1일
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
기타 연구 ID 번호
- WATERLOO
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
미정
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
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아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .