Withdrawal of Background Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept: an Open Label Non-inferiority Trial (WATERLOO)
Pulmonary arterial hypertension (PAH) is a rare lung disease which 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, we 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 patient is doing well on sotatercept is safe. We 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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Canadian VIGOUR Centre Clinical Trial Project Lead
- Telefonní číslo: 1-800-707-9098
- E-mail: waterloo@ualberta.ca
Studijní místa
-
-
Alberta
-
Edmonton, Alberta, Kanada
- University of Alberta Hospital
-
Kontakt:
- CVC Clinical Trial Project Lead
- Telefonní číslo: 1-800-707-9098
- E-mail: waterloo@ualberta.ca
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Žádný zásah: Control group / no change to therapy
The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
|
|
|
Experimentální: Prostacyclin pathway therapy withdrawal
Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
|
Discontinuation of parenteral prostacyclins analogues or selexipag
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time to First Occurrence of All-Cause Death or Clinical Worsening
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Number of Participants Experiencing Adverse Events (AEs)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: Baseline to Week 24
|
Proportion of expected secondary and exploratory outcome data points successfully collected through Week 24.
|
Baseline to Week 24
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Dr. Jason Weatherald, MD, MSc, FRCPC, University of Alberta
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- WATERLOO
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na Plicní arteriální hypertenze
-
University Hospital, Strasbourg, FranceZatím nenabírámeECMO | Mplementace veno-živé VV nebo Veno-Arterial VA | Intenzivní péčeFrancie
-
Medical University of WarsawZatím nenabírámeOnemocnění periferních tepen | Ischemická noha | Stenóza ilické tepny | Embolus ArterialPolsko