Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

Withdrawal of Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept (WATERLOO) (WATERLOO)

13 juli 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Geschat)

78

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

  • Naam: Canadian VIGOUR Centre Clinical Trial Project Lead
  • Telefoonnummer: 1-800-707-9098
  • E-mail: waterloo@ualberta.ca

Studie Locaties

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • University of Alberta Hospital
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria: In order to be eligible for this study, a participant must meet all of the following criteria:

  1. Adults ≥ 18 years old diagnosed with PAH.
  2. Treatment with sotatercept for ≥6 months.
  3. Background therapy with ≥2 PAH vasodilator therapies, one of which is a parenteral prostacyclin or selexipag.
  4. At low or intermediate-low risk, defined using the 2022 ESC/ERS guidelines 4-strata risk assessment tool (Table 1).
  5. 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
  6. The ability to adhere to the study visit schedule and to comprehend and comply with all protocol requirements.
  7. 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:

  1. Known intolerance to sotatercept
  2. 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.
  3. Hospitalization for worsening PAH or right heart failure within the 3 months prior to screening.
  4. Active listing for lung or heart/lung transplantation.
  5. Metastatic cancer or any other condition with a life expectancy < 6 months,
  6. Female patients who are pregnant or who are of childbearing age and are unwilling to use contraception during the study.
  7. History of ≥ 3 interruptions or missed doses of sotatercept for any reason within the previous 6 months prior to screening.
  8. 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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Geen tussenkomst: Control group / no change to therapy
The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
Experimenteel: Prostacyclin pathway therapy withdrawal
Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
Procedure: Discontinuation of parenteral prostacyclins analogues or selexipag
Discontinuation of parenteral prostacyclins analogues or selexipag

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time to First Occurrence of All-Cause Death or Clinical Worsening
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants Experiencing Adverse Events (AEs)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Baseline to Week 24
Proportion of expected secondary and exploratory outcome data points successfully collected through Week 24.
Baseline to Week 24

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of Alberta

Onderzoekers

  • Hoofdonderzoeker: Dr. Jason Weatherald, MD, MSc, FRCPC, University of Alberta

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

30 september 2026

Primaire voltooiing (Geschat)

30 maart 2028

Studie voltooiing (Geschat)

30 maart 2030

Studieregistratiedata

Eerst ingediend

15 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

8 juli 2026

Eerst geplaatst (Werkelijk)

14 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 juli 2026

Laatste update ingediend die voldeed aan QC-criteria

13 juli 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • WATERLOO

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren