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Pulmonary Arterial HypertensionWATERLOONCT07700303

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

A study testing Discontinuation of parenteral prostacyclins analogues or selexipag in people with Pulmonary Arterial Hypertension, run by University of Alberta at 1 site in Canada.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Discontinuation of parenteral prostacyclins analogues or selexipag
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
1 siteCanada
Study dates
30 Oct 2026to 30 Mar 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Principal Investigator contact

1-800-707-9098

weathera@ualberta.ca

Canadian VIGOUR Centre Clinical Trial Project Lead contact

waterloo@ualberta.ca

Canada1 site

  • University of Alberta Hospital

    Edmonton, Alberta

    CVC Clinical Trial Project Lead, 1-800-707-9098, waterloo@ualberta.ca

Other trials in Canada

About this study

Official title: 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.

Being tested
Discontinuation of parenteral prostacyclins analogues or selexipag
Keywords
Prostacyclin, sotatercept, open label, non-inferiority, Weatherald, Canadian VIGOUR Centre, CVC, pulmonary arterial hypertension
Medical subject headings
Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Discontinuation of parenteral prostacyclins analogues or selexipagProcedure or surgery

    Discontinuation of parenteral prostacyclins analogues or selexipag

Study groups in NCT07700303
Study groupRoleWhat they receive
Control group / no change to therapyNo interventionThe control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
Prostacyclin pathway therapy withdrawalExperimentalDose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
Receives: Procedure: Discontinuation of parenteral prostacyclins analogues or selexipag

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Mean Pulmonary Arterial Pressure (mPAP) From 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.

    Measured: Baseline to 24 weeks

Secondary outcomes (6)

  1. Time to First Occurrence of All-Cause Death or Clinical Worsening

    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.

    Measured: Baseline to 24 weeks

  2. Change in EmPHasis-10 Score From Baseline to Week 24

    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.

    Measured: Baseline to 24 weeks

  3. Change in EQ-5D-5L Index Score From 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.

    Measured: Baseline to Week 24

  4. Change in EQ Visual Analogue Scale (EQ VAS) Score From 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.

    Measured: Baseline to Week 24

  5. Change in Living with Medicines Questionnaire Version 3 (LMQ-3) Score From 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.

    Measured: Baseline to Week 24

  6. Number of Participants Reporting Prostanoid-Associated Side Effects

    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.

    Measured: Baseline to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2026
  2. Study start30 Oct 2026 (estimated)
  3. Primary completion30 Mar 2028 (estimated)
  4. Study completion30 Mar 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07700303
Sponsor's protocol ID
WATERLOO
Acronym
WATERLOO
Status last verified
Sep 2026
First submitted
15 Jun 2026
Last updated
23 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 36283952

  • 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.

    PubMed 40268508

  • 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.

    PubMed 39978862

  • 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.

    PubMed 37696565

  • 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.

    PubMed 36877098

Questions about this trial

What is this clinical trial studying?

A study testing Discontinuation of parenteral prostacyclins analogues or selexipag in people with Pulmonary Arterial Hypertension, run by University of Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Principal Investigator (1-800-707-9098, weathera@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks (time frame: Baseline to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07700303, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.

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