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

NCT07700303 | Not Yet Recruiting DMC

• 1 other identifier: WATERLOO
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Prostacyclin; sotatercept; open label; non-inferiority; Weatherald; Canadian VIGOUR Centre; CVC; pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (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.

  Baseline to 24 weeks

Secondary Outcomes (6)

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

  Baseline to 24 weeks

• Change in EmPHasis-10 Score From Baseline to Week 24

  Baseline to 24 weeks

• Change in EQ-5D-5L Index Score From Baseline to Week 24

  Baseline to Week 24

• Change in EQ Visual Analogue Scale (EQ VAS) Score From Baseline to Week 24

  Baseline to Week 24

• Change in Living with Medicines Questionnaire Version 3 (LMQ-3) Score From Baseline to Week 24

  Baseline to Week 24

Other Outcomes (5)

• Number of Participants Experiencing Adverse Events (AEs)

  Baseline to 24, 52 and 104 (End of Study) weeks

• Number of Participants Experiencing Serious Adverse Events (SAEs)

  Baseline to 24, 52 and 104 (End of Study) weeks

• Participant Enrollment Rate

  Baseline to 24 weeks

Study Arms (2)

Control group / no change to therapy

NO INTERVENTION

The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.

Prostacyclin pathway therapy withdrawal

EXPERIMENTAL

Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag

Procedure: Discontinuation of parenteral prostacyclins analogues or selexipag

Interventions

Discontinuation of parenteral prostacyclins analogues or selexipag PROCEDURE

Discontinuation of parenteral prostacyclins analogues or selexipag

Prostacyclin pathway therapy withdrawal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, Canada

Location

Related Publications (5)

• 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.

  PMID: 36283952 BACKGROUND

• 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.

  PMID: 40268508 BACKGROUND

• 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.

  PMID: 39978862 BACKGROUND

• 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.

  PMID: 37696565 BACKGROUND

• 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.

  PMID: 36877098 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

selexipag

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dr. Jason Weatherald, MD, MSc, FRCPC

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Canadian VIGOUR Centre Clinical Trial Project Lead

CONTACT

1-800-707-9098; waterloo@ualberta.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2030
• Last Updated: July 15, 2026

Record last verified: 2026-07

Locations

CA (1)