Withdrawal of Background Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept: an Open Label Non-inferiority Trial

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join 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 be able to join 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.

Where this trial is running

• University of Alberta Hospital, Edmonton, Alberta, Canada

Who to contact

Canadian VIGOUR Centre Clinical Trial Project Lead · 1-800-707-9098 · waterloo@ualberta.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT07700303.