Pulmonary Arterial Hypertension
Conditions
Keywords
Prostacyclin, sotatercept, open label, non-inferiority, Weatherald, Canadian VIGOUR Centre, CVC, pulmonary arterial hypertension
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.
Interventions
PROCEDUREDiscontinuation of parenteral prostacyclins analogues or selexipag
Discontinuation of parenteral prostacyclins analogues or selexipag
Sponsors
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of All-Cause Death or Clinical Worsening | 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. |
| Change in EmPHasis-10 Score From Baseline to Week 24 | 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. |
| Change in EQ-5D-5L Index Score From Baseline to Week 24 | 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. |
| Change in EQ Visual Analogue Scale (EQ VAS) Score From Baseline to Week 24 | 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. |
| Change in Living with Medicines Questionnaire Version 3 (LMQ-3) Score From Baseline to Week 24 | 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. |
| Number of Participants Reporting Prostanoid-Associated Side Effects | 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. |
Countries
Canada
Contacts
CONTACTCanadian VIGOUR Centre Clinical Trial Project Lead
PRINCIPAL_INVESTIGATORDr. Jason Weatherald, MD, MSc, FRCPC
University of Alberta
Outcome results
None listed