Withdrawal of Background Prostacyclin Pathway Therapy in Patients With Pulmonary Arterial Hypertension Receiving Sotatercept: an Open Label Non-inferiority Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible for this study, a participant must meet all of the following criteria:
- •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.
排除标准
- •A potential participant who meets any of the following criteria will be excluded from participation in this study:
- •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.
研究组 & 干预措施
Control group / no change to therapy
The control group will continue prostacyclin pathway therapies as per their authorized indications, with no change in dosage.
Prostacyclin pathway therapy withdrawal
Dose de-escalation and discontinuation of parenteral prostacyclins analogues or selexipag
干预措施: Discontinuation of parenteral prostacyclins analogues or selexipag (Procedure)
结局指标
主要结局
Change in Mean Pulmonary Arterial Pressure (mPAP) From Baseline to 24 Weeks
时间窗: 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.
次要结局
- 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)
- Number of Participants Reporting Prostanoid-Associated Side Effects(Baseline to 24 weeks)