ACTION - The Impact of ERA Switching on Risk Stratification in Pulmonary Arterial Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 183
- 试验地点
- 1
- 主要终点
- Change in risk category according to used scores
研究概览
简要总结
Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially life-threatening disease characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, and right ventricular dysfunction. The endothelin pathway plays a central role in its pathophysiology and is targeted by endothelin receptor antagonists (ERAs), including ambrisentan and bosentan.
Ambrisentan is a selective ETA receptor antagonist, whereas bosentan blocks both ETA and ETB receptors. Although transitions between ERAs occur in clinical practice, evidence regarding the clinical impact of switching from ambrisentan to bosentan remains limited.
ACTION is a retrospective, observational, single-center cohort study evaluating adult patients with pulmonary arterial hypertension (World Health Organization Group 1) and/or chronic thromboembolic pulmonary hypertension (World Health Organization Group 4) confirmed by right heart catheterization. Patients who switched from ambrisentan to bosentan because of a national ambrisentan shortage will be compared with clinically similar patients who remained on ambrisentan.
Clinical, functional, and laboratory data recorded at baseline and at 3 to 6 months of follow-up will be assessed. The primary outcome is the proportion of patients with worsening risk stratification after switching from ambrisentan to bosentan compared with patients who continued ambrisentan. Risk will be evaluated using the COMPERA 2.0 and REVEAL Lite 2 assessment tools.
Secondary outcomes include changes in World Health Organization/New York Heart Association functional class, 6-minute walk distance, BNP levels, individual risk-assessment components, hepatic enzymes, hemoglobin levels, and clinically relevant events such as hospitalization, emergency department visits, initiation of supplemental oxygen, and right heart failure decompensation.
详细描述
Pulmonary arterial hypertension (PAH) is a progressive and potentially life-threatening condition characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, right ventricular dysfunction, and premature mortality. Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as World Health Organization Group 4. In selected patients with PAH or inoperable or residual CTEPH, therapies targeting the endothelin pathway may be used as part of clinical management.
Endothelin-1 contributes to pulmonary vasoconstriction and vascular remodeling through ETA and ETB receptors. Endothelin receptor antagonists are an established component of PAH treatment. Ambrisentan selectively antagonizes the ETA receptor and is administered once daily, whereas bosentan is a dual ETA/ETB receptor antagonist that requires regular monitoring because of its potential hepatic and hematologic adverse effects.
Transitions between medications within the ERA class may occur because of adverse events, clinical considerations, patient-related factors, or medication availability. However, evidence regarding the clinical consequences of switching from ambrisentan to bosentan is limited, particularly when the transition is imposed by an external disruption in medication supply rather than planned as an elective therapeutic strategy.
The ACTION study is a retrospective, observational, single-center cohort study designed to assess the real-world clinical impact of switching from ambrisentan to bosentan. The study includes adults aged 18 years or older with PAH or CTEPH confirmed by right heart catheterization. Two exposure groups will be evaluated: patients who transitioned from ambrisentan 10 mg to bosentan 125 mg following a national shortage of ambrisentan and patients with a similar clinical profile who remained on ambrisentan.
Baseline data will correspond to the clinical assessment performed at or near the time of the medication transition in the switch group and to a comparable reference assessment in the maintenance group. Follow-up data recorded 3 to 6 months later will be used to evaluate changes within each group and differences between groups.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •Age ≥ 18 years
- •Confirmed diagnosis of pulmonary arterial hypertension (PAH) by right heart catheterization
- •Documented therapeutic switch from ambrisentan (10 mg once daily) to bosentan (125 mg twice daily) within the previous 6 months for the switch group
- •Treatment with ambrisentan for at least 6 months without switching to bosentan for the maintenance group
排除标准
- •History of severe hepatic impairment
- •Incomplete clinical or laboratory records that prevent risk score calculation
- •Inability to attend clinical follow-up between 3 and 6 months after medication switch
结局指标
主要结局
Change in risk category according to used scores
时间窗: 3 to 6 months after Endotelin Receptor Antagonist switch
Proportion of patients who change their clinical risk category (improvement, worsening, or no change) based on scores between baseline (at the time of medication switch) and follow-up (3 to 6 months after the switch from ambrisentan to bosentan).
Change in risk category according to used scores
时间窗: From 3 to 6 months
Proportion of participants with worsening clinical risk category from baseline to follow-up, comparing patients who switched from ambrisentan to bosentan with patients who remained on ambrisentan..
次要结局
- Change in Functional Class(3 to 6 months after Endotelin Receptor Antagonist switch)
- Change in 6-Minute Walk Distance (6MWD)(3 to 6 months after ERA switch)
- Change in NT-proBNP Levels(3 to 6 months after ERA switch)
- Incidence of Hepatotoxicity(3 to 6 months after ERA switch)
- Change in Hemoglobin Levels(3 to 6 months after ERA switch)
- Change in Individual Parameters of risk stratification(3 to 6 months after Endotelin Receptor Antagonist switch)
- Change in Functional Class(3 to 6 months)
- Change in 6-Minute Walk Distance (6MWD)(3 to 6 months)
- Change in NT-proBNP Levels(3 to 6 months)
- Incidence of Hepatotoxicity(3 to 6 months)
- Change in Hemoglobin Levels(3 to 6 months)
- Change in Individual Parameters of risk stratification(3 to 6 months)
研究者
Caio Júlio César dos Santos Fernandes
PhD
University of Sao Paulo General Hospital