A Prospective, Randomized, Open-Label Study Comparing Triple Therapy Versus Sildenafil Dose Optimization in Patients With Pulmonary Arterial Hypertension Using COMPERA 2.0 Risk Stratification as the Primary Outcome
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 196
- 试验地点
- 1
- 主要终点
- Improvement in Risk Stratification According to the COMPERA 2.0 Four-Stratum Model
研究概览
简要总结
Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterized by increased pressure in the pulmonary arteries, leading to right heart failure and premature death. Although combination therapy has improved outcomes, many patients remain at intermediate or high clinical risk despite treatment.
When patients do not reach low-risk status, treatment escalation is recommended. However, different escalation strategies are used in clinical practice, including increasing the dose of existing medications or adding a third drug that targets a different biological pathway. There is limited prospective randomized evidence directly comparing these approaches.
The ASCEND-PAH study is a prospective, randomized, open-label clinical trial designed to compare two therapeutic escalation strategies in adults with PAH who remain at intermediate or high risk despite dual therapy with an endothelin receptor antagonist and sildenafil. Participants will be randomized to either: (1) escalation to triple therapy with the addition of a prostacyclin pathway agent, or (2) optimization of dual therapy by increasing the dose of sildenafil.
The primary objective is to compare the proportion of patients who improve their risk category according to the COMPERA 2.0 four-stratum risk model within 3 to 6 months after randomization. Secondary outcomes include changes in functional status, exercise capacity, biomarkers, clinical worsening, safety, and treatment persistence
详细描述
This is a prospective, randomized, open-label, parallel-group clinical trial designed to evaluate therapeutic escalation strategies in adults with pulmonary arterial hypertension (PAH, Group 1) who remain at intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model despite stable dual therapy.
Eligible participants must be receiving an endothelin receptor antagonist in combination with sildenafil and have a clinical indication for treatment escalation. After confirmation of eligibility and baseline assessments, participants will be randomized in a 1:1 ratio to one of two strategies:
Escalation to triple therapy through addition of a prostacyclin pathway agent (inhaled iloprost or selexipag), according to clinical judgment and availability.
Optimization of dual therapy by increasing the dose of sildenafil according to clinical practice.
Baseline assessments may include WHO functional class, 6-minute walk distance, and BNP or NT-proBNP levels obtained within 90 days prior to randomization. Follow-up evaluation will occur between 3 and 6 months after randomization, with the primary analysis based on the assessment closest to 6 months within that window.
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
盲法说明
This is an open-label study. Neither participants nor investigators are blinded to treatment allocation. No outcome assessors or data analysts are formally masked.
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
- •Diagnosis of pulmonary arterial hypertension (PAH, Group 1) confirmed according to accepted clinical and hemodynamic criteria
- •Stable treatment with an endothelin receptor antagonist in combination with sildenafil prior to randomization
- •Classified as intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model
- •Clinical indication for therapeutic escalation
- •Availability for follow-up assessment between 3 and 6 months after randomization
- •Ability to provide written informed consent
排除标准
- •Participation in another interventional clinical trial that mandates treatment modification
- •Known contraindication to prostacyclin pathway agents (including iloprost or selexipag)
- •Known contraindication to sildenafil dose escalation
- •Pregnancy or breastfeeding
- •Women of childbearing potential not using effective contraception
- •Any clinical condition that, in the investigator's judgment, would interfere with study participation or outcome assessment
研究组 & 干预措施
Sildenafil Dose Optimization
Participants will continue dual therapy with an endothelin receptor antagonist and sildenafil, with optimization of sildenafil dose according to clinical practice. No additional pulmonary arterial hypertension pathway agent will be added at randomization. Treatment adjustments after randomization will be recorded if clinically required.
干预措施: Sildenafil Dose Optimization (Drug)
结局指标
主要结局
Improvement in Risk Stratification According to the COMPERA 2.0 Four-Stratum Model
时间窗: Between 3 and 6 months after randomization (assessment closest to 6 months within the predefined window)
Proportion of participants who achieve improvement in clinical risk category between baseline and follow-up, defined as a decrease of at least one risk category according to the COMPERA 2.0 four-stratum model (low, intermediate-low, intermediate-high, high risk). Risk status is determined using World Health Organization functional class, 6-minute walk distance, and BNP or NT-proBNP levels, when available.
次要结局
- Composite Clinical Improvement at 3-6 Months(Between 3 and 6 months after randomization)
- Treatment Persistence(From randomization through 6 months of follow-up)
- Composite Clinical Worsening(From randomization through 6 months of follow-up)
- Change in WHO Functional Class(Between 3 and 6 months after randomization)
- Change in 6-Minute Walk Distance (6MWD)(Between 3 and 6 months after randomization)
- Change in BNP or NT-proBNP Levels(Between 3 and 6 months after randomization)
- Time to Clinical Worsening(From randomization through 6 months of follow-up)
- Safety and Adverse Events(From randomization through 6 months)
研究者
Caio Júlio César dos Santos Fernandes
Principal Investigator
University of Sao Paulo General Hospital