Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension: a Multicenter, Randomized, Double-blind, Placebo-controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 420
- 试验地点
- 1
- 主要终点
- Incidence of diagnostic PAH (mPAP ≥25 mmHg)
研究概览
简要总结
An Investigator initiated trial (IIT) using a prospective, randomized, double-blind, parallel group, placebo-controlled, clinical study design.
详细描述
The treatment options and prognosis of patients with borderline pulmonary arterial hypertension (PAH) defined as mean pulmonary arterial pressure (mPAP) between 21-24 mm Hg measured by right heart catheterization (RHC) are understudied. The objective of this study is to determine the treatment effect of endothelin-receptor antagonist (Ambrisentan) for patients with borderline PAH when comparing with placebo. Accordingly, 420 patients with borderline PAH will be included in this prospective, randomized, double- blind, parallel group, placebo-controlled study. Repeat screening is required if last screening was performed > 30 days ago. Baseline medical history will be obtained and physical examination will be conducted before signed consent and randomization. Moreover, an electrocardiogram (ECG), laboratory testing, and transthoracic echocardiography (TTE) at supine will be carried out before randomization and during follow-up. Subjects have to meet all inclusion criteria and have no anyone of exclusion criteria. This study will comprise 3 stages: 1) screening period (0-30 days), 2) 1-year study period (365 ± 30 days), 3) extended follow-up duration 3 years ± 30 days. Repeat measurements of cardiac function, hemodynamic, exercise capacity, and clinical events will be scheduled at the end of study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subject must be age ≥18 years;
- •Subject has mPAP 21-24 mmHg, and PAWP<15mmHg.The underlying diseases that cause critical PAH belong to the first group, which is divided into: Idiopathic pulmonary hypertension, hereditary pulmonary hypertension, drugs and poisons associated with pulmonary hypertension, connective tissue diseases associated with pulmonary hypertension, HIV infection associated with pulmonary hypertension, portal hypertension associated with pulmonary hypertension, tumors associated with pulmonary hypertension, congenital heart disease associated with pulmonary hypertension.
- •Subject (or legal guardian) understands the trial design and treatment procedures and provides written informal consent before any trial-specific tests or procedures are performed.
排除标准
- •Pulmonary hypertension (PH) confirmed by right heart catheter (RHC) before enrolment, i.e. mPAP ≥25 mmHg at rest.
- •Ongoing or a history of >2 weeks of continued use of therapies that are considered definitive PH treatment: endothelin receptor antagonists (ERA; e.g. bosentan, ambrisentan), phosphodiesterase type 5 inhibitors (PDE5; e.g. sildenafil, tadalafil, vardenafil), prostanoids (e.g. epoprostenol, treprostinil, iloprost, beraprost) and soluble guanylate cyclase stimulator (e.g. Riociguat). Intermittent use of PDE5 inhibitors for male erectile dysfunction is permitted.
- •Known intolerance to ambrisentan or one of its excipients.
- •Pulmonary vein occlusive disease
- •Pulmonary capillary hemangiomatosis
- •Surgical repair or interventional occlusion of congenital heart disease within 6 months prior to screening of this study
- •Active connective tissue diseases
- •Pulmonary hypertension due to left heart disease
- •Pulmonary hypertension due to pulmonary disease and/or hypoxia
- •Acute pulmonary embolism and/or chronic thromboembolism
- •Clinically significant anemia, defined as hemoglobin concentration 75% below the normal lower limit.
- •Renal insufficiency was defined as glomerular filtration rate [EGFR] <30 mL/min/1.73m
- •Transaminase (ALT and/or AST) increased, exceeding the upper limit of normal value by 3 times.
- •Arterial systolic blood pressure < 85 mmHg.
- •Uncontrolled hypertension, defined as blood pressure >160/90 mmHg (resting state) and/or >220/120 mmHg (load state).
- •Participate in any drug clinical trial within 4 weeks prior to screening in this study and/or plan to participate in another drug clinical trial during the study period.
- •Pregnant or lactating women.
研究组 & 干预措施
Ambrisentan
Monotherapy using ambrisentan will start at a dose of 5 mg (once daily) and will be up-titrated to 10 mg (once daily) after 4 weeks apart if patients are tolerable.
干预措施: Ambrisentan (Drug)
Placebo
Placebo tablet
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of diagnostic PAH (mPAP ≥25 mmHg)
时间窗: baseline, 1 year
Determine whether mean pulmonary arterial pressure of patients with borderline - PAH (mPAP 21-24 mmHg) can be reduced by 3 mm Hg (absolute change baseline vs. 1 year; equals 15%) following treatment with ambrisentan 10 mg/die (initiated with 5 mg/die and elevated up to 10 mg/die) over 1 year (primary endpoint) compared to baseline and placebo.
Change of Pulmonary vascular resistance
时间窗: baseline, 1 year
Pulmonary vascular resistance by right heart catheterization
次要结局
- Re-hospitalization due to clinical worsening(baseline, 3 years)
- All-cause mortality(baseline, 3 years)
- 6-Minute-walking Test(baseline, 1 year)
- Right atrial pressure by right heart catheterization(baseline, 1 year)
- Cardiac output (CO) by right heart catheterization(baseline, 1 year)
- Cardiac index (CI) by right heart catheterization(baseline, 1 year)
- RA-area (right atrial area) by echocardiography(baseline, 1 year)
- RV-area (right ventricular area) by echocardiography(baseline, 1 year)
- sPAP (systolic pulmonary arterial pressure) by echocardiography(baseline, 1 year)
- Tei by echocardiography(baseline, 1 year)
- TAPSE (tricuspid annular plane systolic excursion) by echocardiography(baseline, 1 year)
研究者
HangZhang
Professor
Nanjing First Hospital, Nanjing Medical University