An Investigator initiated trial (IIT) using a prospective, randomized, double-blind, parallel group, placebo-controlled, clinical study design.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
420
Titration: Monotherapy using ambrisentan will be initialized at a beginning dose of 5 mg (once daily). Drug intake is scheduled at the morning. After 4 weeks monitoring, the dose of ambrisentan will be uptitrated to 10 mg once daily. Otherwise, if intolerability is indicated, a dose of 5 mg (once daily) will be maintained through the study duration. Maximum dose allowed: not to exceed 10 mg/day. Administration: Ambrisentan will be administered orally with or without food intake.
Placebo tablet (one to two tablets corresponding to one to two verum tablets). Administration: Placebo will be administrated orally with or without food intake in the morning.
Nanjing First Hospital
Nanjing, Jiangsu, China
RECRUITINGIncidence of diagnostic PAH (mPAP ≥25 mmHg)
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.
Time frame: baseline, 1 year
Change of Pulmonary vascular resistance
Pulmonary vascular resistance by right heart catheterization
Time frame: baseline, 1 year
Re-hospitalization due to clinical worsening
Re-hospitalization is defined as clinical manifestations of worsening PAH requiring re-hospitalization in order to add intravenous pharmacological agents (inotrope or vasodilator), mechanical intervention or ultrafiltration, hemofiltration, or dialysis.
Time frame: baseline, 3 years
All-cause mortality
Time frame: baseline, 3 years
6-Minute-walking Test
Time frame: baseline, 1 year
Right atrial pressure by right heart catheterization
Time frame: baseline, 1 year
Cardiac output (CO) by right heart catheterization
Time frame: baseline, 1 year
Cardiac index (CI) by right heart catheterization
Time frame: baseline, 1 year
RA-area (right atrial area) by echocardiography
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Time frame: baseline, 1 year
RV-area (right ventricular area) by echocardiography
Time frame: baseline, 1 year
Tei by echocardiography
Tei
Time frame: baseline, 1 year
TAPSE (tricuspid annular plane systolic excursion) by echocardiography
Time frame: baseline, 1 year
sPAP (systolic pulmonary arterial pressure) by echocardiography
Time frame: baseline, 1 year