Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension (TAPE)

Nanjing Medical University

Status: Enrolling

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Placebo; Drug: Ambrisentan

Study type: Interventional

Funder types: Other

Identifiers

NCT04972656

CSC20210527

Details and patient eligibility

About

An Investigator initiated trial (IIT) using a prospective, randomized, double-blind, parallel group, placebo-controlled, clinical study design.

Full description

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.

Enrollment: 420 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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/1.73m2.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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420 participants in 2 patient groups, including a placebo group

Ambrisentan

Experimental group

Description:

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.

Treatment:

Drug: Ambrisentan

Placebo

Placebo Comparator group

Description:

Placebo tablet

Treatment:

Drug: Placebo