Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— TAPE  

Official title:

Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension: a Multicenter, Randomized, Double-blind, Placebo-controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04972656
• Other study ID #: CSC20210527
• Status: Recruiting
• Phase: N/A
• Start date: September 5, 2022
• Est. completion date: March 30, 2026

Study information

• Verified date: September 2022
• Source: Nanjing First Hospital, Nanjing Medical University
• Contact: Zhen-Wen Yang, MD, PhD
• Phone: +86-13920889629
• Email: yzwmd[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: March 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Ambrisentan
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
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.

Locations

Country	Name	City	State
China	Nanjing First Hospital	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Nanjing First Hospital, Nanjing Medical University	Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence 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.	baseline, 1 year
Primary	Change of Pulmonary vascular resistance	Pulmonary vascular resistance by right heart catheterization	baseline, 1 year
Secondary	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.	baseline, 3 years
Secondary	All-cause mortality		baseline, 3 years
Secondary	6-Minute-walking Test		baseline, 1 year
Secondary	Right atrial pressure by right heart catheterization		baseline, 1 year
Secondary	Cardiac output (CO) by right heart catheterization		baseline, 1 year
Secondary	Cardiac index (CI) by right heart catheterization		baseline, 1 year
Secondary	RA-area (right atrial area) by echocardiography		baseline, 1 year
Secondary	RV-area (right ventricular area) by echocardiography		baseline, 1 year
Secondary	Tei by echocardiography	Tei	baseline, 1 year
Secondary	TAPSE (tricuspid annular plane systolic excursion) by echocardiography		baseline, 1 year
Secondary	sPAP (systolic pulmonary arterial pressure) by echocardiography		baseline, 1 year