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

Primary Purpose

Pulmonary Arterial Hypertension

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Ambrisentan

Placebo

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Nanjing First HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ambrisentan

Placebo

Arm 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.

Placebo tablet

Outcomes

Primary Outcome Measures

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.

Change of Pulmonary vascular resistance

Pulmonary vascular resistance by right heart catheterization

Secondary Outcome Measures

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.

All-cause mortality

6-Minute-walking Test

Right atrial pressure by right heart catheterization

Cardiac output (CO) by right heart catheterization

Cardiac index (CI) by right heart catheterization

RA-area (right atrial area) by echocardiography

RV-area (right ventricular area) by echocardiography

Tei by echocardiography

Tei

TAPSE (tricuspid annular plane systolic excursion) by echocardiography

sPAP (systolic pulmonary arterial pressure) by echocardiography

Full Information

NCT ID

NCT04972656

First Posted

July 9, 2021

Last Updated

September 27, 2022

Sponsor

Nanjing First Hospital, Nanjing Medical University

Collaborators

Tianjin Medical University General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04972656

Brief Title

Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension

Acronym

TAPE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 5, 2022 (Actual)

Primary Completion Date

December 30, 2025 (Anticipated)

Study Completion Date

March 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Nanjing First Hospital, Nanjing Medical University

Collaborators

Tianjin Medical University General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

420 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ambrisentan

Arm Type

Experimental

Arm 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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo tablet

Intervention Type

Drug

Intervention Name(s)

Ambrisentan

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of diagnostic PAH (mPAP ≥25 mmHg)

Description

Time Frame

baseline, 1 year

Title

Change of Pulmonary vascular resistance

Description

Pulmonary vascular resistance by right heart catheterization

Time Frame

baseline, 1 year

Secondary Outcome Measure Information:

Title

Re-hospitalization due to clinical worsening

Description

Time Frame

baseline, 3 years

Title

All-cause mortality

Time Frame

baseline, 3 years

Title

6-Minute-walking Test

Time Frame

baseline, 1 year

Title

Right atrial pressure by right heart catheterization

Time Frame

baseline, 1 year

Title

Cardiac output (CO) by right heart catheterization

Time Frame

baseline, 1 year

Title

Cardiac index (CI) by right heart catheterization

Time Frame

baseline, 1 year

Title

RA-area (right atrial area) by echocardiography

Time Frame

baseline, 1 year

Title

RV-area (right ventricular area) by echocardiography

Time Frame

baseline, 1 year

Title

Tei by echocardiography

Description

Tei

Time Frame

baseline, 1 year

Title

TAPSE (tricuspid annular plane systolic excursion) by echocardiography

Time Frame

baseline, 1 year

Title

sPAP (systolic pulmonary arterial pressure) by echocardiography

Time Frame

baseline, 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhen-Wen Yang, MD, PhD

Phone

+86-13920889629

yzwmd@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Han Zhang, MD, PhD

Phone

+86-25-52271330

dxh_nari@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shao-Liang Chen, MD, PhD

Organizational Affiliation

Nanjing First Hospital, Nanjing Medical University

Official's Role

Study Chair

Facility Information:

Facility Name

Nanjing First Hospital

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210006

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shao-Liang Chen, PHD

Phone

02552271350

chmengx@126.com

First Name & Middle Initial & Last Name & Degree

Hang Zhang, PHD

Phone

02552271330

dxh_nari@sina.com

12. IPD Sharing Statement

Learn more about this trial

Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension

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