Treatment With Ambrisentan in Patients With Borderline Pulmonary Arterial Hypertension

NCT04972656 | Recruiting DMC

• 1 other identifier: CSC20210527
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• 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

• Change of Pulmonary vascular resistance

  Pulmonary vascular resistance by right heart catheterization

  baseline, 1 year

Secondary Outcomes (11)

• 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

Study Arms (2)

Ambrisentan

EXPERIMENTAL

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.

Drug: Ambrisentan

Placebo

PLACEBO COMPARATOR

Placebo tablet

Drug: Placebo

Interventions

Ambrisentan DRUG

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.

Ambrisentan

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead
• Tianjin Medical University General Hospital: collaborator

Study Sites (1)

Nanjing First Hospital

Nanjing, Jiangsu, 210006, China

RECRUITING

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Shao-Liang Chen, MD, PhD

  Nanjing First Hospital, Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Zhen-Wen Yang, MD, PhD

CONTACT

+86-13920889629; yzwmd@hotmail.com

Han Zhang, MD, PhD

CONTACT

+86-25-52271330; dxh_nari@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 22, 2021
• Study Start: September 5, 2022
• Primary Completion: December 30, 2025
• Study Completion: March 30, 2026
• Last Updated: September 28, 2022

Record last verified: 2022-09

Locations

CN (1)