Ambrisentan for Early Low-Risk Pulmonary Arterial Hypertension

NCT06987097 | Not Yet Recruiting DMC

• 1 other identifier: KY20250327-11
• Study Type: interventional
• Target: 410
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial.

Conditions

Pulmonary Arterial Hypertension (PAH)

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the composite of pulmonary hypertension progression at 12 months

  defined as meeting any of the following criteria within 12 months: 1. mPAP ≥ 25 mmHg OR PVR \> 3 WUs as measured by RHC OR 2. worsening of risk stratification compared to baseline, defining as at least one class progression based on the simplified four-tier model of the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

  baseline,12 months

Secondary Outcomes (22)

• systolic PAP (sPAP) by Hemodynamic measurements

  baseline,12 months

• mPAP by Hemodynamic measurements

  baseline,12 months

• cardiac output (CO) by Hemodynamic measurements

  baseline,12 months

• cardiac index (CI) by Hemodynamic measurements

  baseline,12 months

• PVR by Hemodynamic measurements

  baseline,12 months

Study Arms (2)

Ambrisentan

EXPERIMENTAL

Monotherapy using ambrisentan will start at a dose of 5 mg (once daily) and will be up-titrated to 10mg (once daily) after 2 weeks apart if patients are tolerable.

Drug: Ambrisentan

Placebo Placebo tablet

PLACEBO COMPARATOR

Placebo tablet (one to two tablets corresponding to one to two verum tablets).

Drug: Placebo

Interventions

Ambrisentan DRUG

After two weeks of initial treatment, the study drugs' dose will be increased to two tablets per day (10 mg/day). If the patient cannot tolerate the increased dose (e.g., experiencing headache, dizziness, palpitations, hypotension, or other drug-related symptoms or signs), the dose will be reduced to 5 mg/day. If the study drug has reached the maximum allowable dose (two tablets/day) and the patient shows signs of worsening PAH or right heart failure, the clinician may decide to add diuretics (with the type and dosage left at the referring physician's discretion). The number and percentage of patients requiring diuretic combination therapy in both groups will be recorded. Other baseline treatment medications will remain unchanged through follow-up duration.

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 Placebo tablet

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years;
• mPAP \> 20 mmHg and \< 25 mmHg, pulmonary vascular resistance (PVR) \> 2 WUs and ≤ 3 WUs, and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg via right heart catheterization (RHC); RHC measurement will be accepted if it was done within 7 days before enrollment;
• Group I PAH, including idiopathic PAH (IPAH), heritable PAH (HPAH), Drug- and toxin-induced PAH, associated with connective tissue disease (connective tissue disease at good control), associated with portal hypertension, associated with congenital heart disease;
• At low risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension three-strata risk-assessment model;
• The subject or a legally authorized representative must understand the study requirements, agree to the treatment procedures, and provide written informed consent before any study-specific procedures are performed;
• The subject must demonstrate a willingness and ability to comply with all protocol requirements.

You may not qualify if:

• Patients currently receiving PAH specific medications, regardless of whether mPAP is between 20-25 mmHg. PAH specific medications include endothelin receptor antagonists (ERAs; e.g., bosentan, ambrisentan, macitentan), phosphodiesterase type 5 inhibitors (PDE5i; e.g., sildenafil, tadalafil, vardenafil), prostacyclin analogs (e.g., iloprost, epoprostenol, treprostinil, beraprost), soluble guanylate cyclase stimulators (e.g., riociguat). Intermittent use of PDE5 inhibitors for the treatment of male erectile dysfunction is permitted;
• Intolerance to ambrisentan or its excipients;
• Pulmonary veno-occlusive disease (PVOD);
• Pulmonary capillary hemangiomatosis (PCH);
• Within 6 months after congenital heart disease surgical repair or percutaneous closure procedure;
• Group II-V PH;
• Clinically significant anemia, defined as hemoglobin concentration below 75% of the lower limit of normal;
• Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m² within 3 months prior to enrollment;
• Elevated Alanine Aminotransferase （ALT） and/or Aspartate Aminotransferase （AST） exceeding 3 times the upper limit of normal (ULN);
• Systolic blood pressure \< 85 mmHg;
• Uncontrolled hypertension, defined as blood pressure \> 160/90 mmHg at rest and/or \> 220/120 mmHg under stress conditions;
• Participation in any clinical drug trial within 4 weeks prior to screening and/or planned participation in another clinical drug trial during this study;
• Expected life expectancy of less than 1 year;
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead

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

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: April 24, 2025
• First Posted: May 23, 2025
• Study Start: May 15, 2025
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share