NCT06987097

Ambrisentan for Early Low-Risk Pulmonary Arterial Hypertension

Ambrisentan for the Treatment of Early-Stage Low-Risk Pulmonary Arterial Hypertension: A Multicenter, Randomized, Double-Blind, Placebo-Controlled ALEPH Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 410 (estimated)
• Sponsor: Nanjing First Hospital, Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

Early-stage low-risk PAH is defined as mean pulmonary arterial pressure (mPAP) between 20 and 25 mmHg at rest, measured by right heart catheterization, and classified as low-risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Patients will be randomized at a 1:1 ratio to either the treatment group (Ambrisentan group) or the control group (Placebo group). Treatment group: Ambrisentan, with an initial dose of 5 mg/day (one tablet per day).Control group: Placebo, which will be provided in the same appearance and taste as Ambrisentan, one tablet per day. 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. The study drugs will be administered continuously for 12 months, then unblinding will be performed. Thereafter, patients who have reached the primary endpoint must undertake Ambrisentan. For patients who have not reached the primary endpoint, the subsequent medications treatment will be left at the PAH specialist's discretion. Follow-up will be undertaken at the following timing: Month 1, Month 6, and Month 12, with additional follow-up extending up to 3 years. All clinical drugs involved in this study have completed registration for market approval in China and are currently in clinical use.

Conditions

• Pulmonary Arterial Hypertension (PAH)

Interventions

Type	Name	Description
DRUG	Ambrisentan	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.
DRUG	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.

Timeline

• Start date: 2025-05-15
• Primary completion: 2028-02-28
• Completion: 2029-03-01
• First posted: 2025-05-23
• Last updated: 2025-05-23