NCT06968962

Comparison of Sequential to Initial Combination Therapy in PAH

A Multicenter, Randomized, Controlled, Double-blind, and Non-inferiority Clinical Trial to Compare the Efficacy of Sequential to Initial Combination Therapy in Patients With Pulmonary Arterial Hypertension

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 376 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, randomized, controlled, double-blind, and non-inferiority clinical trial to compare the efficacy of sequential to initial combination therapy in patients with pulmonary arterial hypertension (PAH). Ambrisentan and Tadalafil will be used in the study. Our research hypothesis is that the efficacy of sequential combination therapy in PAH patients is not inferior to the initial combination therapy as the primary efficacy endpoint is the change in 6MWD at month 12 from baseline.

Detailed description

This is a multicenter, randomized, controlled, double-blind, and non-inferiority clinical trial to compare the efficacy of sequential to initial combination therapy in symptomatic patients with PAH (WHO functional class I-III) and assessed as low-risk or moderate-risk based on 2022 ESC/ERS risk stratification. Subjects must not have previously received chronic PAH therapy (i.e., prostanoids, ERAs, or PDE-5 inhibitors) within 4 weeks prior to Screening. Treatment Escalation 1\. The investigators will conduct a risk stratification assessment based on COMPERA 2.0 every 4 months, i.e. at month 4, 8, and 12. 2\. If the patient meets the low-risk criteria, their current treatment regimen will be maintained, and both the patient and the investigator will be unaware of the specific regimen. 3\. If the patient does not meet the low-risk criteria: 1. No clinical failure events have occurred: The first step is to escalate to blinded dual therapy. 1. The investigator initiates a request for blinded dual therapy, and the pharmacist informs the investigator that the treatment plan has been upgraded as requested. 2. If the patient is currently on mono therapy, the pharmacist will escalate the regimen to dual therapy. 3. If the patient is currently in the initial combination therapy group or has already escalated to blinded dual therapy, the pharmacist will maintain the current dual therapy regimen. 2. If any clinical failure event occurs at any time, as determined by the Clinical Event Evaluation Committee: 1. Escalate to blinded dual therapy as described above 2. Or add prostacyclin analogue 3. Or add IP receptor agonist 4. Or transition of Tadalafil to Riociguat 5. Or add Sotatercept Primary efficacy endpoint is exercise capacity, as the change in 6MWD at month 12 from baseline. Secondary efficacy endpoints will include time to clinical failure events during the 12-month treatment period, and others detailed in outcome measures. Study duration will be approximately 4 years. A non-inferiority test will be conducted based on the mean difference and 95% CI of the change in 6MWD between groups after 12 months of treatment following randomization. An unblinded, external, independent DSMB will monitor participants' data and safety throughout the course of the study.

Conditions

• Pulmonary Arterial Hypertension (PAH)

Interventions

Type	Name	Description
DRUG	Tadalafil	Target dose 40 mg OD
DRUG	Ambrisentan	Target dose 10 mg OD
DRUG	Ambrisentan mimic	Ambrisentan mimic will switch to Ambrisentan if low risk status was not achived at month 4, or 8, or 12.
DRUG	Tadalafil mimic	Tadalafil mimic will switch to Tadalafil if low risk status was not achived at month 4, or 8, or 12.

Timeline

• Start date: 2025-05-14
• Primary completion: 2028-05-01
• Completion: 2028-12-01
• First posted: 2025-05-13
• Last updated: 2025-07-29

Locations

1 site across 1 country: China