Actively Recruiting
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
Led by Second Affiliated Hospital, School of Medicine, Zhejiang University · Updated on 2025-07-29
376
Participants Needed
1
Research Sites
30 weeks
Total Duration
On this page
Sponsors
S
Second Affiliated Hospital, School of Medicine, Zhejiang University
Lead Sponsor
H
Huzhou Central Hospital
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are conducting a multicenter, randomized, controlled, double-blind trial to compare the effects of sequential versus initial combination therapy in patients with pulmonary arterial hypertension (PAH). The study focuses on symptomatic patients classified as low or moderate risk by 2022 guidelines, who have not received chronic PAH treatments recently. The primary goal is to determine if the sequential combination therapy is not less effective than starting with combination therapy, measured by changes in walking distance after 12 months. Participants will receive treatments involving Ambrisentan and Tadalafil. One group receives both drugs immediately after randomization, while two other groups start with one drug and add the other sequentially if low-risk status is not achieved at 4, 8, or 12 months. Risk assessments occur every four months, and treatment may be escalated based on clinical failure or risk status, including options to add other therapies or switch medications. During the study, participants will undergo regular risk evaluations, walking distance tests, blood tests, and assessments of heart and lung function at baseline and multiple time points up to 12 months. Researchers will monitor safety continuously with an independent board. The study duration is about four years, focusing on exercise capacity changes and clinical event timing as key outcomes.
CONDITIONS
Brief Title
Comparison of Sequential to Initial Combination Therapy in PAH
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 to 80 years and weight 240 kg
- WHO functional classification I-III
- Diagnosed with idiopathic, hereditary, or associated PAH due to connective tissue disease, drug/toxin exposure, or corrected congenital heart diseases over 1 year
- Low-risk or intermediate-risk based on 2022 ESC/ERS guidelines
- Right heart catheterization meeting specified pressure and resistance criteria
- Pulmonary function tests meeting specific lung capacity and volume thresholds
- Baseline six-minute walk distance over 100 meters with consistent repeated measures
- Resting arterial oxygen saturation (SaO2) at least 88% without supplemental oxygen
- No participation in cardiopulmonary rehabilitation within 12 weeks prior
- Females of childbearing potential must agree to contraception until study end
- No participation in other investigational drug or device studies during trial
- Ability to understand and sign informed consent
You will not qualify if you...
- Other types of pulmonary arterial hypertension such as HIV-related or portal hypertension associated
- Pulmonary hypertension groups 2, 3, 4, or 5 conditions
- PAH therapy within 4 weeks prior to screening or intolerance to ERA or PDE5 inhibitors
- Allergy to investigational products or excipients
- Recent use of intravenous inotropes or certain medications like protease inhibitors or strong CYP3A4 inducers
- Unstable doses of calcium channel blockers or statins within 4 weeks
- Recent angina or nitrate treatment within 12 weeks
- Elevated liver enzymes or bilirubin beyond specified limits
- Severe renal impairment or liver dysfunction
- Significant anemia, bleeding disorders, or active ulcers
- Uncontrolled blood pressure or recent heart attack
- Serious heart valve or muscle diseases, arrhythmias, or coronary artery disease
- History of optic neuropathy or hereditary retinal disease
- Significant fluid retention or other serious medical conditions affecting safety or efficacy
- Recent history of malignant tumors except certain local cancers
- Pregnant or breastfeeding females
- Poor compliance history
- Alcohol abuse or illicit drug use within 1 year
- Participation in other investigational studies within 4 weeks prior to screening
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 12 months
Participants receive either initial dual combination therapy with Ambrisentan and Tadalafil immediately after randomization, or sequential combination therapy starting with a mimic drug followed by addition of active drug if low-risk status is not achieved at months 4, 8, or 12. Risk stratification assessments occur every 4 months to guide treatment escalation as needed.
Visits at baseline and months 4, 8, and 12
Duration - Up to 3 years after treatment
Participants are monitored for clinical failure events and treatment response after the 12-month treatment period as part of the overall 4-year study duration.
Periodic assessments depending on study schedule
Trial Site Locations
Total: 1 location
1
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310058
Actively Recruiting
Research Team
Z
Zongye Cai, MD, PhD
Z
Zexin Chen
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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