Status:
RECRUITING
Comparison of Sequential to Initial Combination Therapy in PAH
Lead Sponsor:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborating Sponsors:
Huzhou Central Hospital
Ningbo Medical Center Lihuili Hospital
Conditions:
Pulmonary Arterial Hypertension (PAH)
Eligibility:
All Genders
18-80 years
Phase:
NA
Brief 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...
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 (W...
Eligibility Criteria
Inclusion
- Age between 18 to 80 years and weight ≥ 40 kg.
- WHO functional classification I-III.
- Diagnosed with PAH caused or related to the following:
- 1\) Idiopathic PAH 2) Hereditary PAH 3) Associated PAH:
- Connective tissue diseases (e.g., scleroderma, systemic lupus erythematosus, mixed connective tissue disease, etc.)
- Drug or toxin exposure
- Corrected congenital heart diseases for more than 1 year (e.g., atrial septal defect, ventricular septal defect, and patent ductus arteriosus) 4. Risk stratification assessed as low-risk or intermediate-risk according to the 2022 ESC/ERS guidelines.
- 5\. Right heart catheterization meets the following criteria (end-expiratory data, original waveform must be retained for quality control):
- 1\) Mean pulmonary artery pressure ≥ 25 mmHg 2) Pulmonary vascular resistance ≥ 3 Wood units 3) Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg 4) Cardiac output measurement requirements: thermal dilution or direct Fick method; indirect Fick method does not meet study criteria.
- 6\. Pulmonary function tests meet the following criteria:
- 1） Total lung capacity (TLC) ≥ 60% of the predicted normal value; 2） Forced expiratory volume in the first second (FEV1) ≥ 55% of the predicted normal value; 3） DLCO\_SB ≥ 40% of the predicted normal value. 7. Baseline 6MWD more than 100 meters repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value) 8. In a resting state, without supplemental oxygen, arterial oxygen saturation (SaO2) ≥ 88%.
- 9\. No participation in cardiopulmonary rehabilitation training programs within 12 weeks prior to the screening visit.
- 10\. Females of childbearing potential must agree to use contraception until the end of the study.
- 11\. No participation in clinical studies involving other investigational drugs or devices throughout the study duration.
- 12\. Ability to understand the informed consent form and sign it.
Exclusion
- 1\. Other types of pulmonary arterial hypertension (PAH)
- Other types of PAH, such as HIV-related PAH, schistosomiasis-related PAH, etc.
- Pulmonary arterial hypertension associated with portal hypertension
- Pulmonary vein occlusive disease or pulmonary capillary hemangiomatosis 2. Group 4 PH, e.g. Chronic thromboembolic pulmonary hypertension 3. Group 2 PH, i.e., PH associated with left heart disease 4. Group 3 PH, i.e., PH associated with lung disease or hypoxia 5. Group 5 PH, i.e., PH with unclear mechanisms or multi-mechanism 6. PAH Therapy
- 1\) Subjects who have received PAH therapy (such as PDE5 inhibitors, ERAs, or chronic prostacyclin therapy) within 4 weeks prior to the screening visit.
- 2\) Subjects who have ever received ERA therapy (e.g., macitentan) or PDE5 inhibitor therapy (e.g., sildenafil) and discontinued due to tolerance issues unrelated to liver dysfunction.
- 3\) Subjects known to have an allergy to the investigational product, its metabolites, or excipients.
- 7\. Other Therapies
- Subjects who have received intravenous inotropes (e.g., dobutamine) within 2 weeks prior to the screening visit.
- Subjects receiving protease inhibitors, systemic ketoconazole, or systemic itraconazole therapy.
- Subjects receiving strong CYP3A4 inducers (e.g., rifampicin).
- Subjects who have received unstable doses of calcium channel blockers or HMG-CoA reductase inhibitors (statins) within 4 weeks prior to the screening visit (eligible subjects must not have changed doses within 4 weeks prior to the screening visit).
- Subjects with a history of angina or who have received long-acting or short-acting nitrate treatment within the 12 weeks prior to the visit.
- 8\. Laboratory Tests at Screening
- 1） Serum ALT or AST laboratory values \> 2 times the upper limit of normal at screening.
- 2） Serum bilirubin laboratory values \> 1.5 times the upper limit of normal at screening.
- 3） Severe renal impairment (estimated glomerular filtration rate \< 45 mL/min/1.73m3) at screening.
- 9\. Medical History/Current Medical Conditions
- Severe liver dysfunction (Child-Pugh Class C, with or without cirrhosis) at screening.
- Significant anemia in the opinion of the investigator.
- History of bleeding disorders or significant active peptic ulcers.
- Uncontrolled hypertension (≥ 180/110 mmHg) at screening.
- Severe hypotension (\< 90/50 mmHg) at screening.
- Myocardial infarction within 3 months prior to screening.
- Clinically significant aortic or mitral valve disease, constrictive pericarditis, restrictive or congestive cardiomyopathy, life-threatening arrhythmias, significant left ventricular dysfunction, left ventricular outflow tract obstruction, symptomatic coronary artery disease, autonomic hypotension, or circulatory failure.
- History of non-arteritic anterior ischemic optic neuropathy.
- Hereditary degenerative retinal disease (e.g., retinitis pigmentosa).
- Significant fluid retention in the opinion of the investigator.
- Subjects with cardiovascular, liver, kidney, hematologic, gastrointestinal, immune, endocrine, metabolic, or central nervous system diseases that the investigator believes may adversely affect the subject's safety and/or the efficacy of the investigational product or significantly impact the subject's lifespan.
- History of malignant tumors within the past 5 years, except for those with local, non-metastatic basal cell carcinoma, cervical carcinoma in situ, or prostate cancer who are not anticipated to receive radiotherapy, chemotherapy, and/or surgical interventions or initiate hormonal therapy during the study period.
- Pregnant or breastfeeding female subjects.
- Subjects with demonstrated poor compliance.
- History of alcohol abuse or illicit drug use within 1 year.
- Participation in clinical studies involving another investigational drug or device within 4 weeks prior to the screening visit.
- Subjects who fail inclusion/exclusion criteria may be re-screened once.
Key Trial Info
Start Date :
May 14 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2028
Estimated Enrollment :
376 Patients enrolled
Trial Details
Trial ID
NCT06968962
Start Date
May 14 2025
End Date
December 1 2028
Last Update
July 29 2025
Active Locations (1)
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1
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310058