Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study aims to compare the effectiveness and safety of two treatment approaches for patients with severe pulmonary hypertension: standard targeted drug therapy alone, and a combination of standard targeted drugs plus Qishen Yiqi Dropping Pills over 52 weeks of treatment.
Pulmonary hypertension is a chronic condition that raises blood pressure in the lung arteries, causing symptoms like shortness of breath, tiredness, and difficulty with physical activity. While targeted drug treatments are available, many patients still experience persistent symptoms and reduced quality of life. This study will enroll patients with severe pulmonary hypertension to see if adding Qishen Yiqi Dropping Pills to standard treatment can improve patient outcomes.
Participants will be randomly assigned to one of two groups: the combination treatment group will receive Qishen Yiqi Dropping Pills plus standard targeted drugs, and the control group will receive standard targeted drugs alone. All participants will be followed for 52 weeks, during which we will regularly assess:
A single-center, parallel, randomized, controlled trial will be conducted to evaluate the efficacy and safety of Qishen Yiqi Dropping Pills combined with western medicine therapy compared with western medicine therapy alone in Asian patients with pulmonary hypertension. A total of 120 pulmonary hypertension patients aged 18-75 years will be recruited into the study in Guangdong Provincial People's Hospital. After a screening period of no more than 2 weeks, patients will be randomly assigned to the Qishen Yiqi Dropping Pills 0.5g three times daily plus targeted drug therapy group or the targeted drug therapy alone group in a 1:1 ratio. All patients in both groups will receive treatment for 52 weeks, and participants will be followed for 26 weeks after the end of treatment. The primary outcomes are the changes in patients' quality of life score, 6-minute walk distance, and Borg score.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Comparator: QSYQ Pills + targeted monotherapy group | Experimental | Patients in this arm will receive a 12-week period of Qishen Yiqi Dropping Pills 0.5g orally three times daily (tid) in combination with targeted monotherapy. |
|
| Active Comparator: targeted monotherapy group | Active Comparator | Patients in this arm will receive a 12-week period of targeted monotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Qishen Yiqi Dropping Pills 0.5g Oral Three Times Daily + Targeted Therapy for Pulmonary Arterial Hypertension | Drug | Experimental Group: Qishen Yiqi Dropping Pills combined with standard PAH-targeted therapy. Qishen Yiqi Dropping Pills is an NMPA-approved Chinese patent medicine for cardiovascular diseases, each pill is 0.5g, main ingredients include astragalus membranaceus, salvia miltiorrhiza, panax notoginseng and dalbergia odorifera. Administration: 0.5g orally tid after meals. Targeted therapy follows *2021 Chinese PAH Diagnosis and Treatment Guidelines*, including one or more approved PAH-targeted agents at clinically recommended doses. Total treatment duration: 26weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in 6-Minute Walk Distance (6MWD) at 52 Weeks | The 6-Minute Walk Test (6MWT) is a standardized, objective measure of functional exercise capacity commonly used in cardiovascular disease populations. Participants will be instructed to walk as far as possible on a flat, 30-meter long corridor for a total duration of 6 minutes, with the total distance covered (in meters) recorded as the 6-Minute Walk Distance (6MWD). The change in 6MWD from baseline to the end of the treatment period will be calculated as the primary efficacy endpoint, with a greater increase indicating better improvement in cardiopulmonary function and exercise tolerance. | Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks， 52weeks (end of treatment) |
| Change from Baseline in Seattle Angina Questionnaire (SAQ) Score at 52 Weeks | The Seattle Angina Questionnaire (SAQ) is a validated, disease-specific quality of life measure for patients with cardiovascular disease, covering 5 domains: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. Each domain score ranges from 0 to 100, with higher scores indicating better health status and less symptom burden. The change in total SAQ score from baseline to the end of follow-up will be calculated as the primary efficacy endpoint. | Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks， 52weeks (end of follow-up) |
| Change from Baseline in Borg Rating of Perceived Exertion (RPE) Scale Score at 52 Weeks | The Borg Rating of Perceived Exertion (RPE) Scale is a widely used, validated self-report measure of subjective exercise intensity and dyspnea in cardiovascular patient populations. The 6-20 point Borg Scale will be administered immediately after the 6-Minute Walk Test, where participants rate their perceived level of exertion ranging from 6 (no exertion at all) to 20 (maximal exertion). Lower scores indicate less perceived physical exertion and better exercise tolerance. The change in Borg RPE score from baseline to the end of treatment will be calculated as the primary efficacy endpoint. | Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks，52weeks (end of follow-up) |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Concentration at 52 Weeks | N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-validated circulating biomarker for cardiac wall stress, ventricular dysfunction, and cardiovascular disease prognosis, widely used in the management of heart failure, acute coronary syndrome and other cardiovascular conditions. Fasting venous blood samples will be collected from participants at specified time points, and serum NT-proBNP concentration will be measured using a clinically validated quantitative assay (unit: picograms per milliliter, pg/mL). The change in NT-proBNP concentration from baseline to the end of treatment will be calculated as the primary efficacy endpoint: a greater reduction in NT-proBNP indicates alleviation of cardiac load and better therapeutic effect. For participants with heart failure, a reduction of ≥30% in NT-proBNP from baseline is generally recognized as a threshold of clinically meaningful improvement. |
Not provided
Inclusion Criteria:
1. Male or female participants aged between 18 and 75 years (inclusive) at the screening visit.
2. Diagnosed with pulmonary arterial hypertension (PAH) classified according to the *2021 Chinese Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension*, and belonging to one of the following subgroups:
Subgroup Ⅰ: Idiopathic pulmonary arterial hypertension (IPAH) under the category of arterial pulmonary hypertension
Subgroup Ⅱ: Pulmonary hypertension secondary to left heart disease (congenital heart disease) 3. World Health Organization (WHO) Functional Class III or IV symptoms at screening.
4. Meet all of the following hemodynamic criteria confirmed by right heart catheterization (RHC) at study screening: mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg.
5. Able to walk a minimum of 100 meters and a maximum of 440 meters during the 6-Minute Walk Test (6MWT) at the screening visit; in addition, participants must demonstrate stable baseline 6MWT performance between the screening visit and the randomization visit.
6. Participants with pulmonary hypertension who are either treatment-naïve or currently receiving treatment: for participants who have received prior treatment (defined as having used PAH-targeted therapeutic agents within 4 weeks before screening), mPAP ≥ 25 mmHg and PCWP ≤ 15 mmHg must be confirmed at the randomization visit.
7. Able to understand study procedures, willing to comply with study restrictions, and willing and able to provide written informed consent prior to the initiation of all study-related procedures.
Exclusion Criteria:
1. Meet any of the following criteria: 2. Diagnosed with Group 3 or Group 5 pulmonary hypertension (PH) according to the *2021 Chinese Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension*.
3. Echocardiogram within 6 months before screening indicates left ventricular ejection fraction (LVEF) ≤ 40%, or clinically significant ischemic mitral or aortic valve disease, or constrictive heart disease as judged by the investigator.
4. Presence of 3 or more of the following risk factors for left ventricular dysfunction:
Body mass index (BMI) ≥ 30 kg/m² at screening visit
History of essential hypertension
Diabetes mellitus of any type
History of significant coronary artery disease (CAD) confirmed by any of the following:
History of myocardial infarction
History of percutaneous coronary intervention (PCI)
Angiographic evidence of ≥ 50% stenosis in at least one major coronary artery
Positive cardiac stress imaging test
History of coronary artery bypass graft surgery (CABG)
History of chronic stable angina or unstable angina 5. Uncontrolled systemic arterial hypertension: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg at randomization visit (Day 1).
6. History of long QT syndrome or torsades de pointes ventricular tachycardia. 7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal (ULN) at screening visit.
8. Severe renal impairment: estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at screening calculated by the CKD-EPI formula.
9. Severe hepatic impairment (Child-Pugh Class C) at screening visit, with or without cirrhosis; patients receiving renal dialysis or with a history of renal transplantation.
10. Known coagulation defects, including: hereditary or acquired coagulation disorders (factor XII deficiency, factor XIII deficiency), reduced coagulation factor production due to acute or chronic liver disease, impaired coagulation efficiency caused by lupus anticoagulant, disseminated intravascular coagulation (DIC), or anticoagulant factor autoantibodies.
11. Evidence or history of major hemorrhage or intracranial hemorrhage. 12. History of increased intracranial pressure. 13. Pregnant or lactating women. 14. Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of any drug, including but not limited to: history of major gastrointestinal surgery deemed clinically significant by the investigator within 12 months before screening (e.g., gastrectomy, gastrointestinal stoma anastomosis, intestinal resection, gastric bypass surgery, gastroenterostomy, or gastric banding), current active inflammatory bowel disease, or history of active inflammatory bowel disease.
15. Any surgical or medical condition not specified in the protocol that, in the investigator's opinion, would expose the patient to higher risk due to study participation, or may prevent the patient from complying with study requirements or completing the trial period.
16. Patients who are unwilling or unable to safely discontinue current pulmonary arterial hypertension (PAH)-targeted medications during the study as required by the protocol.
17. History of any contraindication or hypersensitivity reaction to any study drug or drugs with similar chemical structures.
18. History of active substance abuse (including alcohol) within the past 1 year, or patients considered potentially unreliable by the investigator.
19. Personnel directly involved in the conduct of this clinical study.
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xuyu He, MD, PhD | Contact | 86136322737312 | hexuyu97@126.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangdong Provincial People's Hospital | Recruiting | Guangzhou | Guagdong | 515000 | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Standard Pulmonary Arterial Hypertension (PAH)-Targeted Therapy Alone | Drug | Control Group Intervention: Participants in this group receive standard pulmonary arterial hypertension (PAH)-targeted therapy alone, without additional Qishen Yiqi Dropping Pills. The targeted therapy regimen complies with the *2021 Chinese Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension*, including one or more clinically approved PAH-targeted agents (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or soluble guanylate cyclase stimulators) at standard recommended doses. The regimen is consistent with the participants' stable pre-enrollment treatment plan, or initiated per the protocol-specified dosing schedule, with no dose adjustment allowed during the study period unless required for safety reasons. The total treatment duration is 26 weeks, identical to the experimental group. |
|
| Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks， 52weeks (end of follow-up) |
| Change from Baseline in WHO (NYHA) Functional Classification of Cardiac Status at 52 Weeks | The World Health Organization (WHO) recommended New York Heart Association (NYHA) Functional Classification is a widely used, validated clinical scale to assess the severity of heart failure and functional status in patients with cardiovascular disease. The classification grades cardiac function based on the degree of dyspnea and fatigue experienced during daily activities, ranging from Grade I to Grade IV:
T | Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks，52weeks (end of follow-up) |
| Change from Baseline in Systolic Pulmonary Arterial Pressure (sPAP) Measured by Echocardiography at 12 Weeks | Systolic Pulmonary Arterial Pressure (sPAP) is a key hemodynamic parameter reflecting the pressure in the pulmonary artery during cardiac systole, widely used for the diagnosis, severity assessment and prognosis evaluation of pulmonary hypertension, left heart failure, valvular heart disease and other cardiovascular conditions. sPAP will be measured by transthoracic echocardiography performed by qualified sonographers at specified time points, calculated based on the tricuspid regurgitation jet velocity using the simplified Bernoulli equation, with measurement unit in millimeters of mercury (mmHg). The change in sPAP concentration from baseline to the end of treatment will be calculated as the primary efficacy endpoint: a greater reduction in sPAP indicates alleviation of pulmonary vascular resistance and right ventricular load, as well as better therapeutic effect. In patients with left heart disease related pulmonary hypertension, a reduction of ≥10 mmHg in sPAP from baseline is gen | Baseline, 1 weeks, 8 weeks, 26 weeks，40weeks，52weeks (end of follow-up) |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) in Participants Receiving Qishen Yiqi Dropping Pills Combined with Targeted Therapy versus Targeted Therapy Alone | Baseline (within 7 days before treatment initiation), every 2 weeks during treatment, at the end of treatment (12 weeks), and 30 days after the last dose of study treatment (safety follow-up) |
| ID | Term |
|---|---|
| D065627 | Familial Primary Pulmonary Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C060424 | hydralazine 4-anisaldehyde hydrazone |
Not provided
Not provided
Not provided