Hypertension
Conditions
Brief summary
This is a multicenter, randomized, double-blind, parallel-controlled Phase IV clinical trial designed to evaluate the efficacy and safety of sitogilun malate tablets in combination with amlodipine besylate tablets in patients with mild to moderate essential hypertension and risk of early kidney damage. Approximately 456 eligible participants will be randomized in a 1:1:1 ratio to receive sitogilun malate plus amlodipine, allisartan isoproxil plus amlodipine, or placebo plus amlodipine for 8 weeks. The primary efficacy outcome is the change from baseline in mean sitting diastolic blood pressure (msDBP) at Week 8. Secondary efficacy outcomes include changes in mean sitting systolic blood pressure (msSBP), blood pressure response and control rates, ambulatory blood pressure parameters, and urinary albumin-to-creatinine ratio (UACR). Safety will also be evaluated throughout the study.
Interventions
DRUGSitogilun Malate
Sitogilun malate tablets, 100 mg orally once daily for 8 weeks.
Allisartan isoproxil tablets, 240 mg orally once daily for 8 weeks.
Amlodipine besylate tablets, 5 mg orally once daily for 8 weeks.
DRUGSitogilun Malate Placebo
Matching placebo for sitogilun malate, two tablets orally once daily for 8 weeks.
DRUGAllisartan Isoproxil Placebo
Matching placebo for allisartan isoproxil, one tablet orally once daily for 8 weeks.
Sponsors
Shanghai Jiao Tong University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
A double-dummy design will be used to maintain blinding. Participants will receive active sitogilun malate or matching placebo and active allisartan isoproxil or matching placebo, as applicable to the assigned treatment group.
Intervention model description
Eligible participants will be randomized in a 1:1:1 ratio to three parallel treatment groups to receive sitogilun malate plus amlodipine, allisartan isoproxil plus amlodipine, or placebo plus amlodipine for 8 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥18 years. 2. Male or female. 3. Diagnosed with mild to moderate essential hypertension (Grade 1 or Grade 2 hypertension). At both screening and prior to randomization, seated diastolic blood pressure (DBP) must be 90-109 mmHg, with or without seated systolic blood pressure (SBP) of 140-179 mmHg. 4. Urinary albumin-to-creatinine ratio (UACR) of 15-30 mg/g, inclusive, at both screening and prior to randomization. 5. Fully understands the study and voluntarily agrees to participate and provides written informed consent.
Exclusion criteria
1. Secondary hypertension, as determined by the investigator. 2. Severe cardiac disease within 6 months prior to screening, including chronic congestive heart failure (NYHA Class III or IV), acute myocardial infarction, unstable angina, cardiogenic shock, arrhythmias requiring treatment, valvular heart disease, hypertrophic cardiomyopathy, or rheumatic heart disease. 3. Severe cerebrovascular disease or events within 6 months prior to screening, including hypertensive encephalopathy, cerebrovascular injury, cerebral hemorrhage, or transient ischemic attack. 4. History of Takayasu arteritis, aortic aneurysm, aortic dissection, unilateral or bilateral renal artery stenosis, or severe subclavian artery stenosis. 5. Diagnosed or suspected primary glomerulonephritis, renal involvement due to autoimmune disease, diabetic kidney disease, polycystic kidney disease, or other diseases that may cause an elevated UACR at screening. 6. Laboratory abnormalities at screening, including alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>2 × the upper limit of normal (ULN), estimated glomerular filtration rate (eGFR) \<30 mL/min, or hemoglobin \<90 g/L. 7. Serum potassium \>5.5 mmol/L at screening. 8. Poorly controlled diabetes mellitus, defined as fasting blood glucose \>11 mmol/L at screening. 9. Current or previous diagnosis of hyperthyroidism or hypothyroidism, except for resolved thyroid dysfunction or subclinical hyperthyroidism/hypothyroidism. 10. History of gastrointestinal surgery that may significantly alter drug absorption, distribution, metabolism, or excretion. 11. Major surgery within 3 months prior to screening or planned major surgery during the study. 12. History of malignancy within 5 years prior to screening, except adequately treated cervical carcinoma in situ, basal-cell or squamous-cell skin cancer, localized prostate cancer after curative surgery, or papillary thyroid carcinoma. 13. Planned use during the study of antihypertensive medications or other medications known to affect blood pressure, such as monoamine oxidase inhibitors, corticosteroids, nonsteroidal anti-inflammatory drugs, oral contraceptives, or antidepressants. 14. Abnormal daily sleep-wake schedule (e.g., reversal of the normal day-night schedule) that, in the investigator's judgment, may affect blood pressure. 15. Hypersensitivity to any study drug or its excipients, or a history of hypersensitivity to angiotensin II receptor blockers or calcium channel blockers. 16. History of drug abuse or alcohol abuse within 1 year prior to screening. 17. Participation as a study participant in another drug or medical device clinical trial within 1 month prior to screening. 18. Pregnant or breastfeeding women, or participants or their partners planning pregnancy during the study or within 6 months after completion of the study. 19. Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | Baseline to Week 8 | Mean sitting diastolic blood pressure (msDBP) will be measured in mmHg. The change from baseline to Week 8 will be calculated. A greater reduction in msDBP indicates a greater blood pressure-lowering effect. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 4 | Baseline to Week 4 |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 4 | Baseline to Week 4 |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8 | Baseline to Week 8 |
| Overall Blood Pressure Response Rate at Weeks 4 and 8 | Weeks 4 and 8 |
| Blood Pressure Control Rate at Weeks 4 and 8 | Weeks 4 and 8 |
| Change From Baseline in Ambulatory Blood Pressure Monitoring (ABPM) Parameters at Week 8 | Baseline to Week 8 |
| Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) at Week 8 | Baseline to Week 8 |
Countries
China
Contacts
CONTACTJi-guang Wang, MD, PhD
Outcome results
None listed