Aortic Stenosis, Aortic Regurgitation, Hypertension, LVM, Left Ventricular Hypertrophy
Conditions
Keywords
Aortic Stenosis, Aortic Regurgitation, Hypertension, LVM, Left Ventricular Hypertrophy
Brief summary
To compare changes in Left Ventricular Mass (LVM) depending on each blood pressure regulation between the intensive care group and the usual care group for patients with hypertension accompanied by aortic valve disease and evaluate an influence of blood pressure regulation on improvement of left ventricular hypertrophy and its safety
Detailed description
1.Primary objectives \- To evaluate changes from baseline in LVM at V5 (24M) 2.Secondary objectives 1. To evaluate changes from baseline in LV global longitudinal strain at V5 (24M) 2. To evaluate changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at V5 (24M) 3. To evaluate changes from baseline in LV volumes, a stroke volume index and LV ejection fraction at V5 (24M) 4. To evaluate a rate of disease progression * In case of Aortic stenosis (AS), to evaluate changes from baseline in Aortic Valve Area (AVA), Vmax, Mean Pressure Gradient (PG) and Valvulo-arterial impedance (Zva) at V5 (24M) * In case of Aortic regurgitation (AR), to evaluate changes from baseline in Vena contracta at V5 (24M) 5. To evaluate changes from baseline in blood pressure at V2(6M), V3(12M), V4(18M) and V5(24M) 6. To evaluate a cumulative incidence rate for each visit time point * Death, Cardiovascular(CV) death, Heart Failure(HF), Myocardial Infarction(MI), Hospitalization, Aortic Valve Replacement(AVR) 7. To evaluate outcomes of adverse events, physical examination, vital signs (pulse) and laboratory tests (hematological examination, blood biochemical examination, urine test and pregnancy test)
Interventions
DRUGAmlodipine 5mg
Amlodipine 5 mg
DRUGLosartan
Losartan Potassium 50 mg
Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
DRUGAmlodipine/Losartan/Chlorthalidone
Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg
treatment is done by maintaining the current treatment
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
A prospective, multicentre, randomized, open label, evaluator-blind study
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥ 19 years and \< 80 years 2. Diagnosis of mild-moderate AS or mild-moderate AR 3. Applicable to 2.0\ 3.9 m/s of aortic jet velocity for mild-moderate AS or to 0.2\ 0.6 cm of Vena contracta for mild-moderate AR 4. Diagnosis of hypertension (SBP \> 130 mmHg if being treated or SBP \> 140 mmHg if being untreated) 5. For females of childbearing potential; negative pregnancy test results during the screening period and prior to administration of the investigational product, and agreement on use of medically allowable contraceptive measures (condom, oral contraceptive pills, injectable or implantable contraceptives, intrauterine devices, birth control patches, etc.) during the study period 6. Voluntary written consent to taking part in the clinical study and willingness to comply with requirements of the study
Exclusion criteria
1. History of a cardiac valve replacement surgery (replacement surgery of mitral valve, aortic valve or tricuspid valve) 2. Accompanied by severe mitral regurgitation 3. Admitted to needing a surgery by the current treatment guidelines 4. Accompanied by symptoms such as angina pectoris, exertional dyspnea, syncope, etc. 5. \< 50% of left ventricular ejection fraction 6. History of hypersensitivity reaction to active ingredients of the investigational product (Amlodipine, Losartan and Chlorthalidone), dihydropyridine derivatives, thiazide drugs and other sulfonamide derivatives or their compositions 7. Pregnant or breastfeeding 8. Symptomatic orthostatic hypotension 9. Severe liver failure or renal failure (\< 30 mL/min of creatinine clearance) 10. Hereditary angioedema or history of angioedema at treatment with ACE inhibitors or angiotensin II receptor blockers 11. Primary hyperaldosteronism 12. Genetic problems such as galactose intolerance, Lapp Lapp lactase deficiency or glucose-galactose malabsorption 13. Anuria 14. Refractory hypokalemia 15. Hyponatremia or hypercalcemia 16. Symptomatic hyperuricemia (history of gout or uric acid lithiasis) 17. Untreated Addison's disease 18. Appropriately uncontrolled diabetes 19. Congenital or incurable hypertension 20. Diagnosis of severe cerebrovascular disorders (stroke, cerebral infarction, cerebral hemorrhage, etc.) within six months prior to the date of ICF obtainment 21. Wasting disease, autoimmune disease or connective tissue disease 22. Diagnosis of malignant tumor within five years prior to the date of ICF obtainment 23. Administration of another investigational product within four weeks prior to the date of ICF obtainment 24. For a patient who is taking anticoagulants and thrombolytic agents; considered difficult to keep a stable dosage/regimen by the investigator. 25. Considered unsuitable to be a subject by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate changes from baseline in Left Ventricular Mass at 24M | 24 months | To evaluate changes from baseline in Left Ventricular Mass at 24M |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in Left Ventricular global longitudinal strain at 24M | 24 months | Changes from baseline in Left Ventricular global longitudinal strain at 24M |
| Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M | 24 months | Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M |
| Changes from baseline in Left Ventricular volumes at 24M | 24 months | Changes from baseline in Left Ventricular volumes at 24M |
| Rate of disease progression | 24 months | * In case of Aortic Stenosis, to evaluate changes from baseline in Aortic Valve Area, tricuspid regurgitation velocity, Mean Pressure Gradient and Valvulo-arterial impedance at 24M * In case of Aortic Regurgitation, to evaluate changes from baseline in Vena contracta at 24M |
| Cumulative incidence rate for each visit time point | 6 months, 12 months, 18 months, 24 months | Cumulative incidence rate for each visit time point \- Death, Cardiovascular death, Heart Failure, Myocardial Infarction, Hospitalization, Aortic Valve Replacement |
| Changes from baseline in stroke volume index at 24M | 24 months | Changes from baseline in stroke volume index at 24M |
| Changes from baseline in Left Ventricular ejection fraction at 24M | 24 months | Changes from baseline in Left Ventricular ejection fraction at 24M |
| To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M | 6 months, 12 months, 18 months, 24 months | To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence and frequency of adverse events | 6 months, 12 months, 18 months, 24 months | Occurrence and frequency of adverse events |
Countries
South Korea
Outcome results
None listed