Study to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease

Hanmi Pharmaceutical

Status and phase: Completed; Phase 4

Conditions: Hypertension; Aortic Regurgitation; Left Ventricular Hypertrophy; LVM; Aortic Stenosis

Treatments: Drug: Amlodipine/Losartan/Chlorthalidone; Drug: Losartan; Drug: Losartan and Amlodipine; Drug: Amlodipine 5mg; Drug: current treatment

Study type: Interventional

Funder types: Industry

Identifiers

NCT03666351

HM_AMO_401

Details and patient eligibility

About

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

Full 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)

Enrollment: 128 patients

Sex: All

Ages: 19 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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128 participants in 2 patient groups

The intensive care group

Experimental group

Description:

The intensive care group is targeted at ≤ 130 mmHg of systolic blood pressure, and treatment is done by changing the current treatment to the investigational product. In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -\> Losartan and Amlodipine 5/50 mg -\> Losartan and Amlodipine 5/100 mg -\> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.

Treatment:

Drug: Losartan and Amlodipine

Drug: Amlodipine 5mg

Drug: Losartan

Drug: Amlodipine/Losartan/Chlorthalidone

The usual care group

Experimental group

Description:

The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product. In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -\> Losartan and Amlodipine 5/50 mg -\> Losartan and Amlodipine 5/100 mg -\> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.

Treatment:

Drug: Losartan and Amlodipine

Drug: Amlodipine 5mg

Drug: Losartan

Drug: current treatment

Drug: Amlodipine/Losartan/Chlorthalidone