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

NCT ID: NCT03666351

Last Updated: 2022-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-18
• Study Completion Date: 2022-07-25

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)

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

The intensive care group

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.

Group Type: EXPERIMENTAL

Amlodipine 5mg

Intervention Type: DRUG

Amlodipine 5 mg

Losartan

Intervention Type: DRUG

Losartan Potassium 50 mg

Losartan and Amlodipine

Intervention Type: DRUG

Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg

Amlodipine/Losartan/Chlorthalidone

Intervention Type: DRUG

Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg

The usual care group

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.

Group Type: EXPERIMENTAL

Amlodipine 5mg

Intervention Type: DRUG

Amlodipine 5 mg

Losartan

Intervention Type: DRUG

Losartan Potassium 50 mg

Losartan and Amlodipine

Intervention Type: DRUG

Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg

Amlodipine/Losartan/Chlorthalidone

Intervention Type: DRUG

Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg

current treatment

Intervention Type: DRUG

treatment is done by maintaining the current treatment

Interventions

Amlodipine 5mg

Amlodipine 5 mg

Intervention Type: DRUG

Losartan

Losartan Potassium 50 mg

Intervention Type: DRUG

Losartan and Amlodipine

Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg

Intervention Type: DRUG

Amlodipine/Losartan/Chlorthalidone

Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg

Intervention Type: DRUG

current treatment

treatment is done by maintaining the current treatment

Intervention Type: DRUG

Other Intervention Names

Amodipin Tab.; Osartan Tab. 50 mg; Amosartan Tab. 5/50 mg, Amosartan Tab. 5/100 mg; Amosartan Plus Tab. 5/100/12.5 mg

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hanmi Pharmaceutical Company Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Duk-Hyun Kang

Role: PRINCIPAL_INVESTIGATOR

10 institutions including Asan Medical Center

Locations

10 Institutions Including Asan Medical Center

Seoul, , South Korea

Countries

South Korea

References

Kim M, Choi JH, Kim HK, Kim HL, Shin SH, Jang JY, Park JH, Kim KH, Hong GR, Park SM, Lee SA, Kang DH. Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease. Am Heart J. 2024 Feb;268:45-52. doi: 10.1016/j.ahj.2023.11.012. Epub 2023 Nov 23.

Reference Type: DERIVED

PMID: 38006908 (View on PubMed)

Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.

Reference Type: DERIVED

PMID: 36398903 (View on PubMed)

Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.

Reference Type: DERIVED

PMID: 32905623 (View on PubMed)

Other Identifiers

HM_AMO_401

Identifier Type: -

Identifier Source: org_study_id