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

Hypertension Clinical Trial

Official title:

A Prospective, Multicentre, Randomized, Open Label, Evaluator-Blind, Phase IV Study to Evaluate the Effect on Improvement of Left Ventricular Hypertrophy by the Control of Blood Pressure in Hypertension Patients With Aortic Valve Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03666351
• Other study ID #: HM_AMO_401
• Status: Completed
• Phase: Phase 4
• Start date: October 18, 2018
• Est. completion date: July 25, 2022

Study information

• Verified date: September 2022
• Source: Hanmi Pharmaceutical Company Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: July 25, 2022
• Est. primary completion date: July 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Aortic Regurgitation
• Aortic Stenosis
• Aortic Valve Insufficiency
• Aortic Valve Stenosis
• Hypertension
• Hypertrophy
• Hypertrophy, Left Ventricular
• Left Ventricular Hypertrophy
• LVM

Intervention

Drug:
• Amlodipine 5mg
Amlodipine 5 mg
• Losartan
Losartan Potassium 50 mg
• Losartan and Amlodipine
Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
• Amlodipine/Losartan/Chlorthalidone
Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg
• current treatment
treatment is done by maintaining the current treatment

Locations

Country	Name	City	State
Korea, Republic of	10 Institutions Including Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Hanmi Pharmaceutical Company Limited

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Occurrence and frequency of adverse events	Occurrence and frequency of adverse events	6 months, 12 months, 18 months, 24 months
Primary	To evaluate changes from baseline in Left Ventricular Mass at 24M	To evaluate changes from baseline in Left Ventricular Mass at 24M	24 months
Secondary	Changes from baseline in Left Ventricular global longitudinal strain at 24M	Changes from baseline in Left Ventricular global longitudinal strain at 24M	24 months
Secondary	Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M	Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M	24 months
Secondary	Changes from baseline in Left Ventricular volumes at 24M	Changes from baseline in Left Ventricular volumes at 24M	24 months
Secondary	Rate of disease progression	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	24 months
Secondary	To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M	To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M	6 months, 12 months, 18 months, 24 months
Secondary	Cumulative incidence rate for each visit time point	Cumulative incidence rate for each visit time point; - Death, Cardiovascular death, Heart Failure, Myocardial Infarction, Hospitalization, Aortic Valve Replacement	6 months, 12 months, 18 months, 24 months
Secondary	Changes from baseline in stroke volume index at 24M	Changes from baseline in stroke volume index at 24M	24 months
Secondary	Changes from baseline in Left Ventricular ejection fraction at 24M	Changes from baseline in Left Ventricular ejection fraction at 24M	24 months