Clinical trial NCT03666351: Study to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aortic Stenosis
Aortic Regurgitation
Hypertension
LVM
Left Ventricular Hypertrophy
Keywords: Aortic Stenosis
Aortic Regurgitation
Hypertension
LVM
Left Ventricular Hypertrophy
Lead sponsor: Hanmi Pharmaceutical Company Limited
Sponsor class: INDUSTRY
First posted: 2018-09-11
Enrollment: 128
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, multicentre, randomized, open label, evaluator-blind study
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: To evaluate changes from baseline in Left Ventricular Mass at 24M
timeFrame: 24 months
Secondary outcomes:
measure: Changes from baseline in Left Ventricular global longitudinal strain at 24M
timeFrame: 24 months
measure: Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M
timeFrame: 24 months
measure: Changes from baseline in Left Ventricular volumes at 24M
timeFrame: 24 months
measure: Rate of disease progression
timeFrame: 24 months
measure: To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M
timeFrame: 6 months, 12 months, 18 months, 24 months
measure: Cumulative incidence rate for each visit time point
timeFrame: 6 months, 12 months, 18 months, 24 months
measure: Changes from baseline in stroke volume index at 24M
timeFrame: 24 months
measure: Changes from baseline in Left Ventricular ejection fraction at 24M
timeFrame: 24 months
Other outcomes:
measure: Occurrence and frequency of adverse events
timeFrame: 6 months, 12 months, 18 months, 24 months
Locations:
city: Seoul
country: Korea, Republic of
facility: 10 Institutions Including Asan Medical Center
Study officials:
affiliation: 10 institutions including Asan Medical Center
name: Duk-Hyun Kang
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.