Brief Title
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
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)
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
To evaluate changes from baseline in Left Ventricular Mass at 24M
Secondary Outcome
Changes from baseline in Left Ventricular global longitudinal strain at 24M
Condition
Aortic Stenosis
Intervention
Amlodipine 5mg
Study Arms / Comparison Groups
The intensive care 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
236
Start Date
August 21, 2018
Completion Date
January 31, 2022
Primary Completion Date
September 30, 2021
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
Gender
All
Ages
19 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Duk-Hyun Kang, +821040984928, [email protected]
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT03666351
Organization ID
HM_AMO_401
Responsible Party
Sponsor
Study Sponsor
Hanmi Pharmaceutical Company Limited
Study Sponsor
Duk-Hyun Kang, Principal Investigator, 10 institutions including Asan Medical Center
Verification Date
September 2018