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

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 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

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