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

Sponsor
Hanmi Pharmaceutical Company Limited (Industry)
Overall Status
Unknown status
CT.gov ID
NCT03666351
Collaborator
(none)
236
Enrollment
1
Location
2
Arms
41.4
Anticipated Duration (Months)
5.7
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 4

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)

  1. To evaluate changes from baseline in blood pressure at V2(6M), V3(12M), V4(18M) and V5(24M)

  2. 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)
  1. 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 Design

Study Type:
Interventional
Anticipated Enrollment :
236 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A prospective, multicentre, randomized, open label, evaluator-blind studyA prospective, multicentre, randomized, open label, evaluator-blind study
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 21, 2018
Anticipated Primary Completion Date :
Sep 30, 2021
Anticipated Study Completion Date :
Jan 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Amlodipine 5mg
Amlodipine 5 mg
Other Names:
  • Amodipin Tab.

    • Drug: Losartan
    Losartan Potassium 50 mg
    Other Names:
  • Osartan Tab. 50 mg

    • Drug: Losartan and Amlodipine
    Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
    Other Names:
  • Amosartan Tab. 5/50 mg, Amosartan Tab. 5/100 mg

    • Drug: Amlodipine/Losartan/Chlorthalidone
    Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg
    Other Names:
  • Amosartan Plus Tab. 5/100/12.5 mg

    		•
    Experimental: 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.

    Drug: Amlodipine 5mg
    Amlodipine 5 mg
    Other Names:
  • Amodipin Tab.

    • Drug: Losartan
    Losartan Potassium 50 mg
    Other Names:
  • Osartan Tab. 50 mg

    • Drug: Losartan and Amlodipine
    Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
    Other Names:
  • Amosartan Tab. 5/50 mg, Amosartan Tab. 5/100 mg

    • Drug: Amlodipine/Losartan/Chlorthalidone
    Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg
    Other Names:
  • Amosartan Plus Tab. 5/100/12.5 mg

    • Drug: current treatment
    treatment is done by maintaining the current treatment

    Outcome Measures

    Primary Outcome Measures

    1. To evaluate changes from baseline in Left Ventricular Mass at 24M [24 months]

      To evaluate changes from baseline in Left Ventricular Mass at 24M

    Secondary Outcome Measures

    1. Changes from baseline in Left Ventricular global longitudinal strain at 24M [24 months]

      Changes from baseline in Left Ventricular global longitudinal strain at 24M

    2. Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M [24 months]

      Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M

    3. Changes from baseline in Left Ventricular volumes at 24M [24 months]

      Changes from baseline in Left Ventricular volumes at 24M

    4. Rate of disease progression [24 months]

      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

    5. To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M [6 months, 12 months, 18 months, 24 months]

      To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M

    6. Cumulative incidence rate for each visit time point [6 months, 12 months, 18 months, 24 months]

      Cumulative incidence rate for each visit time point - Death, Cardiovascular death, Heart Failure, Myocardial Infarction, Hospitalization, Aortic Valve Replacement

    7. Changes from baseline in stroke volume index at 24M [24 months]

      Changes from baseline in stroke volume index at 24M

    8. Changes from baseline in Left Ventricular ejection fraction at 24M [24 months]

      Changes from baseline in Left Ventricular ejection fraction at 24M

    Other Outcome Measures

    1. Occurrence and frequency of adverse events [6 months, 12 months, 18 months, 24 months]

      Occurrence and frequency of adverse events

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 2.03.9 m/s of aortic jet velocity for mild-moderate AS or to 0.20.6 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 10 Institutions Including Asan Medical Center Seoul Korea, Republic of

    Sponsors and Collaborators

    • Hanmi Pharmaceutical Company Limited

    Investigators

    • Principal Investigator: Duk-Hyun Kang, 10 institutions including Asan Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hanmi Pharmaceutical Company Limited
    ClinicalTrials.gov Identifier:
    NCT03666351
    Other Study ID Numbers:
    • HM_AMO_401
    First Posted:
    Sep 11, 2018
    Last Update Posted:
    Sep 12, 2018
    Last Verified:
    Sep 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hanmi Pharmaceutical Company Limited
    Aortic Stenosis
    Aortic Regurgitation
    Hypertension
    LVM
    Left Ventricular Hypertrophy
    Additional relevant MeSH terms:
    Hypertension
    Aortic Valve Stenosis
    Hypertrophy, Left Ventricular
    Aortic Valve Insufficiency
    Hypertrophy
    Losartan
    Amlodipine
    Chlorthalidone

    Study Results

    No Results Posted as of Sep 12, 2018