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

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ClinicalTrials.gov Identifier: NCT03666351
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
Hanmi Pharmaceutical Company Limited

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
Aortic Stenosis Aortic Regurgitation Hypertension LVM Left Ventricular Hypertrophy Drug: Amlodipine 5mg Drug: Losartan Drug: Losartan and Amlodipine Drug: Amlodipine/Losartan/Chlorthalidone Drug: current treatment 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)
  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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 236 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A 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 : August 21, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : January 31, 2022


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 Name: Amodipin Tab.

Drug: Losartan
Losartan Potassium 50 mg
Other Name: Osartan Tab. 50 mg

Drug: Losartan and Amlodipine
Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
Other Name: 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 Name: 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 Name: Amodipin Tab.

Drug: Losartan
Losartan Potassium 50 mg
Other Name: Osartan Tab. 50 mg

Drug: Losartan and Amlodipine
Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
Other Name: 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 Name: Amosartan Plus Tab. 5/100/12.5 mg

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




Primary Outcome Measures :
  1. To evaluate changes from baseline in Left Ventricular Mass at 24M [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 24 months ]
    Changes from baseline in Left Ventricular volumes at 24M

  4. Rate of disease progression [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 24 months ]
    Changes from baseline in stroke volume index at 24M

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


Other Outcome Measures:
  1. Occurrence and frequency of adverse events [ Time Frame: 6 months, 12 months, 18 months, 24 months ]
    Occurrence and frequency of adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03666351


Contacts
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Contact: Jong-Hwan Jeon +821040984928 jonghwan06@hanmi.co.kr

Locations
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Korea, Republic of
10 Institutions Including Asan Medical Center Recruiting
Seoul, Korea, Republic of
Contact: kang         
Sponsors and Collaborators
Hanmi Pharmaceutical Company Limited
Investigators
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Principal Investigator: Duk-Hyun Kang 10 institutions including Asan Medical Center

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Responsible Party: Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier: NCT03666351     History of Changes
Other Study ID Numbers: HM_AMO_401
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified individual participant data

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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:
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Hypertension
Aortic Valve Stenosis
Hypertrophy, Left Ventricular
Aortic Valve Insufficiency
Hypertrophy
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Ventricular Outflow Obstruction
Cardiomegaly
Losartan
Amlodipine
Chlorthalidone
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors