Back to resultsStudy to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease
Primary Purpose
Aortic Stenosis, Aortic Regurgitation, Hypertension
Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Amlodipine 5mg
Losartan
Losartan and Amlodipine
Amlodipine/Losartan/Chlorthalidone
current treatment
Sponsored by
About this trial
This is an interventional treatment trial for Aortic Stenosis focused on measuring Aortic Stenosis, Aortic Regurgitation, Hypertension, LVM, Left Ventricular Hypertrophy
Eligibility Criteria
Inclusion Criteria:
- Male or female aged ≥ 19 years and < 80 years
- Diagnosis of mild-moderate AS or mild-moderate AR
- 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
- Diagnosis of hypertension (SBP > 130 mmHg if being treated or SBP > 140 mmHg if being untreated)
- 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
- Voluntary written consent to taking part in the clinical study and willingness to comply with requirements of the study
Exclusion Criteria:
- History of a cardiac valve replacement surgery (replacement surgery of mitral valve, aortic valve or tricuspid valve)
- Accompanied by severe mitral regurgitation
- Admitted to needing a surgery by the current treatment guidelines
- Accompanied by symptoms such as angina pectoris, exertional dyspnea, syncope, etc.
- < 50% of left ventricular ejection fraction
- 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
- Pregnant or breastfeeding
- Symptomatic orthostatic hypotension
- Severe liver failure or renal failure (< 30 mL/min of creatinine clearance)
- Hereditary angioedema or history of angioedema at treatment with ACE inhibitors or angiotensin II receptor blockers
- Primary hyperaldosteronism
- Genetic problems such as galactose intolerance, Lapp Lapp lactase deficiency or glucose-galactose malabsorption
- Anuria
- Refractory hypokalemia
- Hyponatremia or hypercalcemia
- Symptomatic hyperuricemia (history of gout or uric acid lithiasis)
- Untreated Addison's disease
- Appropriately uncontrolled diabetes
- Congenital or incurable hypertension
- Diagnosis of severe cerebrovascular disorders (stroke, cerebral infarction, cerebral hemorrhage, etc.) within six months prior to the date of ICF obtainment
- Wasting disease, autoimmune disease or connective tissue disease
- Diagnosis of malignant tumor within five years prior to the date of ICF obtainment
- Administration of another investigational product within four weeks prior to the date of ICF obtainment
- For a patient who is taking anticoagulants and thrombolytic agents; considered difficult to keep a stable dosage/regimen by the investigator.
- Considered unsuitable to be a subject by the investigator
Sites / Locations
- 10 Institutions Including Asan Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
The intensive care group
The usual care group
Arm 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.
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.
Outcomes
Primary Outcome Measures
To evaluate changes from baseline in Left Ventricular Mass at 24M
To evaluate changes from baseline in Left Ventricular Mass at 24M
Secondary Outcome Measures
Changes from baseline in Left Ventricular global longitudinal strain at 24M
Changes from baseline in Left Ventricular global longitudinal strain at 24M
Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M
Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M
Changes from baseline in Left Ventricular volumes at 24M
Changes from baseline in Left Ventricular volumes at 24M
Rate of disease progression
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
To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M
To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M
Cumulative incidence rate for each visit time point
Cumulative incidence rate for each visit time point
- Death, Cardiovascular death, Heart Failure, Myocardial Infarction, Hospitalization, Aortic Valve Replacement
Changes from baseline in stroke volume index at 24M
Changes from baseline in stroke volume index at 24M
Changes from baseline in Left Ventricular ejection fraction at 24M
Changes from baseline in Left Ventricular ejection fraction at 24M
Full Information
NCT ID
NCT03666351
First Posted
August 20, 2018
Last Updated
September 13, 2022
Sponsor
Hanmi Pharmaceutical Company Limited
1. Study Identification
Unique Protocol Identification Number
NCT03666351
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
October 18, 2018 (Actual)
Primary Completion Date
July 25, 2022 (Actual)
Study Completion Date
July 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hanmi Pharmaceutical Company Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
Detailed Description
1.Primary objectives
- To evaluate changes from baseline in LVM at V5 (24M)
2.Secondary objectives
To evaluate changes from baseline in LV global longitudinal strain at V5 (24M)
To evaluate changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at V5 (24M)
To evaluate changes from baseline in LV volumes, a stroke volume index and LV ejection fraction at V5 (24M)
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)
To evaluate changes from baseline in blood pressure at V2(6M), V3(12M), V4(18M) and V5(24M)
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)
To evaluate outcomes of adverse events, physical examination, vital signs (pulse) and laboratory tests (hematological examination, blood biochemical examination, urine test and pregnancy test)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Stenosis, Aortic Regurgitation, Hypertension, LVM, Left Ventricular Hypertrophy
Keywords
Aortic Stenosis, Aortic Regurgitation, Hypertension, LVM, Left Ventricular Hypertrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A prospective, multicentre, randomized, open label, evaluator-blind study
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
The intensive care group
Arm Type
Experimental
Arm 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.
Arm Title
The usual care group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Amlodipine 5mg
Other Intervention Name(s)
Amodipin Tab.
Intervention Description
Amlodipine 5 mg
Intervention Type
Drug
Intervention Name(s)
Losartan
Other Intervention Name(s)
Osartan Tab. 50 mg
Intervention Description
Losartan Potassium 50 mg
Intervention Type
Drug
Intervention Name(s)
Losartan and Amlodipine
Other Intervention Name(s)
Amosartan Tab. 5/50 mg, Amosartan Tab. 5/100 mg
Intervention Description
Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg
Intervention Type
Drug
Intervention Name(s)
Amlodipine/Losartan/Chlorthalidone
Other Intervention Name(s)
Amosartan Plus Tab. 5/100/12.5 mg
Intervention Description
Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg
Intervention Type
Drug
Intervention Name(s)
current treatment
Intervention Description
treatment is done by maintaining the current treatment
Primary Outcome Measure Information:
Title
To evaluate changes from baseline in Left Ventricular Mass at 24M
Description
To evaluate changes from baseline in Left Ventricular Mass at 24M
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Changes from baseline in Left Ventricular global longitudinal strain at 24M
Description
Changes from baseline in Left Ventricular global longitudinal strain at 24M
Time Frame
24 months
Title
Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M
Description
Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M
Time Frame
24 months
Title
Changes from baseline in Left Ventricular volumes at 24M
Description
Changes from baseline in Left Ventricular volumes at 24M
Time Frame
24 months
Title
Rate of disease progression
Description
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
Time Frame
24 months
Title
To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M
Description
To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M
Time Frame
6 months, 12 months, 18 months, 24 months
Title
Cumulative incidence rate for each visit time point
Description
Cumulative incidence rate for each visit time point
- Death, Cardiovascular death, Heart Failure, Myocardial Infarction, Hospitalization, Aortic Valve Replacement
Time Frame
6 months, 12 months, 18 months, 24 months
Title
Changes from baseline in stroke volume index at 24M
Description
Changes from baseline in stroke volume index at 24M
Time Frame
24 months
Title
Changes from baseline in Left Ventricular ejection fraction at 24M
Description
Changes from baseline in Left Ventricular ejection fraction at 24M
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Occurrence and frequency of adverse events
Description
Occurrence and frequency of adverse events
Time Frame
6 months, 12 months, 18 months, 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female aged ≥ 19 years and < 80 years
Diagnosis of mild-moderate AS or mild-moderate AR
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
Diagnosis of hypertension (SBP > 130 mmHg if being treated or SBP > 140 mmHg if being untreated)
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
Voluntary written consent to taking part in the clinical study and willingness to comply with requirements of the study
Exclusion Criteria:
History of a cardiac valve replacement surgery (replacement surgery of mitral valve, aortic valve or tricuspid valve)
Accompanied by severe mitral regurgitation
Admitted to needing a surgery by the current treatment guidelines
Accompanied by symptoms such as angina pectoris, exertional dyspnea, syncope, etc.
< 50% of left ventricular ejection fraction
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
Pregnant or breastfeeding
Symptomatic orthostatic hypotension
Severe liver failure or renal failure (< 30 mL/min of creatinine clearance)
Hereditary angioedema or history of angioedema at treatment with ACE inhibitors or angiotensin II receptor blockers
Primary hyperaldosteronism
Genetic problems such as galactose intolerance, Lapp Lapp lactase deficiency or glucose-galactose malabsorption
Anuria
Refractory hypokalemia
Hyponatremia or hypercalcemia
Symptomatic hyperuricemia (history of gout or uric acid lithiasis)
Untreated Addison's disease
Appropriately uncontrolled diabetes
Congenital or incurable hypertension
Diagnosis of severe cerebrovascular disorders (stroke, cerebral infarction, cerebral hemorrhage, etc.) within six months prior to the date of ICF obtainment
Wasting disease, autoimmune disease or connective tissue disease
Diagnosis of malignant tumor within five years prior to the date of ICF obtainment
Administration of another investigational product within four weeks prior to the date of ICF obtainment
For a patient who is taking anticoagulants and thrombolytic agents; considered difficult to keep a stable dosage/regimen by the investigator.
Considered unsuitable to be a subject by the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Duk-Hyun Kang
Organizational Affiliation
10 institutions including Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
10 Institutions Including Asan Medical Center
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
De-identified individual participant data
Citations:
PubMed Identifier
36398903
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.
Results Reference
derived
PubMed Identifier
32905623
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.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease
We'll reach out to this number within 24 hrs