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

NCT03666351 | Completed Phase 4

• 1 other identifier: HM_AMO_401
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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

Conditions

Aortic Stenosis; Aortic Regurgitation; Hypertension; LVM; Left Ventricular Hypertrophy

Keywords

Aortic Stenosis; Aortic Regurgitation; Hypertension; LVM; Left Ventricular Hypertrophy

Outcome Measures

Primary Outcomes (1)

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

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

  24 months

Secondary Outcomes (8)

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

  24 months

• 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 Left Ventricular volumes at 24M

  24 months

• Rate of disease progression

  24 months

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

  6 months, 12 months, 18 months, 24 months

Other Outcomes (1)

• Occurrence and frequency of adverse events

  6 months, 12 months, 18 months, 24 months

Study Arms (2)

The intensive care group

EXPERIMENTAL

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; Drug: Losartan; Drug: Losartan and Amlodipine; Drug: Amlodipine/Losartan/Chlorthalidone

The usual care group

EXPERIMENTAL

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; Drug: Losartan; Drug: Losartan and Amlodipine; Drug: Amlodipine/Losartan/Chlorthalidone; Drug: current treatment

Interventions

Amlodipine 5mg DRUG

Amlodipine 5 mg

Also known as: Amodipin Tab.

The intensive care group; The usual care group

Losartan DRUG

Losartan Potassium 50 mg

Also known as: Osartan Tab. 50 mg

The intensive care group; The usual care group

Losartan and Amlodipine DRUG

Amlodipine 5 mg/Losartan Potassium 50 mg, Amlodipine 5 mg/Losartan Potassium 100 mg

Also known as: Amosartan Tab. 5/50 mg, Amosartan Tab. 5/100 mg

The intensive care group; The usual care group

Amlodipine/Losartan/Chlorthalidone DRUG

Amlodipine 5 mg/Losartan Potassium 100 mg/Chlorthalidone 12.5 mg

Also known as: Amosartan Plus Tab. 5/100/12.5 mg

The intensive care group; The usual care group

current treatment DRUG

treatment is done by maintaining the current treatment

The usual care group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead

Study Sites (1)

10 Institutions Including Asan Medical Center

Seoul, South Korea

Location

Related Publications (3)

• Kim M, Choi JH, Kim HK, Kim HL, Shin SH, Jang JY, Park JH, Kim KH, Hong GR, Park SM, Lee SA, Kang DH. Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease. Am Heart J. 2024 Feb;268:45-52. doi: 10.1016/j.ahj.2023.11.012. Epub 2023 Nov 23.

  PMID: 38006908 DERIVED

• 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.

  PMID: 36398903 DERIVED

• 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.

  PMID: 32905623 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis; Aortic Valve Insufficiency; Hypertension; Hypertrophy, Left Ventricular

Interventions

Amlodipine; Losartan; amlodipine-losartan drug combination; Tablets

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Vascular Diseases; Cardiomegaly; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Tetrazoles; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Duk-Hyun Kang

  10 institutions including Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A prospective, multicentre, randomized, open label, evaluator-blind study

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: September 11, 2018
• Study Start: October 18, 2018
• Primary Completion: July 25, 2022
• Study Completion: July 25, 2022
• Last Updated: September 15, 2022

Record last verified: 2022-09

Locations

KR (1)