Amlodipine Versus Valsartan for Improvement of Diastolic Dysfunction Associated With Hypertension

NCT02973035 | Completed Phase 4

• 1 other identifier: YMC016
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 4

Brief Summary

Hypertensive patients are at increased risk of developing LV hypertrophy and myocardial fibrosis, which cause diastolic dysfunction. Because the activation of rennin-angiotensin-aldosterone system (RAAS) has been shown to induce LV hypertrophy and myocardial fibrosis, the RAAS may play a central role in the pathogenic process from hypertension to diastolic HF. Inhibitors of RAAS have been considered as a treatment option for these patients, and the angiotensin receptor blockers (ARB) have been of interest because they antagonize the effects of angiotensin II more completely. However, the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial reported that treatment with irbesartan did not reduce the risk of death or hospitalization for cardiovascular causes among 4,128 patients who had HF with a preserved LV ejection fraction. The degree of improvement of diastolic dysfunction was associated with the extent of systolic blood pressure reduction, whether a RAAS inhibitor or non-RAAS blood pressure lowering was used. Amlodipine is a potent and well-tolerated calcium channel blocker, and seems to be appropriate for achieving more aggressive systolic blood pressure target and improving diastolic dysfunction in hypertensive patients, because amlodipine is clinically very useful for controlling systolic blood pressure. Assessment of diastolic function by echocardiography will be helpful to determine whether addition of amlodipine or an ARB to standard therapy is more beneficial to hypertensive patients with diastolic dysfunction. The investigators hypothesize that amlodipine added to standard therapy will be superior to valsartan in improving diastolic dysfunction by lowering systolic blood pressure more effectively in hypertensive patients, and try to examine this hypothesis in a prospective, open-label, randomized comparison study using blinded echocardiographic evaluation for end point.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in the ratio of E velocity (Early mitral inflow velocity) to E' velocity (Early mitral annular velocity)

  24 weeks

Secondary Outcomes (5)

• Change in systolic blood pressure

  24 weeks

• Change in global LV longitudinal strain

  24 weeks

• Change in LV mass

  24 weeks

• Change in left atrial volume

  24 weeks

• Change in clinical composite

  24 weeks

Study Arms (2)

Amlodipine

EXPERIMENTAL

Amlodipine 2.5mg added to antihypertensive therapy

Drug: Amlodipine

Valsartan

EXPERIMENTAL

Valsartan 40mg added to antihypertensive therapy

Drug: Valsartan

Interventions

Amlodipine DRUG

Amlodipine

Valsartan DRUG

Valsartan

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Controlled hypertension: systolic BP \< 150 and diastolic BP \< 90 mmHg in persons aged 60 years or older, systolic BP \< 140 and diastolic BP \< 90 mmHg in persons 40 through 59 years according to the JNC 8th guideline
• Evidence of diastolic dysfunction showing E/E' \> 10
• The patient agrees to the study protocol and the schedule of clinical and echocardiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site

You may not qualify if:

• Unwillingness or inability to comply with the procedures described in this protocol
• Planned cardiac surgery or planned major non-cardiac surgery within the study period.
• Stroke or coronary revascularization in the past 6 months.
• Clinically significant pulmonary disease.
• Untreated hyperthyroidism, or hypothyroidism.
• A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.
• Female of child-bearing potential who do not use adequate contraception and women who are pregnant or breast-feeding
• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.
• LV ejection fraction \< 50%.
• Significant renal disease manifested by serum creatinine \> 2.5 mg/dL
• Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST \> 3 times upper limit of normal).
• History of intolerance to ARB or amlodipine.
• Hypertrophic or restrictive cardiomyopathy.
• Moderate or severe valvular disease.
• Constrictive pericarditis

Sponsors & Collaborators

• Asan Medical Center: lead
• Yuhan Corporation: collaborator

Study Sites (4)

Busan Baik Hospital

Busan, South Korea

Location

Busan University Hospital

Busan, South Korea

Location

Chungnam University Hospital

Daejeon, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Azoles; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Duk-Hyun Kang, M.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: December 1, 2016
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: January 14, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4)