Randomized, Open Labeled Clinical Trial to Compare the Effectiveness of Amlodipine/Valsartan vs Hydrochlorothiazide/Telmisartan on Glucose Tolerance in Patients With Hypertension With Metabolic Syndrome

Sponsor

Yonsei University (Other)

Overall Status

Completed

CT.gov ID

NCT01819220

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recent studies have demonstrated that RAS inhibitors/calcium channel blockers are superior to RAS inhibitors/diuretics for reducing cardiovascular outcomes in hypertension. As such, RAS inhibitors/calcium channel blockers are recommended as first line combination treatment for hypertension. However, the mechanism for the superior efficacy of RAS inhibitors/calcium channel blockers are not well defined. This study will compare the efficacy of RAS inhibitors/calcium channel blockers vs RAS inhibitors/diuretics in terms of glucose tolerance and insulin resistance in hypertensive patients with metabolic syndrome. The primary endpoint will be that RAS inhibitors/calcium channel blockers will be more efficacious in reducing 2hour post prandial glucose compared to RAS inhibitors/diuretics.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: amlodipine/valsartan Drug: hydrochlorothiazide/telmisartan	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: amlodipine/valsartan	Drug: amlodipine/valsartan This is a phase IV clinical study. The study is a 24 week, prospective, randomized open labeled multicenter study to compare the efficacy of amlodipine/valsartan combination vs telmisartan/hydrochlorothiazide combination in reducing post prandial sugar. The study will be performed in hypertensive patients with metabolic syndrome. Active group: Starting dose of amlodipine 5mg/ valsartan 80mg comparator group: Telmisartan 40mg/hydrochlorothiazide 12.5mg When the blood pressure is above the target goal of 140/90mmHg, up titration to amlodipine 5/valsartan 160 and/or telmisartan 80/hydrochlorothiazide 12.5mg is allowed. When the blood pressure is above 140/90mmhg at the 12th week, addition of doxazosin 4mg is allowed. Other Names: Starting dose of amlodipine 5mg/ valsartan 80mg
Experimental: hydrochlorothiazide/telmisartan	Drug: hydrochlorothiazide/telmisartan When the blood pressure is above the target goal of 140/90mmHg, uptitration to amlodipine 5/valsartan 160 and/or telmisartan 80/hydrochlorothiazide 12.5mg is allowed. When the blood pressure is above 140/90mmhg at the 12th week, addition of doxazosin 4mg is allowed. Other Names: Telmisartan 40mg/hydrochlorothiazide 12.5mg

Arm

Intervention/Treatment

Active Comparator: amlodipine/valsartan

Drug: amlodipine/valsartan

This is a phase IV clinical study. The study is a 24 week, prospective, randomized open labeled multicenter study to compare the efficacy of amlodipine/valsartan combination vs telmisartan/hydrochlorothiazide combination in reducing post prandial sugar. The study will be performed in hypertensive patients with metabolic syndrome. Active group: Starting dose of amlodipine 5mg/ valsartan 80mg comparator group: Telmisartan 40mg/hydrochlorothiazide 12.5mg When the blood pressure is above the target goal of 140/90mmHg, up titration to amlodipine 5/valsartan 160 and/or telmisartan 80/hydrochlorothiazide 12.5mg is allowed. When the blood pressure is above 140/90mmhg at the 12th week, addition of doxazosin 4mg is allowed.

Other Names:

Starting dose of amlodipine 5mg/ valsartan 80mg

Experimental: hydrochlorothiazide/telmisartan

Drug: hydrochlorothiazide/telmisartan

When the blood pressure is above the target goal of 140/90mmHg, uptitration to amlodipine 5/valsartan 160 and/or telmisartan 80/hydrochlorothiazide 12.5mg is allowed. When the blood pressure is above 140/90mmhg at the 12th week, addition of doxazosin 4mg is allowed.

Other Names:

Telmisartan 40mg/hydrochlorothiazide 12.5mg

Outcome Measures

Primary Outcome Measures

To assess the glucose change [To assess the change from baseline (week 0) to study endpoint (week 24) on 2hr-post-prandial plasma glucose level using oral glucose tolerance test (75-g OGTT)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

consent to the study
Male or Female ≥ 20 years
Patients taking less than 1 antihypertensive medications or not taking antihypertensive medications. Hypertension defined at the screening visit as follows): 140mmHg < MSSBP or MSDBP > 90mmHg at screening
Hypertensive patients with non diabetic metabolic syndrome will be enrolled. Metabolic syndrome is defined according to NCEP guideline. (3 or more than) ① Abdominal obesity: Waist circumference M ≥ 90cm, F ≥ 80cm

② Hypertriglyceridaemia: Triglycerides ≥ 150mg/dL

③ Low HDL cholesterol Men: HDL cholesterol ≤ 40mg/dL Women: HDL cholesterol ≤ 50mg/dL

④ Elevated blood pressure (systolic blood pressure ≥ 130 mmHg and diastolic blood pressure ≥ 85 mmHg, or current use of antihypertensive drugs)

⑤ Impaired fasting glucose: fasting plasma glucose ≥ 100 mg/dL

Patient not taking statin medication and if the patient had ate statin medication the last duration must be before 3 months.

Exclusion Criteria:

• Women of child-bearing potential without a contraceptive measure
(Pregnant or nursing women
Known or suspected contraindications: history of allergy or hypersensitivity
History of clinically significant allergies including asthma and/or multiple drug allergies
Patients taking more than 2 antihypertensive medications
Patient taking statin medication and taking statin within 3 months
MSSBP > 180 mmHg or MSDBP > 110 mmHg at any time during the study
Evidence of a secondary form of hypertension)
History of hypertensive encephalopathy, cerebrovascular accident, transient ischemic attack, myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) for 12 months prior to Visit 1
History of heart failure Grade II - IV according to the NYHA classification
Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia
Concomitant unstable angina pectoris
Clinically significant valvular heart disease
Patients with Type 1 or Type 2 diabetes mellitus
Evidence of hepatic disease as determined by one of the following: AST or ALT values ≥ 3 x UNL, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt
Evidence of renal impairment as determined by one of the following: serum creatinine >2mg/dL , history of dialysis, or history of nephrotic syndrome
Protein in U/A values 2+ ≤
Serum potassium values < 3.2 or > 5.2 mmol/L
History of malignancy of any organ system within the past 5 years, treated or untreated, including leukemia and lymphoma, as further defined in the full protocol
Chronic use of NSAIDs
Use of cyclooxygenase-2 inhibitors (COX-2 inhibitors
Use of niacin > 100 mg/d
Use of loop diuretics
Use of statin shorter than 3 months
Inability to discontinue prior antihypertensive drugs as specified in the full protocol
persons directly involved in the execution of this protocol
Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values
Any severe, life-threatening disease within the past five years