Hypertension
Conditions
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.
Interventions
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.
DRUGhydrochlorothiazide/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.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
Countries
South Korea
Outcome results
None listed