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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: amlodipine/valsartan; Drug: hydrochlorothiazide/telmisartan

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Yonsei universty medical center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 15, 2013
• First Submitted That Met QC Criteria: March 24, 2013
• First Posted (Estimate): March 27, 2013

Study Record Updates

• Last Update Posted (Estimate): June 10, 2015
• Last Update Submitted That Met QC Criteria: June 9, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Valsartan; Hydrochlorothiazide; Telmisartan; Amlodipine, Valsartan Drug Combination; Telmisartan, hydrochlorothiazide drug combination
• Other Study ID Numbers: 4-2009-0077