Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension.

NCT ID: NCT00775814

Last Updated: 2012-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2008-09-30

Brief Summary

The purpose of this study is to determine the efficacy of candesartan, once daily (QD), combined with hydrochlorothiazide to lower blood pressure in insulin-resistant, obese patients with hypertension.

Detailed Description

Abdominal obesity is a major risk factor for insulin resistance and the development of type 2 diabetes. It is associated with sodium retention, left ventricular hypertrophy and elevated markers of inflammation and is an important predictor of cardiovascular morbidity and mortality. Activation of the sympathetic nervous system and the renin angiotensin aldosterone system are both involved in the development of hypertension in obese individuals. Hypertension in obese individuals is often associated with dyslipidemia, hyperinsulinaemia and impaired glucose tolerance.

In order to decrease the cardiovascular risk of obese hypertensive patients, therapy should not only be directed to lowering blood pressure values but also to improvement of their metabolic situation. As it is possible that antihypertensive treatment based on an angiotensin receptor antagonist (like candesartan) might be superior to beta-blocker or calcium channel blocker therapy in preventing diabetes, a combination of candesartan with already existing insufficiently effective beta-blocker or calcium channel blocker therapy will be used in this study.

Conditions

Obesity; Hypertension

Keywords

Hypertension; Drug Therapy; Blood Pressure; Insulin, Resistant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Candesartan + Hydrochlorothiazide QD

Group Type: EXPERIMENTAL

Candesartan and Hydrochlorothiazide

Intervention Type: DRUG

Candesartan 8 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for 2 weeks; increased to Candesartan 16 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 24 weeks.

Hydrochlorothiazide QD

Group Type: ACTIVE_COMPARATOR

Hydrochlorothiazide (HCT)

Intervention Type: DRUG

Candesartan placebo-matching tablets and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 24 weeks.

Interventions

Candesartan and Hydrochlorothiazide

Candesartan 8 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for 2 weeks; increased to Candesartan 16 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Hydrochlorothiazide (HCT)

Candesartan placebo-matching tablets and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

BLOPRESS PLUS®

Eligibility Criteria

Inclusion Criteria

• Has an Abdominal obesity with a waist circumference greater than 102 cm (men) and greater than 88 cm (women).
• Has a body mass index greater than 30 kg/m^2.
• Has hypertension not adequately controlled (seated diastolic blood pressure greater than 95 mmHg and less than or equal to 110 mmHg as median value of three readings) by monotherapy with either beta-blocker or calcium channel blocker.
• Has a Homeostasis Model Assessment Insulin Resistance index greater than 3.99.
• Has hyperlipidemia with fasting levels for total cholesterol greater than 250 mg/dL (6.45 mmol/L) or low-density lipoprotein cholesterol greater than 160 mg/dL (4.13 mmol/L) or triglycerides greater than 250 mg/dL (2.82 mmol/L).

Exclusion Criteria

• Existing Hydrochlorothiazide therapy at start of study.
• Diabetes mellitus type 1 or 2 [known or newly detected (Screening: fasting plasma glucose greater than 7.0 mmol/L)].
• Chronic renal impairment or S-creatinine greater than or equal to 1.8 mg/dL.
• Presence of single kidney or state after kidney transplantation or known bilateral renal artery stenosis or interventional treatment for renal artery stenosis in the last year.
• Hyperkalemia (potassium greater than 5.5 mmol/L).
• Known electrolyte imbalance, e.g. hypocalcaemia or hypokalemia resistant to treatment.
• Nephrotic syndrome.
• Thyroid dysfunction.
• Primary or secondary hyperaldosteronism.
• Cushing syndrome.
• Known or suspected familial hypercholesterolemia.
• Severe hepatic impairment (cholestasis (bilirubin greater than 2.0 mg/dL) or alanine aminotransferase and/or aspartate aminotransferase greater than 3 times the upper limit of normal and/or γ-glutamyl transpeptidase greater than 5 times the upper limit of normal).
• History of chronic heart failure.
• History of overt coronary heart disease.
• History of silent myocardial infarction.
• Hemodynamically relevant stenosis of the mitral and/or aortic valve.
• History of stroke.
• Stage 3 hypertension (systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg).
• Angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy in the previous 4 weeks.
• Lipid-lowering therapy with cholesterol synthesis enzyme inhibitors or anticipated initiation of such a therapy.
• History of autoimmune disease.
• History of cancer in the last 5 years or wasting disease.
• Intake of prohibited concomitant medication.
• Has known hypersensitivity/allergy to the study drugs.
• Has drug addiction and/or extensive use of alcohol.
• Psychological and/or emotional problems which would render the informed consent invalid or limit the ability of the patient to comply with the study requirements.
• Participation in a clinical investigation within 30 days prior to enrolment in this trial.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda Pharma Gmbh, Aachen (Germany)

Locations

Bad Dürrheim, Baden-Wurttemberg, Germany

Balingen, Baden-Wurttemberg, Germany

Deggingen, Baden-Wurttemberg, Germany

Rottweil, Baden-Wurttemberg, Germany

Spaichingen, Baden-Wurttemberg, Germany

Ingolstadt, Bavaria, Germany

München, Bavaria, Germany

Passau, Bavaria, Germany

Schauenburg, Hesse, Germany

Bocholt, North Rhine-Westphalia, Germany

Cologne, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Isselburg, North Rhine-Westphalia, Germany

Roetgen, North Rhine-Westphalia, Germany

Troisdorf, North Rhine-Westphalia, Germany

Wesseling, North Rhine-Westphalia, Germany

Rödersheim-Gronau, Rhineland-Palatinate, Germany

Dresden, Saxony, Germany

Freital, Saxony, Germany

Machem, Saxony, Germany

Markkleeberg, Saxony, Germany

Wermsdorf, Saxony, Germany

Bad Segeberg, Schleswig-Holstein, Germany

Berlin, State of Berlin, Germany

Countries

Germany

Other Identifiers

2006-001998-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-CAN-545

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1113-9336

Identifier Type: REGISTRY

Identifier Source: secondary_id

BLO K025

Identifier Type: -

Identifier Source: org_study_id