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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00775814
Recruitment Status : Completed
First Posted : October 20, 2008
Last Update Posted : August 8, 2012
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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.

Condition or disease Intervention/treatment Phase
Obesity Hypertension Drug: Candesartan and Hydrochlorothiazide Drug: Hydrochlorothiazide (HCT) Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized Trial to Investigate the Antihypertensive and Metabolic Effects of Candesartan in Insulin-resistant Obese Patients With a Hypertension Not Adequately Controlled by Previous ß-blocker or Calcium Channel Blocker
Study Start Date : October 2006
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Candesartan + Hydrochlorothiazide QD Drug: 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.

Active Comparator: Hydrochlorothiazide QD Drug: Hydrochlorothiazide (HCT)
Candesartan placebo-matching tablets and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 24 weeks.

Primary Outcome Measures :
  1. The change from Baseline in Blood pressure (mean reduction in Diastolic Blood Pressure measured at trough). [ Time Frame: End of Treatment ]

Secondary Outcome Measures :
  1. The change from Baseline in Adiponectin. [ Time Frame: At Final Visit. ]
  2. The change from Baseline in high sensitivity C-Reactive Protein. [ Time Frame: At Final Visit. ]
  3. The change from Baseline in Fasting Plasma Glucose. [ Time Frame: At Final Visit. ]
  4. The change from Baseline in Fasting Plasma Insulin. [ Time Frame: At Final Visit. ]
  5. The change from Baseline in Insulin Resistance (assessed by Homeostasis Model Assessment Insulin Resistance). [ Time Frame: At Final Visit. ]
  6. The change from Baseline in Lipid Parameters (total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides). [ Time Frame: At Final Visit. ]
  7. The change from Baseline in Fibrinogen. [ Time Frame: At Final Visit. ]
  8. The change from Baseline in Prospective Cardiovascular Münster risk score for the assessment of coronary heart disease. [ Time Frame: At Final Visit. ]
  9. The change from Baseline in 24-hour mean blood pressure as assessed by Ambulatory Blood Pressure Measurement. [ Time Frame: At Final Visit. ]
  10. The change from Baseline in Daytime and night-time mean blood pressure Ambulatory Blood Pressure Measurement. [ Time Frame: At Final Visit. ]
  11. The change from Baseline in Systolic Blood Pressure. [ Time Frame: End of Treatment. ]

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Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00775814

Bad Dürrheim, Baden-Württemberg, Germany
Balingen, Baden-Württemberg, Germany
Deggingen, Baden-Württemberg, Germany
Rottweil, Baden-Württemberg, Germany
Spaichingen, Baden-Württemberg, Germany
Ingolstadt, Bayern, Germany
München, Bayern, Germany
Passau, Bayern, Germany
Schauenburg, Hessen, Germany
Bocholt, Nordrhein-Westfalen, Germany
Essen, Nordrhein-Westfalen, Germany
Isselburg, Nordrhein-Westfalen, Germany
Köln, Nordrhein-Westfalen, Germany
Roetgen, Nordrhein-Westfalen, Germany
Troisdorf, Nordrhein-Westfalen, Germany
Wesseling, Nordrhein-Westfalen, Germany
Roedersheim-Gronau, Rheinland-Pfalz, Germany
Dresden, Sachsen, Germany
Freital, Sachsen, Germany
Machem, Sachsen, Germany
Markkleeberg, Sachsen, Germany
Wermsdorf, Sachsen, Germany
Bad Segeberg, Schleswig-Holstein, Germany
Berlin, Germany
Sponsors and Collaborators
Study Director: Medical Director Takeda Pharma Gmbh, Aachen (Germany)

Responsible Party: Takeda Identifier: NCT00775814     History of Changes
Other Study ID Numbers: BLO K025
2006-001998-25 ( EudraCT Number )
D-CAN-545 ( Other Identifier: Takeda ID )
U1111-1113-9336 ( Registry Identifier: WHO )
First Posted: October 20, 2008    Key Record Dates
Last Update Posted: August 8, 2012
Last Verified: August 2012

Keywords provided by Takeda:
Drug Therapy
Blood Pressure
Insulin, Resistant

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Candesartan cilexetil
Calcium Channel Blockers
Hypoglycemic Agents
Physiological Effects of Drugs
Antihypertensive Agents
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists