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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00775814
First received: October 16, 2008
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Obesity
Hypertension
Drug: Candesartan and Hydrochlorothiazide
Drug: Hydrochlorothiazide (HCT)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • The change from Baseline in Blood pressure (mean reduction in Diastolic Blood Pressure measured at trough). [ Time Frame: End of Treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change from Baseline in Adiponectin. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in high sensitivity C-Reactive Protein. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Fasting Plasma Glucose. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Fasting Plasma Insulin. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Insulin Resistance (assessed by Homeostasis Model Assessment Insulin Resistance). [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Lipid Parameters (total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides). [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Fibrinogen. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Prospective Cardiovascular Münster risk score for the assessment of coronary heart disease. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in 24-hour mean blood pressure as assessed by Ambulatory Blood Pressure Measurement. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Daytime and night-time mean blood pressure Ambulatory Blood Pressure Measurement. [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • The change from Baseline in Systolic Blood Pressure. [ Time Frame: End of Treatment. ] [ Designated as safety issue: No ]

Enrollment: 188
Study Start Date: October 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: BLOPRESS PLUS®
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.

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.

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775814

Locations
Germany
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
Takeda
Investigators
Study Director: Medical Director Takeda Pharma Gmbh, Aachen (Germany)
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00775814     History of Changes
Other Study ID Numbers: BLO K025, 2006-001998-25, D-CAN-545, U1111-1113-9336
Study First Received: October 16, 2008
Last Updated: August 6, 2012
Health Authority: European Union: European Medicines Agency

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

Additional relevant MeSH terms:
Hypertension
Obesity
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Candesartan
Candesartan cilexetil
Antihypertensive Agents
Hydrochlorothiazide
Calcium Channel Blockers
Insulin
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 26, 2014