Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension.
This study has been completed.
Sponsor:
Takeda Pharma GmbH
Information provided by (Responsible Party):
Takeda Global Research & Development Center, Inc. ( Takeda Pharma GmbH )
ClinicalTrials.gov Identifier:
NCT00775814
First received: October 16, 2008
Last updated: August 6, 2012
Last verified: August 2012
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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 Global Research & Development Center, Inc.:
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
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 Pharma GmbH
Investigators
| Study Director: | Medical Director | Takeda Pharma GmbH |
More Information
No publications provided
| Responsible Party: | Takeda Global Research & Development Center, Inc. ( Takeda Pharma GmbH ) |
| 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 Global Research & Development Center, Inc.:
|
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 May 23, 2013