Clinical trial NCT00775814: Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Hypertension
Keywords: Hypertension
Drug Therapy
Blood Pressure
Insulin, Resistant
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-10-20
Enrollment: 188
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The change from Baseline in Blood pressure (mean reduction in Diastolic Blood Pressure measured at trough).
timeFrame: End of Treatment
Secondary outcomes:
measure: The change from Baseline in Adiponectin.
timeFrame: At Final Visit.
measure: The change from Baseline in high sensitivity C-Reactive Protein.
timeFrame: At Final Visit.
measure: The change from Baseline in Fasting Plasma Glucose.
timeFrame: At Final Visit.
measure: The change from Baseline in Fasting Plasma Insulin.
timeFrame: At Final Visit.
measure: The change from Baseline in Insulin Resistance (assessed by Homeostasis Model Assessment Insulin Resistance).
timeFrame: At Final Visit.
measure: The change from Baseline in Lipid Parameters (total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides).
timeFrame: At Final Visit.
measure: The change from Baseline in Fibrinogen.
timeFrame: At Final Visit.
measure: The change from Baseline in Prospective Cardiovascular Münster risk score for the assessment of coronary heart disease.
timeFrame: At Final Visit.
measure: The change from Baseline in 24-hour mean blood pressure as assessed by Ambulatory Blood Pressure Measurement.
timeFrame: At Final Visit.
measure: The change from Baseline in Daytime and night-time mean blood pressure Ambulatory Blood Pressure Measurement.
timeFrame: At Final Visit.
measure: The change from Baseline in Systolic Blood Pressure.
timeFrame: End of Treatment.
Other outcomes:
Locations:
city: Bad Dürrheim
country: Germany
state: Baden-Württemberg
city: Balingen
country: Germany
state: Baden-Württemberg
city: Deggingen
country: Germany
state: Baden-Württemberg
city: Rottweil
country: Germany
state: Baden-Württemberg
city: Spaichingen
country: Germany
state: Baden-Württemberg
city: Ingolstadt
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Passau
country: Germany
state: Bayern
city: Schauenburg
country: Germany
state: Hessen
city: Bocholt
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Isselburg
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Roetgen
country: Germany
state: Nordrhein-Westfalen
city: Troisdorf
country: Germany
state: Nordrhein-Westfalen
city: Wesseling
country: Germany
state: Nordrhein-Westfalen
city: Roedersheim-Gronau
country: Germany
state: Rheinland-Pfalz
city: Dresden
country: Germany
state: Sachsen
city: Freital
country: Germany
state: Sachsen
city: Machem
country: Germany
state: Sachsen
city: Markkleeberg
country: Germany
state: Sachsen
city: Wermsdorf
country: Germany
state: Sachsen
city: Bad Segeberg
country: Germany
state: Schleswig-Holstein
city: Berlin
country: Germany
Study officials:
affiliation: Takeda Pharma Gmbh, Aachen (Germany)
name: Medical Director
role: STUDY_DIRECTOR
References: