Antihypertensive Efficacy and Safety of Candesartan/HCT 32/25 mg in Comparison With Individual Components and Placebo

Study Overview
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Brief Summary
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The aim is to compare the blood pressure lowering effect of the combination of candesartan cilexetil (candesartan) 32 mg and hydrochlorothiazide (HCT) 25 mg to that of candesartan 32 mg alone, HCT 25 mg alone and placebo in hypertensive adults.

Official Title
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A Double-blind, Randomised, 4-arm Parallel Group, Multicentre, 8-week, Phase III Study to Assess the Antihypertensive Efficacy and Safety of the Combination of Candesartan Cilexetil (CC) 32 mg and Hydrochlorothiazide (HCT) 25 mg Compared With CC 32 mg, HCT 25 mg and Placebo in Hypertensive Adults

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Candesartan cilexetil
* Drug: Hydrochlorothiazide
* Drug: Candesartan/HCT 32/25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be eligible for enrolment into the study (Visit 1) if they fulfil all of the following criteria: Provision of signed Informed Consent Primary hypertension, untreated or treated with a maximum of 2 antihypertensive drugs (substances), which the patient and the physician are willing to withdraw at enrolment and replace with placebo. Mean sitting DBP 90-114 mmHg (value calculated in the eCRF) at Visits 1 and 2 Patients will be eligible for randomisation (Visit 4) if they fulfil the following criterion: Mean sitting DBP of 90-114 mmHg (value calculated in the eCRF) at the end of the 4-week single-blind placebo run-in period. The run-in period should not be shorter than 4 weeks. Exclusion Criteria: Pregnant or lactating women, or women of childbearing potential not practising an adequate method of contraception eg, intrauterine device, oral contraception or progesterone implant. Pregnancy must be excluded by a negative pregnancy test at Visit 1. Secondary or malignant hypertension Sitting SBP of 180 mmHg or more Myocardial infarction, stroke, coronary bypass surgery or transient ischaemic attack within 6 months before enrolment Angina pectoris requiring more treatment than short-acting nitrates Chronic use of NSAIDs Aortic or mitral valve stenosis Cardiac failure requiring treatment Cardiac arrhythmia requiring treatment Gout Renal artery stenosis or kidney transplantation Intravascular volume depletion Hypersensitivity to any component of the investigational products or to any sulphonamide derived drugs Concomitant disease which may interfere with the assessment of the patient Past or present alcohol or drug abuse, or any condition associated with poor compliance that in the opinion of the investigator might affect the patient's participation in the study Chronic liver disease Concomitant or previous treatment with any other investigational drug within 20 days of enrolment Previous enrolment in the present study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 4<br>Placebo | |
| Active Comparator: 2<br>Candesartan cilexetil | Drug: Candesartan cilexetil<br>* 32 mg oral tablet<br>* Other names: ATACAND;|
| Active Comparator: 3<br>Hydrochlorothiazide (HCT) | Drug: Hydrochlorothiazide<br>* 25 mg oral tablet<br>* Other names: HCTZ;|
| Experimental: 1<br>Candesartan cilexetil + Hydrochlorothiazide Combination | Drug: Candesartan cilexetil<br>* 32 mg oral tablet<br>* Other names: ATACAND;Drug: Hydrochlorothiazide<br>* 25 mg oral tablet<br>* Other names: HCTZ;Drug: Candesartan/HCT 32/25 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sitting Diastolic Blood Pressure (DBP) From Baseline to the End of the Study (From Baseline to 8 Weeks). | Change (reduction) in sitting DBP at the end of the study, when compared to sitting DBP at baseline. | 8 weeks | 
| Change in Sitting Systolic Blood Pressure (SBP) From Baseline to the End of the Study (Baseline to 8 Weeks) | Change (reduction) in sitting SBP at the end of the study, when compared to sitting SBP at baseline. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With Controlled Sitting DBP and Sitting SBP in Each Treatment Group at the End of the Study | Controlled sitting SBP and sitting DBP are defined as having sitting SBP < 140 mmHg and sitting DBP < 90 mmHg at the end of the study | 8 weeks | 
| Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Hypertension Control Rate at the End of the Study (Patients With Controlled Sitting SBP and Sitting DBP). |  | Baseline to 8 weeks | 
| To Describe Safety and Tolerability of the Study Treatments With Regard to Adverse Events Including Those That Lead to Treatment Discontinuation as Well as With Regard to Pulse Rate, Laboratory, Electrocardiographic and Physical Examination Findings. |  | Baseline to 8 weeks | 
| To Compare Treatment With Candesartan/HCT 32/25 mg to Each of Its Components With Regard to Change From Baseline to Week 8 in Standing DBP and Standing SBP. |  | Baseline to 8 weeks | 
| To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Control Rate at the End of the Study (Patients With Controlled Sitting DBP Are Defined as Having a Sitting DBP <90 mmHg at the End of the Study). |  | Baseline to 8 weeks | 
| To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Responder Rate (Decrease in Sitting DBP ≥10 mmHg From Baseline to the End of the Study or a Sitting DBP <90 mmHg at the End of the Study). |  | Baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure reduction, combination therapy, candesartan cilexetil, hydrochlorothiazide