Antihypertensive Efficacy and Safety of Candesartan/HCT 32/12.5 and 32/25 mg in Comparison With Candesartan 32 mg

Study Overview
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Brief Summary
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In this study it is intended to compare the blood pressure lowering effect of the combination of candesartan cilexetil (candesartan) 32 mg and hydrochlorothiazide (HCT) 25 mg and the combination of candesartan 32 mg and HCT 12.5 mg to that of candesartan 32 mg alone in patients whose blood pressure is not well controlled on candesartan 32 mg monotherapy. The Primary Objectives are to compare sitting BP lowering effect of candesartan/HCT 32/25 mg and candesartan/HCT 32/12.5 mg with that of candesartan 32 mg, respectively.

Official Title
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A Double Blind, Randomised, 3-Arm Parallel Group, Multicentre, 8-Week, Phase III Study to Assess Antihypertensive Efficacy and Safety of the Combination of Candesartan Cilexetil (CC) /HCT 32/12.5mg and 32/25mg vs. CC 32mg Alone in Patients With Inadequate BP Control on Monotherapy With CC 32mg

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Candesartan cilexetil
* Drug: Hydrochlorothiazide
* Drug: Hydrochlorothiazide


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, which the patient and the physician are willing to withdraw at enrolment and change to candesartan monotherapy Mean sitting DBP 90-114 mmHg Patients will be eligible for randomisation (Visit 4) if they fulfil the following criterion: Mean sitting DBP 90-114 mmHg on treatment with candesartan 32 mg monotherapy (after 2 weeks with candesartan 16 mg and 6 weeks with candesartan 32 mg monotherapy). The run-in period should not be shorter than 8 weeks. Exclusion Criteria: Involvement in the planning and conduct of the study (applies to both AstraZeneca staff, CRO staff or staff at the investigational centre) Pregnant or lactating women, or women of childbearing potential not practising an adequate method of contraception eg, intrauterine device, oral contraception or progesterone implant and verified by a negative pregnancy test at Visit 1 Secondary or malignant hypertension Sitting SBP of 180 mmHg or more Patients who are treated with candesartan 16 mg in combination with a diuretic or with candesartan 32 mg with or without any additional antihypertensive treatment 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 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 Chronic liver disease or known liver enzyme values above three times the upper limit of the reference range for S-ASAT or S-ALAT Concomitant or previous treatment with other investigational drugs within 20 days of enrolment Previous enrolment in the present study S-creatinine of 180 μmol/l or above for men and of 140 μmol/l or above for women S-sodium or S-potassium outside the reference range Less than 85% compliance with study medication during the run-in phase

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 |
| --- | --- |
| Experimental: 1<br>Candesartan Cilexetil (CC) /HCT 32/12.5mg | Drug: Candesartan cilexetil<br>* 32mg oral<br>* Other names: ATACAND;Drug: Hydrochlorothiazide<br>* 12.5 mg oral<br>* Other names: HCTZ;|
| Experimental: 2<br>Candesartan Cilexetil (CC) /HCT 32/25mg | Drug: Candesartan cilexetil<br>* 32mg oral<br>* Other names: ATACAND;Drug: Hydrochlorothiazide<br>* 25 mg oral<br>* Other names: HCTZ;|
| Experimental: 3<br>Candesartan Cilexetil monotherapy | Drug: Candesartan cilexetil<br>* 32mg oral<br>* Other names: ATACAND;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (reduction) in sitting BP (24 hours after dose) |  | Assessed from baseline (randomisation) to the end of the study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with controlled sitting BP in each treatment group |  | Assessed at the end of the study | 
| Occurrence of Adverse Events and discontinuation of study medication due to AEs from baseline (randomisation) to the end of the study |  | Assessed from baseline (randomisation) to the end of the study. | 

 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