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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Hydrochlorothiazide; Drug: Candesartan cilexetil

Study type: Interventional

Funder types: Industry

Identifiers

NCT00383929

D2456C00001

Eudract No. 2005-005718-19

Details and patient eligibility

About

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.

Enrollment: 1,979 patients

Sex: All

Ages: 20 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,979 participants in 3 patient groups

1

Experimental group

Description:

Candesartan Cilexetil (CC) /HCT 32/12.5mg

Treatment:

Drug: Hydrochlorothiazide

Drug: Candesartan cilexetil

Drug: Hydrochlorothiazide

2

Experimental group

Description:

Candesartan Cilexetil (CC) /HCT 32/25mg

Treatment:

Drug: Hydrochlorothiazide

Drug: Candesartan cilexetil

Drug: Hydrochlorothiazide

3

Experimental group

Description:

Candesartan Cilexetil monotherapy

Treatment:

Drug: Candesartan cilexetil