Telmisartan With or Without Hydrochlorothiazide (HCTZ) Compared With Losartan With or Without HCTZ in Mild to Moderate Hypertensive Patients

Study Overview
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Brief Summary
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Study to assess the efficacy of telmisartan 40-80 mg once daily compared with losartan 50-100 mg once daily in hypertensive patients evaluated by change from baseline in diastolic blood pressure (DBP) during the last 6 hours of the 24-hour dosing interval, at the end of the 12 weeks period of monotherapy treatment (ABPM - ambulatory blood pressure measurement). Secondary objectives: Changes from baseline in BP at the end of the monotherapy period of treatment and at the end of the study, evaluated by sphygmomanometric blood pressure measurement and ABPM Safety: Incidence of adverse events (AE's); withdrawal due to adverse events; laboratory parameters

Official Title
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A PROBE (Prospective, Randomised, Open-label, Blinded Endpoint) Trial to Investigate the Efficacy and Safety of Telmisartan 40-80 mg Once Daily Compared With Losartan 50-100 mg Once Daily Over a Period of 12 Weeks, and of Telmisartan 80 mg + HCTZ 12.5 mg Once Daily Compared With Losartan 100 mg Once Daily + HCTZ 12.5 mg Once Daily Over a Period of Further 12 Weeks in Mild to Moderate Hypertensive Patients (Grade 1 and Grade 2 WHO-ISH Guidelines 1999)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Losartan
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Mild-to-moderate essential hypertension defined as a mean diastolic blood pressure (DBP) ≥ 95 mmHg and < 110 mmHg and systolic blood pressure (SBP) < 180 mmHg measured by manual cuff sphygmomanometer at the end of the wash-out period Written informed consent Exclusion Criteria: Nursing, pregnancy or childbearing potential women, post-menopausal women will be enrolled with last menstruation > 1 year prior to start wash-out phase or surgically sterile Secondary hypertension Malignant hypertension (retinal haemorrhage, exudates or papillary oedema) Clinically significant sodium depletion as defined by serum sodium level < 130 mEq/L and/or clinically significant hyperkaliemia as defined by serum potassium level > 5.5 mEq/L or clinically significant hypokaliemia as defined by serum potassium level < 3.0 mEq/L Atrial fibrillation or frequent ventricular ectopic beats or other arrhythmias which, in the investigator opinion could compromise patient's participation to the trial Congestive heart failure (CHF) (NYHA (New York Heart Association) functional class CHF III-IV) Angina pectoris or myocardial infarction Cardiac surgery within the past 3 months prior to start the wash-out period Stroke within the past 6 months prior to start the wash-out period Renal insufficiency defined as creatininaemia > 2mg/dl Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post renal transplant, presence of only one functioning kidney Liver insufficiency, defined as bilirubinaemia > 2mg/dl and AST (aspartate aminotransferase) or ALT (alanine-aminotransferase) > twice the upper normal range Clinically significant metabolic and endocrine disease Autoimmune disease Previous history of angioedema Body mass index > 30kg/m2 Arm circumference > 32 cm Any condition that may be likely to compromise patients participation to the trial (alcohol or drug abuse, disability illness, etc.) Concomitant therapy with antihypertensive drugs non permitted by protocol, corticosteroids or drugs known to affect blood pressure Concomitant use of lithium or cholestyramine or colestipol resins (potential drug interactions with HCTZ) Investigational drug treatment within the past 30 days before the enrolment or concurrent participation to any other trial Sensitivity, significant adverse reaction or contraindications to the study drugs (telmisartan, losartan, HCTZ) Predictable lack of patient co-operation

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan<br> | Drug: Telmisartan<br> <br> |
| Experimental: Telmisartan + Hydrochlorothiazide<br> | Drug: Telmisartan<br> <br> Drug: Hydrochlorothiazide<br> <br> |
| Active Comparator: Losartan<br> | Drug: Losartan<br> <br> |
| Active Comparator: Losartan + Hydrochlorothiazide<br> | Drug: Losartan<br> <br> Drug: Hydrochlorothiazide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in diastolic blood pressure (DBP) during the last 6 hours (ABPM - ambulatory blood pressure measurement) of the 24-hour dosing interval at the end of the monotherapy period of treatment |  | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in DBP during the last 6 hours (ABPM) of the 24-hour dosing interval at the end of the study |  | Baseline and week 24 | 
| Change from baseline in systolic blood pressure (SBP) during the last 6 hours (ABPM) of the 24-hour dosing interval |  | Baseline, week 12 and 24 | 
| Change from baseline in DBP/SBP during the last 2 hours (ABPM) of the 24-hour dosing interval (trough BP) |  | Baseline, week 12 and 24 | 
| Changes from baseline in trough cuff (sphygmomanometer) SBP/DBP |  | Baseline, week 12 and 24 | 
| Changes from baseline in SBP/DBP of 24 hours mean ABPM |  | Baseline, week 12 and 24 | 
| Comparison of SBP/DBP ABPM tracing profile |  | Week 12 and 24 | 
| Smoothness index in comparison with baseline |  | Baseline, week 12 and 24 | 
| Number of responders |  | Week 12 and 24 | 
| Number of controlled responders |  | Week 12 and 24 | 
| Number of patients who withdraw due to lack of efficacy |  | 24 weeks | 
| Number of patients with adverse events |  | 24 weeks | 
| Number of patients who withdraw due to adverse events |  | 24 weeks |