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

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)

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

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Telmisartan; Drug: Losartan; Drug: Hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan	Drug: Telmisartan
Active Comparator: Losartan	Drug: Losartan
Experimental: Telmisartan + Hydrochlorothiazide	Drug: Telmisartan; Drug: Hydrochlorothiazide
Active Comparator: Losartan + Hydrochlorothiazide	Drug: Losartan; Drug: Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Number of patients with adverse events	24 weeks
Number of patients who withdraw due to adverse events	24 weeks
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): January 1, 2002

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Losartan; Hydrochlorothiazide; Telmisartan
• Other Study ID Numbers: 502.316