Telmisartan Compared to Losartan + Hydrochlorothiazide in Patients With Mild-to-moderate Essential Hypertension

A Prospective Randomised Open-Label Blinded Endpoint Trial Comparing Telmisartan 80 mg and Losartan 50 mg + Hydrochlorothiazide 12.5 mg (Fixed Dose Combination) in Patients With Mild-to-Moderate Essential Hypertension Using Ambulatory Blood Pressure Monitoring

The general aim and clinical objective of this trial is to determine the effect of telmisartan 80 mg compared to losartan 50 mg + HCTZ (Hydrochlorothiazide) 12.5 mg on reduction of blood pressure (BP) in patients with mild to moderate hypertension as assessed by 24 hour Ambulatory Blood Pressure Monitoring (ABPM) and trough sitting BP cuff measurements at the end of the treatment.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 715
• Phase: Phase 3

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:

• Mild-to-moderate essential hypertension defined as a mean seated diastolic blood pressure measurement of ≥ 95 mmHg measured by manual cuff sphygmomanometer, on Visit 2 of the four-week placebo run-in period (baseline)
• Mean seated systolic blood pressure ≥ 140 mmHg, measured by manual cuff at baseline (Visit 2)
• A 24-hour mean diastolic blood pressure , measured by ABPM, of ≥ 85 mmHg evaluated at baseline (Visit 3)
• Age 18 or older
• Patient's written informed consent in accordance with GCP (Good Clinical Practice) and local legislation

Exclusion Criteria:

• Pre-menopausal women (last menstruation ≤ 1 year prior to date of consent):

  • Who are not surgically sterile (hysterectomy, tubal ligation)
  • Who are NOT practising acceptable means of birth control or who do NOT plan to continue using an acceptable method throughout the trial. Acceptable methods of birth control include IUD (intrauterine device), oral, implantable or injectable contraceptives
  • Who have a positive urine pregnancy test
  • Who are nursing
• Mean seated diastolic blood pressure (DBP) > 114 mmHg or mean seated systolic BP > 200 mmHg, by manual cuff

• Any known hepatic and/or renal dysfunction as defined by the following laboratory parameters:

  • SGPT (serum glutamate pyruvate transaminase) (ALT) or SGOT (serum glutamate oxaloacetate transaminase) (AST) greater than two times the upper limit of normal
  • Serum creatinine > 1.8 mg/dl (or 159 µmol/l)
• Clinically relevant hypokalemia
• Known or suspected secondary hypertension
• Known bilateral renal artery stenosis; renal artery stenosis in a solitary kidney; post-renal transplant patients, presence of only one functioning kidney.
• Congestive heart failure (CHF) (NYHA (New York Heart Association) class CHF III-IV)
• Unstable angina within the past 3 months; stable angina where a change in nitrate therapy (dose or frequency) during the run-in period was required
• Stroke within the past 6 months prior to start of run-in period
• Myocardial infarction or cardiac surgery within the past 3 months prior to start of run-in period
• PTCA (percutaneous transluminal coronary angioplasty) within the past 3 months prior to start of run-in period
• Previous history of angioedema
• Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator
• Hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve
• Patients with unstable insulin-dependent diabetes mellitus (risk of hypoglycemia or HbA1c ≥ 10 % in history within 6 months prior to start of run-in period)
• Known drug or alcohol dependency within the past 6 months period prior to start of run-in period
• Concomitant administration of medications known to affect blood pressure, except medications allowed by the protocol
• Patients receiving any investigational therapy within one month of signing the informed consent form
• Known hypersensitivity to any component of the formulations
• Any clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of trial medication
• Concomitant use of lithium or cholestyramine or colestipol resins (potential drug interactions with HCTZ)

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telmisartan; 4 weeks placebo run-in, 6-weeks fixed dose period	Drug: Placebo; Drug: Telmisartan
Active Comparator: Losartan + Hydrochlorothiazide; 4 weeks placebo run-in, 6-weeks fixed dose period (Losartan 50 mg / HCTZ 12.5 mg)	Drug: Placebo; Drug: Losartan + Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in 24-hour mean diastolic blood pressure measured by ABPM	Baseline (Day 28 of run-in period) and day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in 24-hour mean systolic blood pressure measured by ABPM	Baseline (Day 28 of run-in period) and day 42
Change from baseline in systolic and diastolic blood pressures during other time periods during the 24-hour ABPM profile	Baseline (Day 28 of run-in period) and day 42
Change from baseline (Visit 2) in trough systolic and diastolic blood pressures measured by cuff sphygmomanometer	Baseline (Day 28 of run-in period) and day 42
Number of patient with of adverse events	up to 10 weeks
Changes from baseline in pulse rate	Baseline (Day 28 of run-in period) and day 42
Changes in physical examination	Screening and day 43
Changes in laboratory parameters	Screening and day 43
Changes in 12-lead electrocardiogram (ECG)	Baseline (Day 29 of run-in period) and day 43

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): December 1, 1998

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 7, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential 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: 502.257