A Trial Comparing MICARDIS® (Telmisartan) and COZAAR® / LORZAAR® (Losartan) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring (ABPM) (TOPAS)

A Prospective, Randomised, Double-Blind, Double-Dummy, Titration-to-Response Trial Comparing MICARDIS® (Telmisartan) (40 or 80 mg p.o. Once Daily) and COZAAR® / LORZAAR® (Losartan) (50 or 100 mg p.o. Once Daily) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring (TOPAS STUDY = Telmisartan and LOsartan ComParative ABPM Study)

The primary aim of the trial is to compare the influence of MICARDIS® (telmisartan) and COZAAR® / LORZAAR® (losartan) in lowering ambulatory diastolic blood pressure (DBP) during the last 6 hours of the 24-hour dosing interval as measured by ABPM. Secondary objectives include evaluations of: 1) change from baseline in mean systolic blood pressure (SBP) during the last 6 hours of the 24-hour dosing interval as measured by ABPM, 2) changes from baseline in SBP and DBP during other periods during the 24-hour ABPM profile, 3) changes from baseline in mean seated trough SBP and DBP as measured by manual cuff sphygmomanometer, and 4) responder rates based on both ABPM and trough cuff blood pressure

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Low dose of MICARDIS®, once daily; Drug: High dose of MICARDIS®, once daily; Drug: Low dose of COZAAR® / LORZAAR®, once daily; Drug: High dose of COZAAR® / LORZAAR®, once daily

• Study Type: Interventional
• Enrollment (Actual): 387
• 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:

• Mild-to-moderate hypertension defined as a mean seated diastolic blood pressure of ≥ 95 mmHg and ≤ 109 mmHg, measured by manual cuff sphygmomanometer, at Visit 3 (baseline cuff BP)
• A 24-mean DBP of ≥ 85 mmHg at Visit 4 as measured by ABPM
• Age 18 years or older
• Ability to stop current antihypertensive therapy without risk to the patient (investigator's discretion)
• Patient's written informed consent in accordance with good clinical practice (GCP) and local legislation

Exclusion Criteria:

• Pre-menopausal women (last menstruation ≤ 1 year prior to start of run-in period) who:

  • are not surgically sterile; and/or
  • are nursing
  • are of child-bearing potential and are NOT practising acceptable means of birth control, do NOT plan to continue using this method throughout the study. Acceptable methods of birth control include oral, implantable or injectable contraceptives
• Known or suspected secondary hypertension
• Mean sitting SBP ≥ 180 mmHg or mean sitting DBP ≥ 110 mmHg during any visit of the placebo run-in period

• Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

  • Serum glutamate-pyruvate-transaminase (alanine aminotransferase) or serum glutamate-oxaloacetate-transaminase (aspartate aminotransferase) > than 2 times the upper limit of normal range
  • Serum creatinine > 2.3 mg/dL (or > 203 µmol/l)
• Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney; patients post-renal transplant or with only one kidney
• Clinically relevant sodium depletion, hypokalaemia, or hyperkalaemia
• Uncorrected volume depletion
• Primary aldosteronism
• Hereditary fructose intolerance
• Biliary obstructive disorders
• Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists
• History of drug or alcohol dependency within 6 months
• Chronic administration of any medications known to affect blood pressure, except medications allowed by the protocol
• Any investigational therapy within one month of signing the informed consent form
• Congestive heart failure (NYHA functional class congestive heart failure (CHF) class III-IV)
• Unstable angina within the past six months
• Stroke within the past six months
• Myocardial infarction or cardiac surgery within the past six months
• Percutaneous transluminal coronary angioplasty (PTCA) within the past six months
• Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator
• Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
• Patients with insulin-dependent diabetes mellitus whose diabetes hast not been stable and controlled for at least the past three months as defined by an HbA1c ≥ 10%
• Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 ante meridiem (AM)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low dose of MICARDIS®	Drug: Placebo; Drug: Low dose of MICARDIS®, once daily; Other Names: Telmisartan
EXPERIMENTAL: High dose of MICARDIS®	Drug: Placebo; Drug: High dose of MICARDIS®, once daily; Other Names: Telmisartan
ACTIVE_COMPARATOR: Low dose of COZAAR® / LORZAAR®	Drug: Placebo; Drug: Low dose of COZAAR® / LORZAAR®, once daily; Other Names: Losartan
ACTIVE_COMPARATOR: High dose of COZAAR® / LORZAAR®	Drug: Placebo; Drug: High dose of COZAAR® / LORZAAR®, once daily; Other Names: Losartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean diastolic blood pressure	Measured during the last 6 hours of the 24-hour dosing interval using ABPM	Up to 8 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean systolic blood pressure	Measured during the last 6 hours of the 24-hour dosing interval using ABPM	Up to 8 weeks after start of treatment
Changes from baseline in diastolic and systolic blood pressure	Measured during other times of the 24-hour ABPM profile (e.g. 24-hour mean, morning mean, daytime mean and nighttime mean)	Up to 8 weeks after start of treatment
Changes from baseline in mean seated trough diastolic blood pressure and systolic blood pressure	Triplicate measurement in two minute intervals after 5 minutes of rest, in seated position using sphygmomanometer	Up to 8 weeks after start of treatment
Assessment of responder rates on ABPM		Baseline, 8 weeks after start of treatment
Assessment of responder rates on trough cuff blood pressure		Baseline up to 8 weeks after start of treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (ACTUAL): February 1, 2001

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (ESTIMATE): July 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan; Telmisartan
• Other Study ID Numbers: 502.344