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

A Prospective, Randomized, Double-Blind, Double-Dummy, Titration-to-Response Trial Comparing MICARDIS® (Telmisartan) (40 & 80 mg QD) and COZAAR® (Losartan) (50 & 100 mg QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring

The primary aim of the trial is to compare the influence of MICARDIS® (telmisartan 40-80 mg) and COZAAR® (losartan 50-100 mg) in lowering ambulatory diastolic blood pressure (DBP) during the last 6 hours of the 24-hour dosing interval as measured by ABPM after 8-weeks treatment. 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®, once daily; Drug: High dose of COZAAR®, once daily

• Study Type: Interventional
• Enrollment (Actual): 333
• 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, on the last visit (Visit 6) of the four-week placebo run-in period (baseline BP). The manual cuff value is calculated as the mean of three seated measurements taken two minutes apart, after the patient has been seated quietly for 5 minutes
• A 24-mean DBP of ≥ 85 mmHg at Visit 7 as measured by ABPM
• Age 18 years or older
• Ability to stop current antihypertensive therapy without risk to the patient (investigator's discretion)
• Ability to provide written informed consent

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 practicing acceptable means of birth control, do NOT plan to continue using this method throughout the study and do NOT agree to submit to periodic pregnancy testing during participation in studies of ≥ 3-months duration. Acceptable methods of birth control include intrauterine device (IUD), oral, implantable or injectable contraceptives
• 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) greater than two times the upper limit of normal
  • Serum creatinine > 2.3 mg/dL
• Clinically relevant sodium depletion, hyperkalemia, or hypokalemia
• Uncorrected volume depletion
• Primary aldosteronism
• Biliary obstructive disorders
• Known or suspected secondary hypertension
• Hereditary fructose intolerance
• Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney; post-renal transplant patients, presence of only one functioning kidney
• Congestive heart failure (NYHA functional class congestive heart failure (CHF) class III-IV)
• Unstable angina within the past three months
• Stroke within the past six months
• Myocardial infarction or cardiac surgery within the past three months
• Percutaneous transluminal coronary angioplasty (PTCA) within the past three months
• History of angioedema
• 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%
• Known drug or alcohol dependency within the past 6 months
• Concomitant administration of medications known to affect blood pressure, except medications allowed by the protocol
• Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 ante meridien (AM)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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®	Drug: Placebo; Drug: Low dose of COZAAR®, once daily; Other Names: Losartan
Active Comparator: High dose of COZAAR®	Drug: Placebo; Drug: High dose of COZAAR®, 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: March 1, 2000
• Primary Completion (Actual): December 1, 2000

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: 502.343