A 52 Week Study to Evaluate the Effects of Losartan With or Without HCTZ on Plasma Glucose, Metabolic Parameters, Blood Pressure in Hypertensive Patients With Metabolic Syndrome (0954A-331)

52 Week Study to Evaluate the Effects of LOSARTAN 50 mg, 100 mg, 100/12.5 mg HCTZ, 100/25 mg HCTZ on Metabolic Parameters, Blood Pressure and Safety in Hypertensive Patients With Metabolic Syndrome

To determine if a one year treatment Losartan with or without HCTZ at different dosages have an effect on metabolic parameters in patients with hypertension and the metabolic syndrome.

Study Overview

• Status: Completed
• Conditions: Hypertension; Metabolic Disorder
• Intervention / Treatment: Drug: losartan potassium (+) hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 1738
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• An Adult Patient (At Least 18 Years Of Age) With A Clinical Identification Of The Metabolic Syndrome Using The IDF Definition:

  • abdominal (central) obesity as defined by the waist circumference in men of > 102 cm and women of > 88 cm or a BMI equal or greater than 30 kg/m2

and untreated hypertension with bp equal or greater than 140/90 mm Hg but bp < 180/110 mm Hg

or a patient receiving one or two antihypertensive agent(s) (diuretics, ace inhibitors, angiotensin ii receptor blockers, calcium channel blockers and beta-blockers will need to be discontinued) and whose blood pressure is not controlled:

• bp equal or greater than 140/90 mm Hg but equal or less than 160/100 mm Hg

or a patient whose hypertension is controlled (< 140/90 mm hg) with a single anti-hypertensive agent (diuretics, ace inhibitors, and angiotensin II receptor blockers, calcium channel blockers and beta-blockers will need to be discontinued) but who is unsatisfied or experiencing side effects warranting a discontinuation of the previous treatment and at one of the following:

• Fasting plasma glucose equal or greater than 5.6 mmol/L and < 7.0 mmol/L
• Triglycerides > 1.7 mmol/L or specific treatment for this lipid abnormality
• HDL-c in men < 0.9 mmol/L and in women < 1.1 mmol/L or specific treatment for this lipid abnormality

Exclusion Criteria:

• A Patient With A Diagnosis Of Type II Diabetes Defined As Fasting Blood Glucose Level Equal Or Greater Than 7.0 Mmol/L Or A 2hpg In A 75-G OGTT Equal Or Greater Than 11.1 Mol/L Or Using Any Anti-Hyperglycemic Agents
• Known Secondary Hypertension Of Any Aetiology (E.G., Uncorrected Renal Artery Stenosis, Malignant Hypertension, Or Hypertensive Encephalopathy)
• Patient Intolerant To Any Component Of Losartan 50 Mg / Losartan 100 Mg / Losartan 100 Mg + Hctz 12.5 Mg / Losartan 100 Mg + Hctz 25 Mg Or With A Documented History Of Angioedema
• Patient With Confirmed Clinically Significant Renal Or Hepatic Dysfunction And/Or Electrolyte Imbalance On The Basis Of The Case History Or A Recent Laboratory Test (Serum Creatinine > 130 Mmol/L Or Creatinine Clearance < 45 Ml/Min, Ast > 2 Times Above The Normal Range, Alt > 2 Times Above The Normal Range, Serum Potassium < 3.5 Or > 5.5 Meq/L)
• Patient With Symptomatic Heart Failure (Classes 3 And 4)
• Patient With A Prior Myocardial Infarction Or Stroke Within The Last 6 Months
• Patient Who Has Undergone Percutaneous Coronary Angioplasty Or Coronary Artery Bypass Within The Last 3 Months
• Pregnant Woman Or A Woman Of Childbearing Potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Losartan (MK0954) / Losartan + HCTZ (MK0954A)	Drug: losartan potassium (+) hydrochlorothiazide; All patients received Losartan 50mg at Visit 2 titrated to Losartan 100mg (if target BP not achieved) titrated to Losartan 100mg + HCTZ 12.5mg (if necessary) up to Losartan 100mg + HCTZ 25mg. Duration of treatment was one year.; Other Names: Cozaar/Hyzaar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin A1c Between 52 Weeks and Baseline	Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.	52 Weeks - Baseline
Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments	Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.	52 Weeks - Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Blood Pressure	Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks	52 Weeks
Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments	Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.	52 Weeks - Baseline
Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments	Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.	52 Weeks - Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Waist Circumference Between Baseline and 52 Week Assessments	Absolute change in Waist Circumference between baseline and 52 week assessments	52 Weeks - Baseline
Change in Body Mass Index Between Baseline and 52 Week Assessments	Absolute change in Body Mass Index Baseline and 52 week assessments	52 Weeks - Baseline
Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments	Percent Change in LDL-C Between Baseline and 52 week assessments: 100% x [(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)].	52 Weeks - Baseline
Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments	Percent Change in HDL-C Between Baseline and 52 week assessments: 100% x [(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)].	52 Weeks - Baseline
Percent Change in Triglycerides Between Baseline and 52 Week Assessments	Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x [(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)].	52 Weeks - Baseline
Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments	Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x [(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)].	52 Weeks - Baseline
Absolute Change in Uric Acid Between Baseline and 52 Week Assessments	Absolute Change in Uric Acid Between Baseline and 52 week assessments: Uric Acid 52 weeks - Uric Acid Baseline.	52 Weeks - Baseline
Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments	Absolute Change in C Reactive Protein Between Baseline and 52 week assessments: C Reactive Protein 52 weeks - C Reactive Protein Baseline.	52 Weeks - Baseline

Collaborators and Investigators

• Sponsor: Organon and Co
• Investigators: Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Racine N, Hamet P, Sampalis JS, Longo N, Bastien N. A 52-week prospective, cohort study of the effects of losartan with or without hydrochlorothiazide (HCTZ) in hypertensive patients with metabolic syndrome. J Hum Hypertens. 2010 Nov;24(11):739-48. doi: 10.1038/jhh.2010.3. Epub 2010 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2005
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: October 17, 2007
• First Submitted That Met QC Criteria: October 17, 2007
• First Posted (Estimated): October 18, 2007

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Metabolic Diseases; 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
• Other Study ID Numbers: 0954A-331; MK0954A-331; 2007_030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php