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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00546052
First received: October 17, 2007
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hypertension
Metabolic Disorder
Drug: losartan potassium (+) hydrochlorothiazide
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change in Hemoglobin A1c Between 52 Weeks and Baseline [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.

  • Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.


Secondary Outcome Measures:
  • Target Blood Pressure [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks

  • Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.

  • Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.


Other Outcome Measures:
  • Change in Waist Circumference Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute change in Waist Circumference between baseline and 52 week assessments

  • Change in Body Mass Index Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute change in Body Mass Index Baseline and 52 week assessments

  • Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Percent Change in LDL-C Between Baseline and 52 week assessments: 100% x [(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)].

  • Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Percent Change in HDL-C Between Baseline and 52 week assessments: 100% x [(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)].

  • Percent Change in Triglycerides Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x [(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)].

  • Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x [(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)].

  • Absolute Change in Uric Acid Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute Change in Uric Acid Between Baseline and 52 week assessments: Uric Acid 52 weeks - Uric Acid Baseline.

  • Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments [ Time Frame: 52 Weeks - Baseline ] [ Designated as safety issue: No ]
    Absolute Change in C Reactive Protein Between Baseline and 52 week assessments: C Reactive Protein 52 weeks - C Reactive Protein Baseline.


Enrollment: 1738
Study Start Date: September 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cozaar/Hyzaar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00546052

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Additional Information:
Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00546052     History of Changes
Other Study ID Numbers: 0954A-331, MK0954A-331, 2007_030
Study First Received: October 17, 2007
Results First Received: January 8, 2009
Last Updated: July 16, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Hypertension
Metabolic Diseases
Metabolic Syndrome X
Vascular Diseases
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Hydrochlorothiazide
Losartan
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 28, 2014