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)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00546052
• Collaborator: (none)
• Enrollment: 1,738
• Arm: 1
• Actual Duration (Months): 28

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Hypertension; Metabolic Disorder	Drug: losartan potassium (+) hydrochlorothiazide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1738 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Hemoglobin A1c Between 52 Weeks and Baseline [52 Weeks - Baseline]

   Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.

2. Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments [52 Weeks - Baseline]

   Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.

Secondary Outcome Measures

1. Target Blood Pressure [52 Weeks]

   Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks

2. Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.

3. Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.

Other Outcome Measures

1. Change in Waist Circumference Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute change in Waist Circumference between baseline and 52 week assessments

2. Change in Body Mass Index Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute change in Body Mass Index Baseline and 52 week assessments

3. Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Percent Change in LDL-C Between Baseline and 52 week assessments: 100% x [(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)].

4. Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Percent Change in HDL-C Between Baseline and 52 week assessments: 100% x [(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)].

5. Percent Change in Triglycerides Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x [(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)].

6. Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x [(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)].

7. Absolute Change in Uric Acid Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute Change in Uric Acid Between Baseline and 52 week assessments: Uric Acid 52 weeks - Uric Acid Baseline.

8. Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments [52 Weeks - Baseline]

   Absolute Change in C Reactive Protein Between Baseline and 52 week assessments: C Reactive Protein 52 weeks - C Reactive Protein Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00546052
• Other Study ID Numbers: 0954A-331; MK0954A-331; 2007_030
• First Posted: Oct 18, 2007
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Metabolic Syndrome; Metabolic Diseases; Losartan; Hydrochlorothiazide

Study Results

Participant Flow

Recruitment Details	First Patient In: 12-Sep-2005 Last Patient In: 29-Dec-2006 Last Patient Last Visit: 31-Jan-08 Total number of Sites (General Practitioners and Family Physicians in Canada): 209
Pre-assignment Detail	24 patients not included in the Intention to Treat (ITT) analysis because they did not receive study medication and had no follow up visits. Total ITT population = 1714.

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients could be titrated up from Cozaar 50 mg to Cozaar 100mg to losartan 100 mg + Hydrochlorothiazide 12.5 mg and losartan 100mg/ Hydrochlorothiazide 25 mg, in sequence at any subsequent visits only if needed to obtain Blood Pressure under 140/90 mm Hg.
Period Title: Overall Study
STARTED	1738
Week 4	1714
Week 8	1680
Week 12	1650
Week 32	1583
Week 52	1511
COMPLETED	1511
NOT COMPLETED	227

Baseline Characteristics

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients could be titrated up from Cozaar 50 mg to Cozaar 100mg to losartan 100 mg + Hydrochlorothiazide 12.5 mg and losartan 100mg/ Hydrochlorothiazide 25 mg, in sequence at any subsequent visits only if needed to obtain Blood Pressure under 140/90 mm Hg.
Overall Participants	1714
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.93 (11.29)
Age, Customized (participants) [Number]
<=45.00	326 19%
45.01 - 52.00	359 20.9%
52.01 - 58.00	356 20.8%
58.01 - 65.00	346 20.2%
>=65.00	326 19%
Missing	1 0.1%
Sex: Female, Male (Count of Participants)
Female	734 42.8%
Male	980 57.2%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	1451 84.7%
Black	32 1.9%
Asian	200 11.7%
Native American	11 0.6%
Other	19 1.1%
Missing	1 0.1%
Body Mass Index (Kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/m2]	33.23 (5.59)
C-Reactive Protein (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	5.4 (8.8)
Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	90.54 (8.16)
Fasting Blood Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.7 (0.7)
Heart Rate (Beats per Minute (BPM)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Beats per Minute (BPM)]	75 (8.0)
Hemoglobin A1c (Percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent]	5.71 (0.59)
High Density Lipoprotein-C (mol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mol/L]	1.23 (0.33)
Low Density Lipoprotein-C (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	3.17 (0.93)
Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	148.22 (10.72)
Total Cholesterol (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.36 (1.05)
Triglycerides (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	2.16 (1.16)
Uric Acid (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	365.8 (85.4)
Weight (Kilograms (Kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (Kg)]	92.5 (18.1)

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin A1c Between 52 Weeks and Baseline
Description	Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Median (Standard Deviation) [Percent]	0.04 (0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is + 0.5%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	() 95%; -0.02 to 0.06
	Parameter Dispersion	Type: Standard Deviation; Value: 0.74
	Estimation Comments

2. Primary Outcome

Title	Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments
Description	Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [mmol/L]	0.02 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is + 0.5mmol/L.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	() 95%; 0.01 to 0.07
	Parameter Dispersion	Type: Standard Deviation; Value: 0.62
	Estimation Comments

3. Secondary Outcome

Title	Target Blood Pressure
Description	Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

ITT and Per Protocol

Arm/Group Title	Overall Total	Overall Intend to Treat	Overall Per Protocol
Arm/Group Description	All patients enrolled (signed the informed consent).	All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	All patients completing the 52 week study follow up.
Measure Participants	1738	1714	1511
Achieved Target Blood Pressure	1200 70%	1200 NaN	1200 NaN
Did NOT achieve target Blood Pressure	538 31.4%	514 NaN	311 NaN

4. Secondary Outcome

Title	Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments
Description	Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [mm Hg]	-16.95 (13.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is 0 mm Hg
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.95
	Confidence Interval	() 95%; -17.62 to -16.27
	Parameter Dispersion	Type: Standard Deviation; Value: 13.34
	Estimation Comments

5. Secondary Outcome

Title	Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments
Description	Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [mm Hg]	-9.84 (8.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is 0 mm Hg.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.84
	Confidence Interval	() 95%; -10.29 to -9.39
	Parameter Dispersion	Type: Standard Deviation; Value: 8.39
	Estimation Comments

6. Other Pre-specified Outcome

Title	Change in Waist Circumference Between Baseline and 52 Week Assessments
Description	Absolute change in Waist Circumference between baseline and 52 week assessments
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [cm]	-1.28 (5.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 5.4
	Estimation Comments

7. Other Pre-specified Outcome

Title	Change in Body Mass Index Between Baseline and 52 Week Assessments
Description	Absolute change in Body Mass Index Baseline and 52 week assessments
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [Kg/m2]	-7.3 (5.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 5.20
	Estimation Comments

8. Other Pre-specified Outcome

Title	Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments
Description	Percent Change in LDL-C Between Baseline and 52 week assessments: 100% x [(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)].
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [Percent Change]	-1.49 (32.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.084
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 32.1
	Estimation Comments

9. Other Pre-specified Outcome

Title	Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments
Description	Percent Change in HDL-C Between Baseline and 52 week assessments: 100% x [(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)].
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [Percent Change]	0.21 (17.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.654
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 18.0
	Estimation Comments

10. Other Pre-specified Outcome

Title	Percent Change in Triglycerides Between Baseline and 52 Week Assessments
Description	Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x [(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)].
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Median (Standard Deviation) [Percent Change]	1.09 (43.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.336
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 43.5
	Estimation Comments

11. Other Pre-specified Outcome

Title	Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments
Description	Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x [(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)].
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [Percent Change]	-2.98 (16.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 17.0
	Estimation Comments

12. Other Pre-specified Outcome

Title	Absolute Change in Uric Acid Between Baseline and 52 Week Assessments
Description	Absolute Change in Uric Acid Between Baseline and 52 week assessments: Uric Acid 52 weeks - Uric Acid Baseline.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [mmol/L]	-19.17 (63.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 63.8
	Estimation Comments

13. Other Pre-specified Outcome

Title	Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments
Description	Absolute Change in C Reactive Protein Between Baseline and 52 week assessments: C Reactive Protein 52 weeks - C Reactive Protein Baseline.
Time Frame	52 Weeks - Baseline

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Losartan +/- Hydrochlorothiazide
Arm/Group Description	Patients that completed 52 weeks of treatment and were >= 80% compliant with the study medication.
Measure Participants	1511
Mean (Standard Deviation) [mg/L]	-0.36 (8.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Losartan +/- Hydrochlorothiazide
	Comments	Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.613
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 8.7
	Estimation Comments

Adverse Events

Arm/Group Title	Overall ITT
Arm/Group Description
All Cause Mortality
	Overall ITT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Overall ITT
	Affected / at Risk (%)	# Events
Total	35/1714 (2%)
Cardiac disorders
Acute coronary syndrome	1/1714 (0.1%)
Atrial flutter	1/1714 (0.1%)
Cardiomyopathy	1/1714 (0.1%)
Infarction	1/1714 (0.1%)
Single Vessel Disease	1/1714 (0.1%)
Gastrointestinal disorders
Gastric Ulcer	1/1714 (0.1%)
Nausea	1/1714 (0.1%)
Vomiting	1/1714 (0.1%)
Ulcer Bleeding Gastric	1/1714 (0.1%)
General disorders
Chest Pain	1/1714 (0.1%)
Death	2/1714 (0.1%)
Immune system disorders
Anaphylactic shock	1/1714 (0.1%)
Anaphylaxis	1/1714 (0.1%)
Infections and infestations
Pneumonia	1/1714 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture	1/1714 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	3/1714 (0.2%)
Lymphoma grade IV	1/1714 (0.1%)
Nervous system disorders
Cerebral vascular accident	3/1714 (0.2%)
Multiple sclerosis aggravated	1/1714 (0.1%)
Numbness of Upper Arm	1/1714 (0.1%)
Subarachnoid Hemorrhage	1/1714 (0.1%)
Psychiatric disorders
Acute depression	1/1714 (0.1%)
Renal and urinary disorders
Acute renal insufficiency	1/1714 (0.1%)
Respiratory, thoracic and mediastinal disorders
Bronchitis asthmatic	1/1714 (0.1%)
Surgical and medical procedures
Cardiac catheterization	1/1714 (0.1%)
Hip Replacement	2/1714 (0.1%)
Ileostomy	1/1714 (0.1%)
Rotator Cuff Repair	1/1714 (0.1%)
Vascular disorders
Atherosclerotic cardiovascular disease	1/1714 (0.1%)
Superficial Femoral Arterial Stenosis	1/1714 (0.1%)
Other (Not Including Serious) Adverse Events
	Overall ITT
	Affected / at Risk (%)	# Events
Total	198/1714 (11.6%)
Infections and infestations
Sinusitis	19/1714 (1.1%)
Investigations
Blood Glucose Increased (per investigator's clinical judgment)	17/1714 (1%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	54/1714 (3.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	23/1714 (1.3%)
Nervous system disorders
Dizziness	35/1714 (2%)
Headache	21/1714 (1.2%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	29/1714 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.