Hypertension, Metabolic Disorder
Conditions
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.
Interventions
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.
Sponsors
Organon and Co
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c Between 52 Weeks and Baseline | 52 Weeks - Baseline | Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Target Blood Pressure | 52 Weeks | 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 | 52 Weeks - Baseline | Absolute change in Systolic Blood Pressure between baseline and 52 week assessments. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 \[(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)\]. |
| 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 \[(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)\]. |
| 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 \[(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)\]. |
| 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. |
| 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. |
| Change in Waist Circumference Between Baseline and 52 Week Assessments | 52 Weeks - Baseline | Absolute change in Waist Circumference between baseline and 52 week assessments |
| 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 |
| 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 \[(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)\]. |
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Losartan +/- Hydrochlorothiazide 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. | 1,714 |
| Total | 1,714 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 47 |
| Overall Study | Lost to Follow-up | 144 |
| Overall Study | Non Compliance | 7 |
| Overall Study | Protocol Violation | 9 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | Losartan +/- Hydrochlorothiazide |
|---|---|
| Age, Continuous | 54.93 Years STANDARD_DEVIATION 11.29 |
| Age, Customized <=45.00 | 326 participants |
| Age, Customized 45.01 - 52.00 | 359 participants |
| Age, Customized 52.01 - 58.00 | 356 participants |
| Age, Customized 58.01 - 65.00 | 346 participants |
| Age, Customized >=65.00 | 326 participants |
| Age, Customized Missing | 1 participants |
| Body Mass Index | 33.23 Kg/m2 STANDARD_DEVIATION 5.59 |
| C-Reactive Protein | 5.4 mg/L STANDARD_DEVIATION 8.8 |
| Diastolic Blood Pressure | 90.54 mm Hg STANDARD_DEVIATION 8.16 |
| Fasting Blood Glucose | 5.7 mmol/L STANDARD_DEVIATION 0.7 |
| Heart Rate | 75 Beats per Minute (BPM) STANDARD_DEVIATION 8 |
| Hemoglobin A1c | 5.71 Percent STANDARD_DEVIATION 0.59 |
| High Density Lipoprotein-C | 1.23 mol/L STANDARD_DEVIATION 0.33 |
| Low Density Lipoprotein-C | 3.17 mmol/L STANDARD_DEVIATION 0.93 |
| Race/Ethnicity, Customized Asian | 200 participants |
| Race/Ethnicity, Customized Black | 32 participants |
| Race/Ethnicity, Customized Caucasian | 1451 participants |
| Race/Ethnicity, Customized Missing | 1 participants |
| Race/Ethnicity, Customized Native American | 11 participants |
| Race/Ethnicity, Customized Other | 19 participants |
| Sex: Female, Male Female | 734 Participants |
| Sex: Female, Male Male | 980 Participants |
| Systolic Blood Pressure | 148.22 mm Hg STANDARD_DEVIATION 10.72 |
| Total Cholesterol | 5.36 mmol/L STANDARD_DEVIATION 1.05 |
| Triglycerides | 2.16 mmol/L STANDARD_DEVIATION 1.16 |
| Uric Acid | 365.8 mmol/L STANDARD_DEVIATION 85.4 |
| Weight | 92.5 Kilograms (Kg) STANDARD_DEVIATION 18.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 198 / 1,714 |
| serious Total, serious adverse events | 35 / 1,714 |
Outcome results
Primary
Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments
Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments | 0.02 mmol/L | Standard Deviation 0.74 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is + 0.5mmol/L.p-value: 0.99995% CI: [0.01, 0.07]t-test, 1 sided
Primary
Change in Hemoglobin A1c Between 52 Weeks and Baseline
Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Hemoglobin A1c Between 52 Weeks and Baseline | 0.04 Percent | Standard Deviation 0.62 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is + 0.5%.p-value: 0.99995% CI: [-0.02, 0.06]t-test, 1 sided
Secondary
Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments
Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments | -9.84 mm Hg | Standard Deviation 8.93 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is 0 mm Hg.p-value: <0.00195% CI: [-10.29, -9.39]t-test, 2 sided
Secondary
Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments
Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments | -16.95 mm Hg | Standard Deviation 13.34 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null hypothesis value is 0 mm Hgp-value: <0.00195% CI: [-17.62, -16.27]t-test, 2 sided
Secondary
Target Blood Pressure
Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks
Time frame: 52 Weeks
Population: ITT and Per Protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Target Blood Pressure | Achieved Target Blood Pressure | 1200 Participants |
| Losartan +/- Hydrochlorothiazide | Target Blood Pressure | Did NOT achieve target Blood Pressure | 538 Participants |
| Overall Intend to Treat | Target Blood Pressure | Achieved Target Blood Pressure | 1200 Participants |
| Overall Intend to Treat | Target Blood Pressure | Did NOT achieve target Blood Pressure | 514 Participants |
| Overall Per Protocol | Target Blood Pressure | Achieved Target Blood Pressure | 1200 Participants |
| Overall Per Protocol | Target Blood Pressure | Did NOT achieve target Blood Pressure | 311 Participants |
Other Pre-specified
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.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments | -0.36 mg/L | Standard Deviation 8.66 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.613t-test, 2 sided
Other Pre-specified
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.
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Absolute Change in Uric Acid Between Baseline and 52 Week Assessments | -19.17 mmol/L | Standard Deviation 63.84 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.001t-test, 2 sided
Other Pre-specified
Change in Body Mass Index Between Baseline and 52 Week Assessments
Absolute change in Body Mass Index Baseline and 52 week assessments
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Body Mass Index Between Baseline and 52 Week Assessments | -7.3 Kg/m2 | Standard Deviation 5.2 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: <0.001t-test, 2 sided
Other Pre-specified
Change in Waist Circumference Between Baseline and 52 Week Assessments
Absolute change in Waist Circumference between baseline and 52 week assessments
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Change in Waist Circumference Between Baseline and 52 Week Assessments | -1.28 cm | Standard Deviation 5.44 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: <0.001t-test, 2 sided
Other Pre-specified
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 \[(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)\].
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments | 0.21 Percent Change | Standard Deviation 17.96 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.654t-test, 2 sided
Other Pre-specified
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 \[(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)\].
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments | -1.49 Percent Change | Standard Deviation 32.1 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.084t-test, 2 sided
Other Pre-specified
Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments
Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x \[(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)\].
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments | -2.98 Percent Change | Standard Deviation 16.97 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.001t-test, 2 sided
Other Pre-specified
Percent Change in Triglycerides Between Baseline and 52 Week Assessments
Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x \[(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)\].
Time frame: 52 Weeks - Baseline
Population: Per Protocol
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Losartan +/- Hydrochlorothiazide | Percent Change in Triglycerides Between Baseline and 52 Week Assessments | 1.09 Percent Change | Standard Deviation 43.54 |
Comparison: Single Cohort Study. Statistical Analysis is based on change from baseline. Null Hypothesis value is 0.p-value: 0.336t-test, 2 sided