Hypertension
Conditions
Brief summary
To evaluate the blood pressure efficacy between losartan and valsartan at equivalent dosage during a 3 months treatment.
Interventions
losartan potassium 50 mg/12.5 Hydrochlorothiazide (HCTZ) titrated as needed to losartan potassium 100 mg/25 mg Hydrochlorothiazide
DRUGComparator: Valsartan (+) Hydrochlorothiazide
Valsartan 80 mg/ Hydrochlorothiazide 12.5 mg/day titrated as needed to valsartan 160 mg/25 mg Hydrochlorothiazide
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* An Adult Patient 18 to 75 Years Of Age * Patient with essential hypertension receiving an antihypertensive agent in monotherapy for at least 4 weeks for whom the antihypertensive agent can (and will) be discontinued and whose blood pressure is not controlled: * Either systolic or diastolic blood pressure \> 140/90 mm Hg up to 180/110 mm Hg (inclusive) * Either systolic or diastolic blood pressure \> 130/80 mm Hg up to 160/100 mm Hg (inclusive) for diabetic patients * Patient is male or a female who is highly unlikely to conceive as she falls into one of the categories listed below: * Surgically sterilized female * Postmenopausal female \> 45 years of age with \> 2 years since her last menses * Non-sterilized pre-menopausal female who agrees to: (1) use 2 adequate methods of contraception to prevent pregnancy \[either 2 barrier methods or a barrier method plus a hormonal method\]; or (2) abstain from heterosexual activity throughout the study starting with Visit 1 and for 14 days after the last dose of study medication; or (3) only engage in heterosexual activity with surgically sterilized male partner(s) throughout the study starting with Visit 1 and for 14 days after the last dose of study medication * Patient judged to be in otherwise good, stable health on the basis of medical history and physical examination
Exclusion criteria
* Known secondary hypertension of any aetiology (e.g., uncorrected renal artery stenosis, malignant hypertension, or hypertensive encephalopathy) * Patient Needing An Initiation Of A Lipid Lowering Agent Or A Modification Of His Lipid Therapy At Visit 1 Or During The Study Period (12 Weeks) * Patient taking allopurinol * Patient Previously Shown To Be Intolerant To Any Component Of Losartan Valsartan, Or HCTZ Or With A Documented History Of Angioedema/Anaphylaxis * Patient With Confirmed Clinically Significant Renal Or Hepatic Dysfunction And/Or Electrolyte Imbalance Laboratory Test Within The Last 3 Months Prior To Visit 1: Serum Creatinine \> 130 Umol/L Or Creatinine Clearance \< 45 Ml/Min, Aspartate transaminase (AST) \> 2 Times Above The Normal Range, Alanine transaminase (ALT) \> 2 Times Above The Normal Range, Serum Potassium \< 3.5 Or \> 5.5 Meq/L * Patient with osteoarthritis who has undergone hip or knee replacement within the last 4 months * Patient with chronic inflammatory conditions such as rheumatoid arthritis, lupus, inflammatory bowel disease and those that need a chronic inflammatory therapy such as prednisone or other steroid agents * Patient with symptomatic heart failure (classes 3 and 4) * Patient with a history of stroke within the last 6 months * Patient with coronary heart disease: has undergone percutaneous coronary angioplasty, has had coronary artery bypass, has had past myocardial infarction, all that occurred less than 6 months prior to visit 1 or has unstable angina * Patient having participated in an investigational drug program in the last 30 days (prior to Visit 1) * Unable or unwilling to comply with the protocol, therefore likely to leave the trial before its completion * Patient intends to move or to vacation away from home during the course of the study which would interfere with the scheduled visits.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Systolic Blood Pressure From Baseline to Week 12 | Baseline and Week 12 |
| Change in Diastolic Blood Pressure From Baseline to Week 12 | Baseline and Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Target Blood Pressure at Week 6 | Week 6 | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) at week 6 |
| Number of Patients Achieving Target Blood Pressure at Week 12 | 12 Weeks | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) at week 12 |
| Time to Achieve Target Blood Pressure | 12 weeks | Time to achieve the target blood pressure (\<140/90 mmHg and \<130/80 mmHg for diabetics) |
| Change in Uric Acid From Baseline to Week 6 | Baseline and Week 6 | — |
| Change in Systolic Blood Pressure From Baseline to Week 6 | Baseline and Week 6 | — |
| Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 6 | Baseline and Week 6 | — |
| Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 12 | Baseline and Week 12 | — |
| Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 6 | Baseline and Week 6 | — |
| Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 12 | Baseline and Week 12 | — |
| Change in Uric Acid From Baseline to Week 12 | Baseline and Week 12 | — |
| Change in Diastolic Blood Pressure From Baseline to Week 6 | Baseline and Week 6 | — |
Participant flow
Recruitment details
First patient in: MAY-04-2007 Last patient out: APRIL-16-2009 Total number of sites: 163 sites in Canada
Participants by arm
| Arm | Count |
|---|---|
| Losartan 50 mg/HCTZ 12.5 mg Patients could be titrated up from losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg to losartan 100 mg/HCTZ 25 mg only if needed to achieve target blood pressure.
416 number of patients that received at least one dose of study medication and had 1 follow-up visit (intent-to-treat population \[ITT\]) | 416 |
| Valsartan 80 mg/HCTZ 12.5 mg Patients could be titrated up from valsartan 80 mg/HCTZ 12.5 mg to valsartan 160 mg/HCTZ 25 mg only if needed to achieve target blood pressure.
373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (intent-to-treat population \[ITT\]) | 373 |
| Total | 789 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 16 |
| Overall Study | Dyspnea | 1 | 0 |
| Overall Study | Elevated Creatinine and Potassium levels | 0 | 1 |
| Overall Study | Hip Replacement | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 15 |
| Overall Study | Missing | 14 | 7 |
| Overall Study | Missing Cooperation | 1 | 0 |
| Overall Study | Patient's Decision | 0 | 1 |
| Overall Study | Per Data Query, Less Than 4 Wks Coversyl | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Serious Adverse Event | 1 | 1 |
| Overall Study | Suicide | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 |
Baseline characteristics
| Characteristic | Total | Losartan 50 mg/HCTZ 12.5 mg | Valsartan 80 mg/HCTZ 12.5 mg |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 10.71 | 58.7 years STANDARD_DEVIATION 11.11 | 58.3 years STANDARD_DEVIATION 10.26 |
| Race/Ethnicity, Customized Asian | 63 participants | 34 participants | 29 participants |
| Race/Ethnicity, Customized Black | 21 participants | 8 participants | 13 participants |
| Race/Ethnicity, Customized Caucasian | 690 participants | 364 participants | 326 participants |
| Race/Ethnicity, Customized East Indian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized From Middle East | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Native | 8 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized Unknown | 3 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 377 Participants | 197 Participants | 180 Participants |
| Sex: Female, Male Male | 412 Participants | 219 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 425 | 57 / 383 |
| serious Total, serious adverse events | 11 / 425 | 5 / 383 |
Outcome results
Primary
Change in Diastolic Blood Pressure From Baseline to Week 12
Time frame: Baseline and Week 12
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 371 and 331 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Diastolic Blood Pressure From Baseline to Week 12 | -10.6 mm Hg | Standard Deviation 9.28 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Diastolic Blood Pressure From Baseline to Week 12 | -10.5 mm Hg | Standard Deviation 9.58 |
p-value: 0.935ANOVA
Primary
Change in Systolic Blood Pressure From Baseline to Week 12
Time frame: Baseline and Week 12
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 371 and 331 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Systolic Blood Pressure From Baseline to Week 12 | -19.9 mm Hg | Standard Deviation 13.79 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Systolic Blood Pressure From Baseline to Week 12 | -20.8 mm Hg | Standard Deviation 13.61 |
p-value: 0.395ANOVA
Secondary
Change in Diastolic Blood Pressure From Baseline to Week 6
Time frame: Baseline and Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 392 and 344 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Diastolic Blood Pressure From Baseline to Week 6 | -8.4 mm Hg | Standard Deviation 9.35 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Diastolic Blood Pressure From Baseline to Week 6 | -9.1 mm Hg | Standard Deviation 9.16 |
p-value: 0.343ANOVA
Secondary
Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 12
Time frame: Baseline and Week 12
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 279 and 254 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 12 | -0.7 IU/L | Standard Deviation 21.44 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 12 | -0.0 IU/L | Standard Deviation 24.45 |
p-value: 0.725ANOVA
Secondary
Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 6
Time frame: Baseline and Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 300 and 273 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 6 | -1.8 IU/L | Standard Deviation 21.2 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 6 | -0.1 IU/L | Standard Deviation 24.71 |
p-value: 0.386ANOVA
Secondary
Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 12
Time frame: Baseline and Week 12
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 279 and 255 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 12 | -0.3 umol/L | Standard Deviation 8.05 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 12 | 0.5 umol/L | Standard Deviation 7.2 |
p-value: 0.218ANOVA
Secondary
Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 6
Time frame: Baseline and Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 304 and 272 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 6 | 0.8 mg/L | Standard Deviation 26.21 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 6 | 0.6 mg/L | Standard Deviation 6.6 |
p-value: 0.899ANOVA
Secondary
Change in Systolic Blood Pressure From Baseline to Week 6
Time frame: Baseline and Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 392 and 344 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Systolic Blood Pressure From Baseline to Week 6 | -16.7 mm Hg | Standard Deviation 14.7 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Systolic Blood Pressure From Baseline to Week 6 | -18.2 mm Hg | Standard Deviation 13.84 |
p-value: 0.153ANOVA
Secondary
Change in Uric Acid From Baseline to Week 12
Time frame: Baseline and Week 12
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 286 and 253 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Uric Acid From Baseline to Week 12 | -0.4 umol/L | Standard Deviation 57.02 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Uric Acid From Baseline to Week 12 | 29.9 umol/L | Standard Deviation 64.79 |
p-value: <0.001ANOVA
Secondary
Change in Uric Acid From Baseline to Week 6
Time frame: Baseline and Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 298 and 269 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Change in Uric Acid From Baseline to Week 6 | 0.3 umol/L | Standard Deviation 53.12 |
| Valsartan 80 mg/HCTZ 12.5 mg | Change in Uric Acid From Baseline to Week 6 | 21.7 umol/L | Standard Deviation 55.09 |
p-value: <0.001ANOVA
Secondary
Number of Patients Achieving Target Blood Pressure at Week 12
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) at week 12
Time frame: 12 Weeks
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 372 and 332 patients at week 12 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 12 | Achieved Target Blood Pressure | 278 Patients |
| Losartan 50 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 12 | Did Not Achieve Target Blood Pressure | 94 Patients |
| Valsartan 80 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 12 | Achieved Target Blood Pressure | 253 Patients |
| Valsartan 80 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 12 | Did Not Achieve Target Blood Pressure | 79 Patients |
p-value: 0.662Fisher Exact
Secondary
Number of Patients Achieving Target Blood Pressure at Week 6
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) at week 6
Time frame: Week 6
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 393 and 345 patients at week 6 for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 6 | Achieved Target Blood Pressure | 253 Patients |
| Losartan 50 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 6 | Did Not Achieve Target Blood Pressure | 140 Patients |
| Valsartan 80 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 6 | Achieved Target Blood Pressure | 241 Patients |
| Valsartan 80 mg/HCTZ 12.5 mg | Number of Patients Achieving Target Blood Pressure at Week 6 | Did Not Achieve Target Blood Pressure | 104 Patients |
p-value: 0.118Fisher Exact
Secondary
Time to Achieve Target Blood Pressure
Time to achieve the target blood pressure (\<140/90 mmHg and \<130/80 mmHg for diabetics)
Time frame: 12 weeks
Population: 416 and 373 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 406 and 360 patients for Losartan 50/HCTZ 12.5mg and Valsartan 80/HCTZ 12.5mg respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg/HCTZ 12.5 mg | Time to Achieve Target Blood Pressure | 62.3 Days | Standard Deviation 1.44 |
| Valsartan 80 mg/HCTZ 12.5 mg | Time to Achieve Target Blood Pressure | 57.3 Days | Standard Deviation 1.24 |
p-value: 0.02Log Rank