Hypertension
Conditions
Brief summary
This is a 16-week study to evaluate high systolic and diastolic blood pressure following treatment in obese, hypertensive, adult patients.
Interventions
DRUGComparator: losartan +/- HCTZ
Placebo to losartan once daily for 4 weeks in run-in period. Then, losartan 50 mg for 4 weeks, then titrate to losartan 100 mg at Week 4, then titrate to losartan 100 mg + hydrochlorothiazide (HCTZ) 12.5 mg at Week 8, and finally titrate to losartan 100 mg + HCTZ 25 mg at Week 12. Duration of treatment is approximately 16 weeks.
DRUGComparator: Placebo
Placebo to losartan once daily for 4 weeks in run-in period. Then, placebo to losartan or losartan/HCTZ once daily for approximately 16 weeks.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Obese male and female patients, ages 21-75 years, with high blood pressure
Exclusion criteria
* Patients cannot have any other severe cardiac conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
| Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
| Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
| Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 12 | At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
| Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 16 | At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
| Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 16 | At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM) | Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline. |
Participant flow
Recruitment details
Patients were recruited at 51 sites in the United States. Prime Therapy Period: April 2006 to February 2007
Pre-assignment details
Prior antihypertensive medications were withdrawn/ tapered before patients entered the 4-week placebo run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Losartan Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg | 127 |
| Placebo Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg | 134 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lack of Efficacy | 3 | 11 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other | 7 | 3 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | Losartan |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 9.7 | 50.8 years STANDARD_DEVIATION 10 | 50.1 years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Black | 29 participants | 51 participants | 22 participants |
| Race/Ethnicity, Customized Caucasian | 87 participants | 171 participants | 84 participants |
| Race/Ethnicity, Customized Hispanic American | 16 participants | 36 participants | 20 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 77 Participants | 156 Participants | 79 Participants |
| Sex: Female, Male Male | 57 Participants | 105 Participants | 48 Participants |
| Sitting Diastolic Blood Pressure (SiDBP) | 99.0 mm Hg STANDARD_DEVIATION 4 | 99.0 mm Hg STANDARD_DEVIATION 4.1 | 99.1 mm Hg STANDARD_DEVIATION 4.2 |
| Sitting Systolic Blood Pressure (SiSBP) | 152.4 mm Hg STANDARD_DEVIATION 9 | 152.0 mm Hg STANDARD_DEVIATION 8.6 | 151.6 mm Hg STANDARD_DEVIATION 8.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 127 | 7 / 134 |
| serious Total, serious adverse events | 1 / 127 | 1 / 134 |
Outcome results
Primary
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -12.9 mm Hg | Standard Error 0.8 |
| Placebo | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -7.1 mm Hg | Standard Error 0.8 |
Primary
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 16
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 16 | -14.1 mm Hg | Standard Error 0.9 |
| Placebo | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 16 | -6.0 mm Hg | Standard Error 0.9 |
Primary
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8
Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | -9.7 mm Hg | Standard Error 0.8 |
| Placebo | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8 | -6.9 mm Hg | Standard Error 0.8 |
Primary
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 12
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 12. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 12 | -16.7 mm Hg | Standard Error 1.3 |
| Placebo | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 12 | -6.8 mm Hg | Standard Error 1.3 |
Primary
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 16
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 16. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 16 | -19.1 mm Hg | Standard Error 1.3 |
| Placebo | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 16 | -6.4 mm Hg | Standard Error 1.3 |
Primary
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8
Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.
Time frame: At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
Population: An all patients treated approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | -12.1 mm Hg | Standard Error 1.2 |
| Placebo | Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8 | -6.8 mm Hg | Standard Error 1.2 |