Hypertension
Conditions
Brief summary
After a 4 week placebo period, patients were randomized to Placebo or Losartan 50 mg arms, after 6 weeks non-responders were up titrated to 100 mg losartan for the remaining 6 weeks. This study evaluated if losartan is more effective than placebo in lowering sitting diastolic blood pressure and is well tolerated in patients with mild to moderate hypertension.
Interventions
DRUGlosartan potassium
50 mg Losartan (MK0954) tablet taken once daily for 12 weeks.
50 mg tablet of Losartan (MK0954) taken once daily for 6 weeks, Non-responders will then have the dose up titrated to 100 mg for remaining 6 weeks.
DRUGComparator: Placebo
Placebo to Losartan
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has been diagnosed with mild to moderate hypertension (SDBP 95-115 mm Hg) * Patient has no medical problems or treatments that might effect their blood pressure
Exclusion criteria
* Pregnant or lactating females * Patient has secondary hypertension or malignant hypertension * Sitting systolic blood pressure \> 210 mm Hg * History of stroke * History of myocardial infarction with in past year * Current or prior history of heart failure * Known hypersensitivity to losartan * Prior exposure to losartan * Patients known to be HIV positive * Patient is abusing or has abused alcohol or other drugs within the past 4 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | At baseline and at 12 weeks (24 hours post dose) | Mean change from baseline in trough (24 hours post dose) SiDBP at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | 24 hours post dose at Week 6 | Patients with trough SiDBP \<90 mm Hg were in Category I, ≥90 but decreased at least 10 mm Hg were in Category II, and ≥90 and decreased less than 10 mm Hg were in Category III. |
| Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | 24 hours post dose at Week 12 | Patients with trough SiDBP \<90 mm Hg were in Category I, ≥90 but decreased at least 10 mm Hg were in Category II, and ≥90 and decreased less than 10 mm Hg were in Category III. |
| Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | At baseline and at 6 weeks (24 hours post dose) | Mean change from baseline in trough (24 hours post dose) SiDBP at Week 6 |
| Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | At baseline and at 6 weeks (24 hours post dose) | Mean change from baseline in peak (6 hours post dose) SiDBP at Week 6 |
| Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | At baseline and at 12 weeks (6 hours post dose) | Mean change from baseline in peak (6 hours post dose) SiDBP at Week 12 |
Participant flow
Recruitment details
Patients were recruited at 22 sites in the United States. Prime Therapy Period: December, 1991 to August, 1992.
Pre-assignment details
Patients could be randomized after the 4-week placebo baseline period if their mean sitting diastolic blood pressure (SiDBP) was 95-115 mm Hg and ≤7 mm Hg from the mean SiDBP after 2 weeks of placebo therapy
Participants by arm
| Arm | Count |
|---|---|
| Placebo Losartan placebo orally once daily for 12 weeks | 116 |
| Losartan 50 mg Losartan 50 mg orally once daily for 12 weeks | 127 |
| Losartan 50/100 mg Losartan orally once daily for 12 weeks, initiated as 50 mg and titrated to 100 mg for nonresponders (SiDBP ≥90 mm Hg) after 6 weeks | 123 |
| Total | 366 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 7 |
| Overall Study | Lack of Efficacy | 9 | 6 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Patient uncooperative | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Losartan 50 mg | Losartan 50/100 mg | Total |
|---|---|---|---|---|
| Age Continuous | 53.8 years | 53.2 years | 55.1 years | 54.0 years |
| Race/Ethnicity, Customized Black | 17 participants | 14 participants | 16 participants | 47 participants |
| Race/Ethnicity, Customized Caucasian | 92 participants | 104 participants | 101 participants | 297 participants |
| Race/Ethnicity, Customized Hispanic | 7 participants | 8 participants | 4 participants | 19 participants |
| Race/Ethnicity, Customized Indian | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Oriental | 0 participants | 0 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 42 Participants | 44 Participants | 45 Participants | 131 Participants |
| Sex: Female, Male Male | 74 Participants | 83 Participants | 78 Participants | 235 Participants |
| Sitting Diastolic Blood Pressure (SiDBP) | 101.3 mm Hg | 102.2 mm Hg | 102.2 mm Hg | 101.9 mm Hg |
Outcome results
Primary
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12
Mean change from baseline in trough (24 hours post dose) SiDBP at Week 12
Time frame: At baseline and at 12 weeks (24 hours post dose)
Population: The primary analysis employed an all patients treated approach that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -4.3 mm Hg | Standard Deviation 6.7 |
| Losartan 50 mg | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -7.9 mm Hg | Standard Deviation 7.6 |
| Losartan 50/100 mg | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -8.6 mm Hg | Standard Deviation 7.7 |
Secondary
Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12
Patients with trough SiDBP \<90 mm Hg were in Category I, ≥90 but decreased at least 10 mm Hg were in Category II, and ≥90 and decreased less than 10 mm Hg were in Category III.
Time frame: 24 hours post dose at Week 12
Population: An all patients treated approach was employed that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category II | 12 Participants |
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category I | 19 Participants |
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category III | 83 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category II | 18 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category I | 40 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category III | 67 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category I | 37 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category III | 57 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 12 | Category II | 24 Participants |
Secondary
Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6
Patients with trough SiDBP \<90 mm Hg were in Category I, ≥90 but decreased at least 10 mm Hg were in Category II, and ≥90 and decreased less than 10 mm Hg were in Category III.
Time frame: 24 hours post dose at Week 6
Population: An all patients treated approach was employed that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category II | 8 Participants |
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category I | 14 Participants |
| Placebo | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category III | 92 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category II | 20 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category I | 37 Participants |
| Losartan 50 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category III | 68 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category I | 37 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category III | 60 Participants |
| Losartan 50/100 mg | Categories of Hypertensive Response in Trough Diastolic Blood Pressure (SiDBP) at Week 6 | Category II | 21 Participants |
Secondary
Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 12
Mean change from baseline in peak (6 hours post dose) SiDBP at Week 12
Time frame: At baseline and at 12 weeks (6 hours post dose)
Population: The primary analysis employed an all patients treated approach that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -4.7 mm Hg | Standard Deviation 7.9 |
| Losartan 50 mg | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -9.5 mm Hg | Standard Deviation 9.2 |
| Losartan 50/100 mg | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 12 | -10.1 mm Hg | Standard Deviation 8.6 |
Secondary
Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 6
Mean change from baseline in peak (6 hours post dose) SiDBP at Week 6
Time frame: At baseline and at 6 weeks (24 hours post dose)
Population: The primary analysis employed an all patients treated approach that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -4.1 mm Hg | Standard Deviation 6.9 |
| Losartan 50 mg | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -9.7 mm Hg | Standard Deviation 8.7 |
| Losartan 50/100 mg | Mean Change From Baseline in Peak Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -8.9 mm Hg | Standard Deviation 8.7 |
Secondary
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 6
Mean change from baseline in trough (24 hours post dose) SiDBP at Week 6
Time frame: At baseline and at 6 weeks (24 hours post dose)
Population: An all patients treated approach was employed that included patients with at least one treatment period measurement. The last measurements of withdrawn patients were carried forward to subsequent timepoints. Missing data were estimated by carrying forward data from the last visit (excluding baseline) at which it was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -3.5 mm Hg | Standard Deviation 5.8 |
| Losartan 50 mg | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -6.9 mm Hg | Standard Deviation 7 |
| Losartan 50/100 mg | Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 6 | -7.9 mm Hg | Standard Deviation 7.1 |