Hypertension
Conditions
Brief summary
The purpose of this study was to compare the antihypertensive efficacy of different doses of losartan compared to placebo and enalapril, in patients with supine diastolic blood pressure of 100-115 mmHg.
Interventions
DRUGlosartan potassium
losartan oral capsule (10, 25, 50, 100 or 150 mg) once daily for 8 weeks
DRUGPlacebo
Placebo capsule to losartan
DRUGEnalapril
Enalapril 20 mg oral tablet taken once daily for 8 weeks
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, with supine diastolic blood pressure of 100 to 115 mmHg * Patient has no active medical problems other than essential hypertension that might affect blood pressure * Patient has received no drug therapy that might affect blood pressure
Exclusion criteria
* Prior exposure to losartan * History of stroke * History of myocardial infarction * Atrial flutter or atrial fibrillation * History of congestive Heart failure * Known Sensitivity to ACE inhibitors * Known positive test for HIV/AIDS or Hepatitis B * Patient is being treated for acute ulcer disease * History of chronic liver disease * Actively treated diabetes mellitis * Any known bleeding or platelet disorder * Absence of one kidney * Women of childbearing potential or who are breastfeeding * Patient is abusing or has a history of alcoholism or drug addiction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | 24 hours post dose at Baseline and Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | 24 hours post dose at Week 8 | Patients in Category I (defined as excellent in protocol) if SuDBP was \<90 mmHg, Category II (defined as good in protocol) if SuDBP was ≥90 but decreased at least 10 mmHg, or Category III (defined as fair or inadequate in protocol) if SuDBP was ≥90 and decreased less than 10 mmHg. |
| Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | 6 hours post dose at Baseline and 8 weeks | — |
Participant flow
Recruitment details
Patients were recruited at 28 sites in the United States. Primary Therapy Period: December, 1990-August, 1991
Pre-assignment details
Patients could be randomized after the 4-week placebo baseline period if their mean supine diastolic blood pressure (SuDBP) was 100-115 mmHg and ≤7 mmHg from the mean SuDBP after 2 weeks of placebo therapy, or after a 2-week placebo baseline period if 2 sets of SuDBP data were within 100-115 mmHg, ≥3 days apart and differed by ≤7 mmHg.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Losartan and Enalapril placebo orally once daily for 8 weeks | 78 |
| Losartan 10 mg Losartan 10 mg orally once daily for 8 weeks | 80 |
| Losartan 25 mg Losartan 25 mg orally once daily for 8 weeks | 82 |
| Losartan 50 mg Losartan 50 mg orally once daily for 8 weeks | 79 |
| Losartan 100 mg Losartan 100 mg orally once daily for 8 weeks | 90 |
| Losartan 150 mg Losartan 150 mg orally once daily for 8 weeks | 84 |
| Enalapril 20 Enalapril 20 mg orally once daily for 8 weeks | 83 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 2 | 1 | 1 | 4 | 2 |
| Overall Study | Lack of Efficacy | 3 | 5 | 2 | 0 | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 1 | 1 | 0 | 1 |
| Overall Study | Patient Uncooperative | 2 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 0 | 6 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Losartan 10 mg | Losartan 25 mg | Losartan 50 mg | Losartan 100 mg | Losartan 150 mg | Enalapril 20 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 11.6 | 53.9 years STANDARD_DEVIATION 12.3 | 52.8 years STANDARD_DEVIATION 12.2 | 52.8 years STANDARD_DEVIATION 10.3 | 54.0 years STANDARD_DEVIATION 10.2 | 53.9 years STANDARD_DEVIATION 10.8 | 51.9 years STANDARD_DEVIATION 11.1 | 53.1 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity Black | 5 participants | 10 participants | 14 participants | 11 participants | 17 participants | 11 participants | 7 participants | 75 participants |
| Race/Ethnicity Caucasian | 64 participants | 60 participants | 63 participants | 57 participants | 66 participants | 64 participants | 64 participants | 438 participants |
| Race/Ethnicity Hispanic | 9 participants | 9 participants | 5 participants | 11 participants | 7 participants | 8 participants | 10 participants | 59 participants |
| Race/Ethnicity Other | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 31 Participants | 29 Participants | 27 Participants | 26 Participants | 31 Participants | 22 Participants | 27 Participants | 193 Participants |
| Sex: Female, Male Male | 47 Participants | 51 Participants | 55 Participants | 53 Participants | 59 Participants | 62 Participants | 56 Participants | 383 Participants |
| SuDBP | 103.3 mmHg STANDARD_DEVIATION 3.8 | 104.3 mmHg STANDARD_DEVIATION 3.9 | 103.3 mmHg STANDARD_DEVIATION 3.7 | 104.0 mmHg STANDARD_DEVIATION 3.7 | 104.1 mmHg STANDARD_DEVIATION 4.2 | 103.4 mmHg STANDARD_DEVIATION 3.4 | 103.1 mmHg STANDARD_DEVIATION 3.7 | 103.7 mmHg STANDARD_DEVIATION 3.8 |
Outcome results
Primary
Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8
Time frame: 24 hours post dose at Baseline and Week 8
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 Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -5.6 mm Hg | Standard Deviation 7.8 |
| Losartan 10 mg | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -7.9 mm Hg | Standard Deviation 7.6 |
| Losartan 25 mg | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -6.8 mm Hg | Standard Deviation 7.9 |
| Losartan 50 mg | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -10.1 mm Hg | Standard Deviation 7 |
| Losartan 100 mg | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -9.9 mm Hg | Standard Deviation 6.9 |
| Losartan 150 mg | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -9.7 mm Hg | Standard Deviation 8 |
| Enalapril 20 | Mean Change From Baseline in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -11.2 mm Hg | Standard Deviation 6.7 |
Secondary
Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8
Patients in Category I (defined as excellent in protocol) if SuDBP was \<90 mmHg, Category II (defined as good in protocol) if SuDBP was ≥90 but decreased at least 10 mmHg, or Category III (defined as fair or inadequate in protocol) if SuDBP was ≥90 and decreased less than 10 mmHg.
Time frame: 24 hours post dose at Week 8
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 Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 54 Participants |
| Placebo | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 14 Participants |
| Placebo | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 10 Participants |
| Losartan 10 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 44 Participants |
| Losartan 10 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 17 Participants |
| Losartan 10 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 19 Participants |
| Losartan 25 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 54 Participants |
| Losartan 25 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 7 Participants |
| Losartan 25 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 21 Participants |
| Losartan 50 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 39 Participants |
| Losartan 50 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 24 Participants |
| Losartan 50 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 15 Participants |
| Losartan 100 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 19 Participants |
| Losartan 100 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 41 Participants |
| Losartan 100 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 29 Participants |
| Losartan 150 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 44 Participants |
| Losartan 150 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 28 Participants |
| Losartan 150 mg | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 12 Participants |
| Enalapril 20 | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category II | 16 Participants |
| Enalapril 20 | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category I | 35 Participants |
| Enalapril 20 | Categories of Antihypertensive Response in Trough Supine Diastolic Blood Pressure (SuDBP) at Week 8 | Category III | 31 Participants |
Secondary
Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8
Time frame: 6 hours post dose at Baseline and 8 weeks
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 Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -4.7 mm Hg | Standard Deviation 8.7 |
| Losartan 10 mg | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -7.3 mm Hg | Standard Deviation 9.4 |
| Losartan 25 mg | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -9.9 mm Hg | Standard Deviation 8.5 |
| Losartan 50 mg | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -11.9 mm Hg | Standard Deviation 9.2 |
| Losartan 100 mg | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -10.4 mm Hg | Standard Deviation 8.9 |
| Losartan 150 mg | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -13.1 mm Hg | Standard Deviation 9 |
| Enalapril 20 | Mean Change From Baseline in Peak Supine Diastolic Blood Pressure (SuDBP) at Week 8 | -16.2 mm Hg | Standard Deviation 10.4 |