Hypertension
Conditions
Brief summary
To evaluate the effectiveness of diet management with a losartan based titration regimen versus losartan based titration regimen alone on blood pressure reduction in hypertensive patients.
Interventions
DRUGlosartan potassium (+ hydrochlorothiazide [HCTZ] + calcium channel blocker [CCB])
Losartan 50 mg or 100 mg once daily for 40 weeks with sequential titration including HCTZ 12.5 mg or 25 mg and CCB only as needed to achieve target blood pressure, as follows: Patients with mild-moderate hypertension, uncontrolled hypertension on monotherapy, or diabetes: * Losartan 50 mg * Losartan 100 mg * Losartan 100 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 25 mg * Losartan 100 mg/HCTZ 25 mg + CCB Patients with severe hypertension: * Losartan 50 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 12.5 mg * Losartan 100 mg/HCTZ 25 mg * Losartan 100 mg/HCTZ 25 mg + CCB * Losartan 100 mg/HCTZ 25 mg + increasing CCB
BEHAVIORALLow Salt Diet
Low-salt intake diet (Dietary Approaches to Stop Hypertension \[DASH\]) including: * Healthy diet * Reduction in sodium intake to less than 2300 mmol/day * Low alcohol consumption (less than 2 standard drinks/day)
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non Diabetic, Newly Diagnosed And Untreated For Mild To Moderate Hypertension (blood pressure \> 161; \< 221; 140/90 mm Hg But \< 180/110 mm Hg) * Non diabetic, newly diagnosed and untreated for severe hypertension (blood pressure \> 180/110 mm Hg but \< 200/120 mm Hg); Patients who are asymptomatic with no evidence of significant end organ damage including direct pressure effects can be included. Patients in an urgency/emergency state are to be excluded * Or Diabetic, Newly Diagnosed With Hypertension And Untreated With Mild To Moderate Hypertension (blood pressure \> 161;\< 221; 130/80 mm Hg But \< 160/100 mm Hg); Or Patient Receiving One Antihypertensive Agent (Monotherapy Only) Used To Treat Hypertension For At Least 4 Weeks And Whose Blood Pressure Is Not Controlled: blood pressure \> 161;\< 221; 140/90 mm Hg But \< 160/100 mm Hg Or For Diabetic And/Or Coronary Artery Disease Patients: blood pressure \> 161;\< 221; 130/80 mm Hg But \> 161;\< 221; 150/90 mm Hg * The Antihypertensive Agent Will Need To Be Discontinued Prior To Starting Study Drug
Exclusion criteria
* Known Secondary Hypertension Of Any Aetiology (E.G., Uncorrected Renal Artery Stenosis, Malignant Hypertension, Hypertensive Encephalopathy. Patient With Symptomatic Heart Failure (Classes 3 And 4). Patient With A Prior Myocardial Infarction Or Stroke Within The Last 6 Months * Patient Has Undergone Percutaneous Coronary Angioplasty, Has Had Coronary Artery Bypass Within The Last 6 Months Or Has Unstable Angina * Patient With Anuria Or Confirmed Clinically Significant Renal Or Hepatic Dysfunction (Taken From Current/Past Medical Records) And/Or Electrolyte Imbalance Laboratory Test Within The Last 3 Months Prior To Visit 1: Serum Creatinine \> 130 Ìmol/L Or Creatinine Clearance \< 45 Ml/Min, Ast \> 3 Times Above The Normal Range, Alt \> 3 Times Above The Normal Range, Serum Potassium \< 3.5 Or \> 5.5 Meq/L * Significant Liver Or Respiratory Disease, Cancer Or Other concomitant Disease That Is Likely To Affect Life Expectancy Of The Patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | 14 Weeks | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment |
| Change in Systolic Blood Pressure From Baseline to Week 14 | 14 Weeks | — |
| Change in Diastolic Blood Pressure From Baseline to Week 14 | 14 Weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure From Baseline to Week 6 | 6 Weeks | — |
| Change in Diastolic Blood Pressure From Baseline to Week 6 | 6 Weeks | — |
| Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | 6 Weeks | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 6 weeks of treatment |
| Change in Diastolic Blood Pressure From Baseline to Week 10 | 10 Weeks | — |
| Time to Achieve the Target Blood Pressure From Baseline | 14 Weeks | Time to achieve the target blood pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics). |
| Change in Systolic Blood Pressure From Baseline to Week 10 | 10 Weeks | — |
| Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | 10 Weeks | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 10 weeks of treatment |
| Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | 40 Weeks | Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 40 weeks of treatment |
Participant flow
Recruitment details
First patient in: FEB-05-2008 Last patient out: JAN-15-2010 Total number of sites: 109 sites in Canada
Participants by arm
| Arm | Count |
|---|---|
| Losartan-Based Regimen Alone (L Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.
The Baseline Measures are reported for the Intent-to-treat (ITT) population (i.e. took at least one dose of the study medication and returned for one follow-up visit). | 463 |
| Diet Management and Losartan-Based Regimen (DML Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
The Baseline Measures are reported for the Intent-to-treat (ITT) population (i.e. took at least one dose of the study medication and returned for one follow-up visit). | 400 |
| Total | 863 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 13 |
| Overall Study | Clinic closed | 6 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Dietician consultation >30 days | 1 | 9 |
| Overall Study | Erectile dysfunction | 0 | 1 |
| Overall Study | Home monitoring off meds | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 52 | 30 |
| Overall Study | No follow-up data | 33 | 18 |
| Overall Study | Non compliant | 4 | 0 |
| Overall Study | Patient moved | 3 | 2 |
| Overall Study | Protocol Violation | 5 | 5 |
| Overall Study | Reason missing | 2 | 0 |
| Overall Study | Screening failures | 19 | 17 |
| Overall Study | Site 212 removal | 19 | 13 |
| Overall Study | Unable to attend visit | 3 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 9 |
Baseline characteristics
| Characteristic | Total | Losartan-Based Regimen Alone (L Group) | Diet Management and Losartan-Based Regimen (DML Group) |
|---|---|---|---|
| Age, Continuous | 55.38 years STANDARD_DEVIATION 11.76 | 56.05 years STANDARD_DEVIATION 11.54 | 54.59 years STANDARD_DEVIATION 11.98 |
| Cardiovascular Risk High | 204 Participants | 112 Participants | 92 Participants |
| Cardiovascular Risk Low | 434 Participants | 218 Participants | 216 Participants |
| Cardiovascular Risk Medium | 155 Participants | 94 Participants | 61 Participants |
| Cardiovascular Risk Missing | 8 Participants | 4 Participants | 4 Participants |
| Cardiovascular Risk Not Available | 62 Participants | 35 Participants | 27 Participants |
| Diastolic Blood Pressure | 91.02 mm Hg STANDARD_DEVIATION 9.57 | 90.67 mm Hg STANDARD_DEVIATION 9.19 | 91.43 mm Hg STANDARD_DEVIATION 9.98 |
| Race/Ethnicity, Customized Asian | 58 participants | 38 participants | 20 participants |
| Race/Ethnicity, Customized Black | 13 participants | 9 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Native Indian | 5 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Other | 11 participants | 7 participants | 4 participants |
| Race/Ethnicity, Customized White | 773 participants | 404 participants | 369 participants |
| Sex: Female, Male Female | 447 Participants | 239 Participants | 208 Participants |
| Sex: Female, Male Male | 416 Participants | 224 Participants | 192 Participants |
| Systolic Blood Pressure | 151.17 mm Hg STANDARD_DEVIATION 11.64 | 151.23 mm Hg STANDARD_DEVIATION 10.8 | 151.11 mm Hg STANDARD_DEVIATION 12.55 |
| Weight | 87.16 Kilograms STANDARD_DEVIATION 20.13 | 85.41 Kilograms STANDARD_DEVIATION 19.95 | 89.17 Kilograms STANDARD_DEVIATION 20.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 531 | 46 / 453 |
| serious Total, serious adverse events | 13 / 531 | 10 / 453 |
Outcome results
Primary
Change in Diastolic Blood Pressure From Baseline to Week 14
Time frame: 14 Weeks
Population: 463 and 400 - 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 357 patients at week 14 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Diastolic Blood Pressure From Baseline to Week 14 | -10.19 mm Hg | Standard Deviation 9.33 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Diastolic Blood Pressure From Baseline to Week 14 | -12.05 mm Hg | Standard Deviation 9.5 |
p-value: 0.058Regression, Linear
Primary
Change in Systolic Blood Pressure From Baseline to Week 14
Time frame: 14 Weeks
Population: 463 and 400 - 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 357 patients at week 14 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Systolic Blood Pressure From Baseline to Week 14 | -21.01 mm Hg | Standard Deviation 14.11 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Systolic Blood Pressure From Baseline to Week 14 | -22.74 mm Hg | Standard Deviation 15.81 |
p-value: 0.507Regression, Linear
Primary
Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment
Time frame: 14 Weeks
Population: 463 and 400 - 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 357 patients at week 14 for L group and DML group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | Achieve Target Blood Pressure | 276 Participants |
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | Did not Achieve Target Blood Pressure | 116 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | Achieve Target Blood Pressure | 270 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline | Did not Achieve Target Blood Pressure | 87 Participants |
p-value: 0.118Fisher Exact
Secondary
Change in Diastolic Blood Pressure From Baseline to Week 10
Time frame: 10 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 399 and 370 patients at week 10 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Diastolic Blood Pressure From Baseline to Week 10 | -9.48 mm Hg | Standard Deviation 8.8 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Diastolic Blood Pressure From Baseline to Week 10 | -11.42 mm Hg | Standard Deviation 9.45 |
p-value: 0.026Regression, Linear
Secondary
Change in Diastolic Blood Pressure From Baseline to Week 6
Time frame: 6 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 431 and 383 patients at week 6 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Diastolic Blood Pressure From Baseline to Week 6 | -8.34 mm Hg | Standard Deviation 9.29 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Diastolic Blood Pressure From Baseline to Week 6 | -9.76 mm Hg | Standard Deviation 9.82 |
p-value: 0.064Regression, Linear
Secondary
Change in Systolic Blood Pressure From Baseline to Week 10
Time frame: 10 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 399 and 370 patients at week 10 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Systolic Blood Pressure From Baseline to Week 10 | -19.11 mm Hg | Standard Deviation 14.87 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Systolic Blood Pressure From Baseline to Week 10 | -20.95 mm Hg | Standard Deviation 16.24 |
p-value: 0.262Regression, Linear
Secondary
Change in Systolic Blood Pressure From Baseline to Week 6
Time frame: 6 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 431 and 383 patients at week 6 for L group and DML group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Change in Systolic Blood Pressure From Baseline to Week 6 | -16.81 mm Hg | Standard Deviation 14.92 |
| Diet Management and Losartan-Based Regimen (DML Group) | Change in Systolic Blood Pressure From Baseline to Week 6 | -18.85 mm Hg | Standard Deviation 16.18 |
p-value: 0.158Regression, Linear
Secondary
Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 10 weeks of treatment
Time frame: 10 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 399 and 370 patients at week 10 for L group and DML group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | Achieve Target Blood Pressure | 257 Participants |
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | Did not Achieve Target Blood Pressure | 142 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | Achieve Target Blood Pressure | 254 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline | Did not Achieve Target Blood Pressure | 116 Participants |
p-value: 0.122Fisher Exact
Secondary
Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 40 weeks of treatment
Time frame: 40 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 351 and 331 patients at week 40 for L group and DML group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | Achieve Target Blood Pressure | 264 Participants |
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | Did not Achieve Target Blood Pressure | 87 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | Achieve Target Blood Pressure | 240 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline | Did not Achieve Target Blood Pressure | 91 Participants |
p-value: 0.434Fisher Exact
Secondary
Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline
Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 6 weeks of treatment
Time frame: 6 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 431 and 383 patients at week 6 for L group and DML group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | Achieve Target Blood Pressure | 239 Participants |
| Losartan-Based Regimen Alone (L Group) | Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | Did not Achieve Target Blood Pressure | 192 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | Achieve Target Blood Pressure | 231 Participants |
| Diet Management and Losartan-Based Regimen (DML Group) | Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline | Did not Achieve Target Blood Pressure | 152 Participants |
p-value: 0.092Fisher Exact
Secondary
Time to Achieve the Target Blood Pressure From Baseline
Time to achieve the target blood pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics).
Time frame: 14 Weeks
Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 437 and 386 patients for L group and DML group respectively.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Losartan-Based Regimen Alone (L Group) | Time to Achieve the Target Blood Pressure From Baseline | 7.43 Weeks |
| Diet Management and Losartan-Based Regimen (DML Group) | Time to Achieve the Target Blood Pressure From Baseline | 6.57 Weeks |
p-value: 0.212Log Rank