Hypertension
Conditions
Brief summary
The primary objective of this study is to evaluate efficacy, arterial stiffness measured by Pulse Wave Velocity (PWV) of Losartan potassium group compared to Carvedilol group after 24 weeks of treatment in patients with the essential hypertension.
Interventions
DRUGlosartan potassium
Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg/ hydrochlorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)
DRUGComparator: carvedilol
Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)
DRUGComparator: losartan (+) hydrochlorothiazide (HCTZ)
Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg/ hydrochlorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)
DRUGComparator: carvedilol (+) hydrochlorothiazide
Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan)
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
* Male or Female adults, 18 years or over * Essential Hypertension with mean SBP (systolic blood pressure) ≥ 140 mm Hg or mean DBP (diastolic blood pressure) ≥ 90 mm Hg\* when blood pressure is measured at Visit 1(week -2) and at Visit 2(week 0). If diabetes patients, mean SBP ≥ 130 mm Hg or mean DBP ≥ 80 mm Hg (Mean of blood pressure values measured consecutively at least 2 minutes apart) * Patient who is willing to, and is able to sign the informed consent form
Exclusion criteria
* Patient Is Pregnant Or Breastfeeding, Or Expecting To Conceive Within The Projected Duration Of The Study * Patient Has Known Or Suspected Secondary Hypertension Of Any Etiology * Patient has history of malignant hypertension * Patient has history of cerebrovascular accident (cerebral infarction) or myocardiac infarction within the last 6 months * Patient takes antihypertensive drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | Baseline and 24 Weeks | Analysis was performed in the modified intention to treat (mITT) population. |
| PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | Baseline and 24 Weeks | Analysis was performed in the per protocol (PP) population which additionally excludes certain protocol violations as described in the analysis plan. |
Secondary
| Measure | Time frame |
|---|---|
| Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | Baseline and 24 weeks |
| Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | Baseline and 24 weeks |
Participant flow
Recruitment details
7 centers participated in this study (7 medical centers of university). FPE (First patient enrolled): Feb-2008, FPI (First patient in): Feb-2008, LPO (Last patient out): Sep-2009
Participants by arm
| Arm | Count |
|---|---|
| Losartan Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan). | 101 |
| Carvedilol Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or
Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan). | 100 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Blood Pressure control failure | 2 | 1 |
| Overall Study | Contraindicated medication administered | 0 | 1 |
| Overall Study | Inclusion/exclusion criteria not met | 3 | 2 |
| Overall Study | IP administration violation | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Losartan | Carvedilol | Total |
|---|---|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 9.3 | 50.1 years STANDARD_DEVIATION 10.2 | 49.6 years STANDARD_DEVIATION 9.7 |
| Age, Customized >= 18 to < 65 years | 96 participants | 91 participants | 187 participants |
| Age, Customized >=65 years | 5 participants | 9 participants | 14 participants |
| DBP (diastolic blood pressure) | 96.4 mm Hg STANDARD_DEVIATION 8.8 | 96.4 mm Hg STANDARD_DEVIATION 8.3 | 96.4 mm Hg STANDARD_DEVIATION 8.5 |
| Height | 164.9 Centimeters STANDARD_DEVIATION 7.8 | 163.3 Centimeters STANDARD_DEVIATION 9.2 | 164.1 Centimeters STANDARD_DEVIATION 8.5 |
| Pulse | 71.8 BPM (beats per minute) STANDARD_DEVIATION 10 | 72.3 BPM (beats per minute) STANDARD_DEVIATION 10 | 72.0 BPM (beats per minute) STANDARD_DEVIATION 10 |
| PWV (pulse wave velocity) | 7.6 meters/second STANDARD_DEVIATION 1.4 | 7.7 meters/second STANDARD_DEVIATION 1.4 | 7.6 meters/second STANDARD_DEVIATION 1.4 |
| SBP (systolic blood pressure) | 150.6 mm Hg STANDARD_DEVIATION 11 | 152.7 mm Hg STANDARD_DEVIATION 12.1 | 151.6 mm Hg STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 63 Participants | 57 Participants | 120 Participants |
| Sex: Female, Male Male | 38 Participants | 43 Participants | 81 Participants |
| Weight | 70.9 Kilograms STANDARD_DEVIATION 10.6 | 69.9 Kilograms STANDARD_DEVIATION 13.2 | 70.4 Kilograms STANDARD_DEVIATION 12 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 101 | 51 / 100 |
| serious Total, serious adverse events | 5 / 101 | 6 / 100 |
Outcome results
Primary
Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Analysis was performed in the modified intention to treat (mITT) population.
Time frame: Baseline and 24 Weeks
Population: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94). Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | 0.28 meters/second | Standard Deviation 1.29 |
| Carvedilol | Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -0.12 meters/second | Standard Deviation 1.55 |
Comparison: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94).95% CI: [-0.83, 0.01]
Primary
PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Analysis was performed in the per protocol (PP) population which additionally excludes certain protocol violations as described in the analysis plan.
Time frame: Baseline and 24 Weeks
Population: Participants for analysis was per protocol (Number of patients: Losartan group was 54, Carvedilol group was 67). Missing data were imputed by the last observation carried forward (LOCF) technique. For the primary efficacy endpoints, Per protocol analysis approach was supplementary used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | 0.16 meters/second | Standard Deviation 1.25 |
| Carvedilol | PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -0.20 meters/second | Standard Deviation 1.5 |
Comparison: Participants for analysis was per protocol (Number of patients: Losartan group was 54, Carvedilol group was 67). For the primary efficacy endpoints, Per protocol analysis approach was supplementary used.95% CI: [-0.86, 0.15]
Secondary
Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Time frame: Baseline and 24 weeks
Population: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94) Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -8.43 mm Hg | Standard Deviation 9.29 |
| Carvedilol | Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -7.81 mm Hg | Standard Deviation 9.61 |
p-value: 0.6574t-test, 2 sided
Secondary
Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug
Time frame: Baseline and 24 weeks
Population: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94) Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -15.08 mm Hg | Standard Deviation 14.59 |
| Carvedilol | Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug | -14.81 mm Hg | Standard Deviation 15.38 |
p-value: 0.9032t-test, 2 sided