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Efficacy of a Combination of Amlodipine/Valsartan on 24H Blood Pressure Control With One Nocturnal or Diurnal Intake a Day

Phase 4
Completed
Conditions
Hypertension
Interventions
Registration Number
NCT00700271
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study was a multicenter, randomized, PROBE-type (prospective, randomized, open label, blinded end-point) study of 12 weeks duration comprising four visits, carried out in patients with essential arterial hypertension not controlled on four weeks treatment with amlodipine 5 mg alone.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
478
Inclusion Criteria
  • Age >= 18 years
  • Essential uncontrolled or naive hypertensive patients (SBP ≥= 140 mmHG, DBP - >/=90 mm Hg, or SBP >= 130 mmHg, DBP >= 80 mmHg if diabetes or renal impairment) except patients treated with amlodipine, or intolerant of ARBs and/or calcium channel blockers.
Exclusion Criteria
  • Severe hypertension : SBP >= 180 mmHg, DBP >= 110mmHg
  • Pregnancy
  • Allergia to ARBs and/or to calcium channel blockers
  • Antihypertensive tritherapy at V1
  • History of heart failure, pectoris angina, stroke, myocardial infarction
  • Diabetes type I
  • Renal impairment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Evening IntakeValsartanAfter randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Morning IntakeAmlodipineAfter randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Morning IntakeValsartanAfter randomization, participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the morning between 6-10 am. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Evening IntakeAmlodipineAfter randomization participants received a single daily oral dose of 5 mg amlodipine and 160 mg valsartan free combination therapy, taken in the evening between 6-10 pm. At week 4, uncontrolled patients (msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg or msSBP \>= 130 mmHg and/or msDBP \>= 80 mmHg in the case of diabetes or renal insufficiency measured by using conventional methods) received amlodipine/valsartan 10/160 mg for 4 additional weeks. Patients who were controlled at Week 4 (msSBP \< 140 mmHg and msDBP \< 90 mmHg or msSBP \< 130 mmHg and msDBP \< 80 mmHg in the case of diabetes or renal insufficiency) continued their amlodipine/valsartan 5/160 mg treatment for the remaining 4 weeks of the study.
Primary Outcome Measures
NameTimeMethod
Absolute Reduction From Baseline in 24-hour Mean Systolic Blood Pressure (SBP) on Ambulatory Blood Pressure MonitoringBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Secondary Outcome Measures
NameTimeMethod
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood PressureBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for five minutes; the investigator then took three blood pressure and one pulse rate reading. The measurements were recorded at 1-2 minute intervals. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure MonitoringBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure MonitoringBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Absolute Reduction From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure MonitoringBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Percentage of Participants With Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 135/85 mmHg at Endpoint With Ambulatory Blood Pressure MonitoringVisit 4 (week 8)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Percentage of Participants With Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 120/70 mmHg at Endpoint With Ambulatory Blood Pressure MonitoringVisit 4 (week 8)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure MonitoringBaseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit 2 was carried out prior to randomization and the first dose of the amlodipine/valsartan combination study therapy. ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood PressureScreening visit (Week -4, prior to 4-week open-label screening phase) and Week 8 (after 8 weeks of combination therapy)

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for five minutes; the investigator then took three blood pressure and one pulse rate reading. The measurements were recorded at 1-2 minute intervals. Covariates included baseline level, country, up-titration + treatment\*country and treatment\*up-titration interactions in case statistically significant at a 0.10 level.

Percentage of Participants With 24-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 125/80 mmHg at Endpoint With Ambulatory Blood Pressure MonitoringVisit 4 (week 8)

Ambulatory Blood Pressure Monitoring (ABPM) over a 30-hour period was carried out in all patients at two visits during the study, 72 hours before visit 2 (baseline) and visit 4 (week 8). ABPM for visit four began after 12 weeks of treatment and before the last office blood pressure was taken.

Percentage of Participants With Controlled Office Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) at EndpointVisit 4 (week 8)

At each of the office visits, blood pressure was recorded in the morning between 08.00 and 11.00, before any antihypertensive treatment was taken. The patient remained in a sitting position for 5 minutes; the investigator then took 3 blood pressure and 1 pulse rate reading. The measurements were recorded at 1-2 minute intervals. BP Control is defined as msSBP/msDBP \<149/90 mmHg and/or \<130/80 mmHg if diabetes or renal insufficiency (RI).

Trial Locations

Locations (2)

Investigative sites in Tunisia

🇹🇳

Tunisia, Tunisia

Investigative sites in France

🇫🇷

Paris, France

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