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

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of a Combination of Amlodipine / Valsartan on Blood Pressure Control, With One Nocturnal or Diurnal Intake a Day, in Ambulatory Blood Pressure Monitoring Setting, in Essential Uncontrolled Hypertensive Patients With Amlodipine 5mg ; The ExPERT Study

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Amlodipine
* Drug: Valsartan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Morning Intake<br>After 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. | Drug: Amlodipine<br>* 5 mg or 10 mg tablets.<br>Drug: Valsartan<br>* 160 mg capsules.<br>|
| Experimental: Evening Intake<br>After 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. | Drug: Amlodipine<br>* 5 mg or 10 mg tablets.<br>Drug: Valsartan<br>* 160 mg capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Reduction From Baseline in 24-hour Mean Systolic Blood Pressure (SBP) on Ambulatory Blood Pressure Monitoring | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 
| Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 
| Absolute Reduction From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 
| Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 
| Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood Pressure | 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. | Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy) | 
| Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood Pressure | 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. | Screening visit (Week -4, prior to 4-week open-label screening phase) and Week 8 (after 8 weeks of combination therapy) | 
| Percentage of Participants With 24-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 125/80 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring | 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. | Visit 4 (week 8) | 
| Percentage of Participants With Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 135/85 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring | 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. | Visit 4 (week 8) | 
| Percentage of Participants With Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 120/70 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring | 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. | Visit 4 (week 8) | 
| Percentage of Participants With Controlled Office Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) at Endpoint | 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). | Visit 4 (week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, ambulatory blood pressure monitoring