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

• ClinicalTrials.gov Identifier: NCT00700271
• Recruitment Status: Completed
• First Posted: June 18, 2008
• Results First Posted: January 6, 2011
• Last Update Posted: May 19, 2011
• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Amlodipine; Drug: Valsartan	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 478 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2007
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Morning Intake; 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; 5 mg or 10 mg tablets.; Drug: Valsartan; 160 mg capsules.
Experimental: Evening Intake; 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; 5 mg or 10 mg tablets.; Drug: Valsartan; 160 mg capsules.

Outcome Measures

Primary Outcome Measures :

1. Absolute Reduction From Baseline in 24-hour Mean Systolic Blood Pressure (SBP) on Ambulatory Blood Pressure Monitoring [ Time Frame: Baseline (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 :

1. Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring [ Time Frame: Baseline (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.
2. Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring [ Time Frame: Baseline (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.
3. Absolute Reduction From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring [ Time Frame: Baseline (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.
4. Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring [ Time Frame: Baseline (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.
5. Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood Pressure [ Time Frame: Baseline (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.
6. Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood Pressure [ Time Frame: Screening 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.
7. 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 [ Time Frame: Visit 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.
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 [ Time Frame: Visit 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.
9. Percentage of Participants With Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 120/70 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring [ Time Frame: Visit 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.
10. Percentage of Participants With Controlled Office Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) at Endpoint [ Time Frame: Visit 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Investigative sites in France

Paris, France

Tunisia

Investigative sites in Tunisia

Tunisia, Tunisia

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Principal Investigator: Roland Asmar; principle investigator; Institut cardiovasculaire 75016 Paris

More Information

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00700271
• Other Study ID Numbers: CVAA489AFR01
• First Posted: June 18, 2008
• Results First Posted: January 6, 2011
• Last Update Posted: May 19, 2011
• Last Verified: May 2011

Keywords provided by Novartis:

Hypertension; ambulatory blood pressure monitoring

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Amlodipine; Valsartan; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists