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

Conditions

Hypertension

Keywords

Hypertension, ambulatory blood pressure monitoring

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.

Related papers

No related papers found yet.

Interventions

DRUGAmlodipine

5 mg or 10 mg tablets.

DRUGValsartan

160 mg capsules.

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

* 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

Design outcomes

Primary

Measure	Time frame	Description
Absolute Reduction From Baseline in 24-hour Mean Systolic Blood Pressure (SBP) on Ambulatory Blood Pressure Monitoring	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

Measure	Time frame	Description
Absolute Reduction From Baseline in Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring	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.
Absolute Reduction From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring	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.
Absolute Reduction From Baseline in 6-hour Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring	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.
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week 0 and Week 8 in Office Blood Pressure	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.
Absolute Reduction From Baseline in Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) on Ambulatory Blood Pressure Monitoring	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.
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	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.
Percentage of Participants With Diurnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 135/85 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring	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.
Percentage of Participants With Nocturnal Mean Systolic Blood Pressure (SBP)/Diastolic Blood Pressure (DBP) < 120/70 mmHg at Endpoint With Ambulatory Blood Pressure Monitoring	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.
Percentage of Participants With Controlled Office Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) at Endpoint	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).
Mean Seated Systolic Blood Pressure (msSBP)/Mean Seated Diastolic Blood Pressure (msDBP) Variation Between Week -4 to Week 8 in Office Blood Pressure	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.

Countries

France, Tunisia

Participant flow

Pre-assignment details

Eligible patients entered a 4-week open-label amlodipine screening phase with amlodipine 5 mg taken orally once a day. At the end of the screening phase, patients whose blood pressure was not adequately controlled (defined as SBP/DBP \>= 125/80 mmHg 24-hr mean) on ambulatory blood pressure monitoring were randomized to one of two treatment groups.

Participants by arm

Arm	Count
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.	242
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.	237
Total	479

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Administrative Reasons	1	0
Overall Study	Adverse Event	4	6
Overall Study	Lost to Follow-up	2	2
Overall Study	Protocol Violation	1	0
Overall Study	Withdrawal by Subject	6	4

Baseline characteristics

Characteristic	Morning Intake	Evening Intake	Total
Age Continuous	55.8 years STANDARD_DEVIATION 9.89	56.2 years STANDARD_DEVIATION 9.59	56.0 years STANDARD_DEVIATION 9.74
Sex: Female, Male Female	114 Participants	111 Participants	225 Participants
Sex: Female, Male Male	128 Participants	126 Participants	254 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 278	0 / 268
serious Total, serious adverse events	2 / 278	2 / 268

Outcome results

Primary

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.

Time frame: Baseline (Week 0, after completion of screening period) and Week 8 (after 8 weeks of combination therapy)