Trial Outcomes & Findings for Valsartan Intensified Primary Care Reduction of Blood Pressure Study (NCT NCT00902304)
NCT ID: NCT00902304
Last Updated: 2012-12-04
Results Overview
BP target groups were: \<= 125/75mmHg, \<= 130/80mmHg and \<= 140/90mmHg. The BP target was based on the patient's clinical risk profile as specified by National Heart Foundation of Australia guidelines.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
2337 participants
Primary outcome timeframe
26 weeks
Results posted on
2012-12-04
Participant Flow
2337 patients were enrolled. 2185 received study medication during the 4 week run-in period. 1562 patients were randomized.
Participant milestones
| Measure |
Usual Care
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
524
|
360
|
678
|
|
Overall Study
COMPLETED
|
466
|
289
|
568
|
|
Overall Study
NOT COMPLETED
|
58
|
71
|
110
|
Reasons for withdrawal
| Measure |
Usual Care
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
10
|
25
|
|
Overall Study
Investigator discretion
|
3
|
5
|
13
|
|
Overall Study
Lost to Follow-up
|
7
|
7
|
7
|
|
Overall Study
Protocol Violation
|
9
|
18
|
20
|
|
Overall Study
Withdrawal by Subject
|
32
|
22
|
43
|
|
Overall Study
includes pregnancy
|
3
|
9
|
2
|
Baseline Characteristics
Valsartan Intensified Primary Care Reduction of Blood Pressure Study
Baseline characteristics by cohort
| Measure |
Usual Care
n=524 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Total
n=1562 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
59 years
STANDARD_DEVIATION 12 • n=5 Participants
|
59 years
STANDARD_DEVIATION 12 • n=7 Participants
|
59 years
STANDARD_DEVIATION 12 • n=5 Participants
|
59 years
STANDARD_DEVIATION 12 • n=4 Participants
|
|
Sex: Female, Male
Female
|
201 Participants
n=5 Participants
|
138 Participants
n=7 Participants
|
260 Participants
n=5 Participants
|
599 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
323 Participants
n=5 Participants
|
222 Participants
n=7 Participants
|
418 Participants
n=5 Participants
|
963 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Last Observation Carried Forward (LOCF) imputation technique is used for this analysis.
BP target groups were: \<= 125/75mmHg, \<= 130/80mmHg and \<= 140/90mmHg. The BP target was based on the patient's clinical risk profile as specified by National Heart Foundation of Australia guidelines.
Outcome measures
| Measure |
Usual Care
n=504 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=339 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=649 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Percentage of Patients Who Have Achieved Their Pre-specified (Individualized National Heart Foundation of Australia Criteria) Blood Pressure (BP) Target
|
27.4 percentage of participants
|
33.0 percentage of participants
|
37.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Last Observation Carried Forward (LOCF) imputation technique is used for this analysis.
The visit window was from 22 to 36 weeks. If more than one blood pressure measure was available within the specified window, then the one closest to the scheduled visit was used for analysis. If no measure was available within this window, then the last recorded BP post-randomization was used for the endpoint. Analysis of covariance model was used with the factors: baseline blood pressure, treatment and blood pressure target group at randomization.
Outcome measures
| Measure |
Usual Care
n=504 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=339 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=649 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in Mean Sitting Systolic Blood Pressure
|
-10 mmHg
Interval -11.3 to -8.8
|
-11.6 mmHg
Interval -13.1 to -10.0
|
-14.4 mmHg
Interval -15.5 to -13.2
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Last Observation Carried Forward (LOCF) imputation technique is used for this analysis.
The visit window was from 22 to 36 weeks. If more than one blood pressure measure was available within the specified window, then the one closest to the scheduled visit was used for analysis. If no measure was available within this window, then the last recorded BP post-randomization was used for the endpoint. Analysis of covariance model was used with the factors: baseline blood pressure, treatment and blood pressure target group at randomization.
Outcome measures
| Measure |
Usual Care
n=504 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=339 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=649 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in Mean Sitting Diastolic Blood Pressure
|
-5.45 mmHg
Interval -6.2 to -4.7
|
-6.9 mmHg
Interval -7.9 to -5.9
|
-8.29 mmHg
Interval -9.0 to -7.6
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Only patients with measurements at both baseline and week 26 were included in this analysis.
The absolute cardiovascular risk assessment uses the Framingham Risk Equation to predict risk of a cardiovascular event over the next 5 years. A score of \<10% is a low risk, 10 to 15% is a moderate risk, and \>15% is a high risk. A decrease indicates improvement.
Outcome measures
| Measure |
Usual Care
n=397 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=252 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=492 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in Absolute Cardiovascular Risk Score
|
-2.6 percentage risk score change
Standard Deviation 4.5
|
-3.3 percentage risk score change
Standard Deviation 4.6
|
-3.9 percentage risk score change
Standard Deviation 4.5
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Safety analysis - consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment.
The rate of all adverse events by preferred terms as determined by the General Practice investigators to be related to study intervention therapy was reported. Percentage of adverse events was calculated based on the number of participants analyzed. 41 adverse events were not reported as inadequate information was supplied to allow determination of drug treatment at onset.
Outcome measures
| Measure |
Usual Care
n=524 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Number of Patients With at Least One Adverse Events Attributable to Anti-hypertensive Therapy
|
70 participants
|
70 participants
|
169 participants
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization.
A comparison of the early responders was made based on the blood pressure measurements taken at the week 6 visit window according to gender and guideline targets. The guideline targets were: patients with renal impairment: 125/75 mmHg; patients with end-organ damage/cardiovascular disease: 130/80 mmHg; others: 140/90 mmHg.
Outcome measures
| Measure |
Usual Care
n=524 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Female patients with a target of <140/90 mmHg
|
18 Participants
|
11 Participants
|
42 Participants
|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Male patients with a target of <125/75 mmHg
|
3 Participants
|
3 Participants
|
6 Participants
|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Male patients with a target of <130/80 mmHg
|
27 Participants
|
14 Participants
|
34 Participants
|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Male patients with a target of <140/90 mmHg
|
31 Participants
|
22 Participants
|
48 Participants
|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Female patients with a target of <125/75 mmHg
|
2 Participants
|
2 Participants
|
2 Participants
|
|
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments
Female patients with a target of <130/80 mmHg
|
16 Participants
|
5 Participants
|
34 Participants
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Only patients with measurements at both baseline and week 26 were included in this analysis.
The EQ-5D total indexed score (AUS) measures self-reported quality of life with the following 5 dimensions: mobility (range 1,2,3), self-care (range 1,2,3), usual activity (range 1,2,3), pain/discomfort (range 1,2,3) and anxiety/depression (range 1,2,3), where a 1 indicates no problems, a 2 indicates moderate problems, and a 3 indicates severe problems. The range of possible utility scores are between -0.217 (derived from worse responses from all 5 dimensions with severe problems ie 3,3,3,3,3) and 1.000 (no problems for all 5 dimensions) for each dimension. An increase in EQ-5D indexed score (AUS) indicates improvement.
Outcome measures
| Measure |
Usual Care
n=406 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=264 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=511 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in the EQ-5D Score
|
-0.007 change in EQ-5D score
Interval -0.022 to 0.008
|
0.017 change in EQ-5D score
Interval -0.001 to 0.036
|
0.011 change in EQ-5D score
Interval -0.003 to 0.024
|
SECONDARY outcome
Timeframe: Baseline and week 26Population: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Only patients with measurements at both baseline and week 26 were included in this analysis.
Patients with depression refers to potential depressive symptoms, not clinically diagnosed depression. The 2 question Arrol screening tool was used to determine if the patient had potential depressive symptoms. The 2 questions are: During the last month have you often been bothered by feeling down, depressed or hopeless? During the past month have you often been bothered by little interest or pleasure in doing things? The presence of potential depressive symptoms was determined by a 'yes' answer to either of these questions.
Outcome measures
| Measure |
Usual Care
n=458 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=285 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=547 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Number of Patients With Depression
Baseline
|
154 participants
|
96 participants
|
185 participants
|
|
Number of Patients With Depression
Week 26
|
129 participants
|
78 participants
|
151 participants
|
SECONDARY outcome
Timeframe: Baseline and week 26Population: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Only patients with measurements at both baseline and week 26 were included in this analysis.
The CES-D score was from 0 to 30, with a higher score indicating a higher level of depression. The categories for the score are: 0 to 9 suggests no depression; 10 to 15 suggests mild depression; 16 to 24 suggests moderate depression; 24 or above suggests severe depression.
Outcome measures
| Measure |
Usual Care
n=88 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=49 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=93 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline to Week 26
|
1.03 change in CES-D score
Standard Deviation 9.24
|
-1.12 change in CES-D score
Standard Deviation 10.95
|
1.19 change in CES-D score
Standard Deviation 11.09
|
SECONDARY outcome
Timeframe: Baseline and week 26Population: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization.
A patient was considered to have end organ damage with either of the following: 1) proteinuria (dipstick = 1+ or more or protein/creatinine ratio \> 30mg/mol or 24h urine protein \> 0.3g); 2) no proteinuria, but presence of microalbuminuria (urine albumin/creatinine ratio 3.6 to 25mg/mol(male) or 3.6 to 35mg/mol (female) detected; 3) no proteinuria or microalbuminuria, but presence of macroalbuminuria (urine albumin/creatinine ratio \> 25mg/mol(male) or \>35mg/mol (female) detected OR 4) ECG evidence of LVH (Sokolow-Lyon voltage criteria values \>= 38mm). Baseline potential for end organ damage was calculated in all 1562 randomised patients based on the criteria outlined above. If no investigation/data available, assumed no end-organ damage. It is important to note that given the limited number of ECGs at 26 weeks, between group comparisons should be limited to the two time points (baseline and 26 weeks).
Outcome measures
| Measure |
Usual Care
n=524 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Participants With End Organ Disease at Baseline and Week 26
Baseline
|
226 participants
|
146 participants
|
315 participants
|
|
Participants With End Organ Disease at Baseline and Week 26
Week 26 (N = 433, 277, 536)
|
157 participants
|
88 participants
|
177 participants
|
SECONDARY outcome
Timeframe: Baseline and week 26Population: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization. Only patients with measurements at both baseline and week 26 were included in this analysis.
A modified self-care behavior tool (questionnaire) was used to calculate 2 domain scales: maintenance and confidence. Each domain has a standardized score between 0 and 100. Self-care is best represented by maintenance. Confidence is an important process that moderates the relationship between self-care and outcomes. Higher index score suggests better self-care. A score of 70 or greater can be used as the cut-point to judge self-care adequacy.
Outcome measures
| Measure |
Usual Care
n=426 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=273 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=523 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Change in Self-care Behavior Score From Baseline to Week 26
Maintenance score
|
2.59 Change in score
Standard Deviation 13.56
|
2.27 Change in score
Standard Deviation 12.56
|
3.17 Change in score
Standard Deviation 12.38
|
|
Change in Self-care Behavior Score From Baseline to Week 26
Confidence score (N = 422, 269, 520)
|
0.93 Change in score
Standard Deviation 21.04
|
-0.72 Change in score
Standard Deviation 20.04
|
-0.71 Change in score
Standard Deviation 20.16
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: This data will not be analyzed due to the poor quality of the data.
The rate of compliance was planned to be estimated from the quantity of unused medication returned at each scheduled visit over the entire follow-up period. Rate of compliance = (tablets supplied - tablets returned)/(tablets for 100% compliance).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksPopulation: Intent-to-treat (ITT) - ITT population consisted of all subjects randomized to a study intervention arm and who commenced study management and/or treatment and who had at least one recorded BP post randomization.
Major clinical endpoints measured were all-cause mortality and fatal and non-fatal cardiovascular events (e.g. acute myocardial infarction, stroke and heart failure).
Outcome measures
| Measure |
Usual Care
n=524 Participants
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 Participants
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 Participants
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|
|
Number of Patients With Major Clinical Endpoints
All-cause mortality
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Patients With Major Clinical Endpoints
Non-fatal cardiovascular events
|
15 participants
|
6 participants
|
13 participants
|
Adverse Events
Pre-randomization
Serious events: 27 serious events
Other events: 95 other events
Deaths: 0 deaths
Usual Care
Serious events: 24 serious events
Other events: 47 other events
Deaths: 0 deaths
Monotherapy (Initial Monotherapy Arm)
Serious events: 15 serious events
Other events: 36 other events
Deaths: 0 deaths
Combination (Initial Combination Therapy Arm)
Serious events: 22 serious events
Other events: 105 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pre-randomization
n=2185 participants at risk
Pre-randomization
|
Usual Care
n=524 participants at risk
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 participants at risk
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 participants at risk
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Acute myocardial infarction
|
0.05%
1/2185
|
0.19%
1/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Cardiac disorders
Angina pectoris
|
0.05%
1/2185
|
0.57%
3/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/2185
|
0.19%
1/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Cardiac disorders
Chest discomfort
|
0.00%
0/2185
|
0.38%
2/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Chest pain
|
0.09%
2/2185
|
0.19%
1/524
|
0.28%
1/360
|
0.74%
5/678
|
|
Cardiac disorders
Coronary artery disease
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Dizziness
|
0.05%
1/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Cardiac disorders
Dyspnoea
|
0.00%
0/2185
|
0.57%
3/524
|
0.28%
1/360
|
0.59%
4/678
|
|
Cardiac disorders
Myocardial infarction
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Pulmonary oedema
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Cardiac disorders
Syncope
|
0.05%
1/2185
|
0.38%
2/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Endocrine disorders
Hyperparathyroidism
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Enlarged uvula
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Melaena
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Nausea
|
0.05%
1/2185
|
0.19%
1/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Rectal polyp
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Gastrointestinal disorders
Vomiting
|
0.05%
1/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.15%
1/678
|
|
General disorders
Oedema peripheral
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.29%
2/678
|
|
General disorders
Pseudocyst
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
General disorders
Pyrexia
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Infections and infestations
Appendicitis
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Infections and infestations
Arthritis infective
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Infections and infestations
Cellulitis
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Infections and infestations
Infection
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Infections and infestations
Otitis media
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Infections and infestations
Pneumonia
|
0.05%
1/2185
|
0.19%
1/524
|
0.28%
1/360
|
0.15%
1/678
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Injury, poisoning and procedural complications
Fall
|
0.09%
2/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Investigations
Biopsy prostate
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Investigations
Blood test abnormal
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Investigations
Liver function test abnormal
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Investigations
Vitamin B12 increased
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Musculoskeletal and connective tissue disorders
Neck mass
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cystosarcoma phyllodes
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.15%
1/678
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage unspecified
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Nervous system disorders
Exertional headache
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Nervous system disorders
Transient ischaemic attack
|
0.09%
2/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Psychiatric disorders
Anxiety
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Psychiatric disorders
Bipolar disorder
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
|
Psychiatric disorders
Delusion
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Psychiatric disorders
Drug abuse
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Psychiatric disorders
Intentional drug misuse
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Psychiatric disorders
Post-traumatic stress disorder
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Reproductive system and breast disorders
Breast mass
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/2185
|
0.00%
0/524
|
0.56%
2/360
|
0.00%
0/678
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/2185
|
0.38%
2/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Surgical and medical procedures
Arthroscopic surgery
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Surgical and medical procedures
Bladder neoplasm surgery
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Surgical and medical procedures
Nephrectomy
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Surgical and medical procedures
Umbilical hernia repair
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.15%
1/678
|
|
Vascular disorders
Hypertension
|
0.05%
1/2185
|
0.00%
0/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/2185
|
0.19%
1/524
|
0.00%
0/360
|
0.00%
0/678
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/2185
|
0.00%
0/524
|
0.28%
1/360
|
0.00%
0/678
|
Other adverse events
| Measure |
Pre-randomization
n=2185 participants at risk
Pre-randomization
|
Usual Care
n=524 participants at risk
Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target
|
Monotherapy (Initial Monotherapy Arm)
n=360 participants at risk
Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
Combination (Initial Combination Therapy Arm)
n=678 participants at risk
Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.
|
|---|---|---|---|---|
|
Cardiac disorders
Dizziness
|
3.5%
77/2185
|
4.4%
23/524
|
7.8%
28/360
|
6.2%
42/678
|
|
General disorders
Oedema peripheral
|
0.92%
20/2185
|
5.2%
27/524
|
2.5%
9/360
|
9.9%
67/678
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER