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CompletedNCT00797862ACCELERATEUpdated Oct 17, 2011Results posted

Aliskiren and the Calcium Channel Blocker Amlodipine Combination as an Initial Treatment Strategy for Hypertension

A Phase 3 interventional study of Amlodipine and hydrochlorothiazide in Hypertension, sponsored by Novartis. Completed at 10 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2011-10-17.

Sponsored by Novartis · Phase 3, Interventional, and Diagnostic

Phase
Phase 3
Study type
Interventional
Enrollment
1,254
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study will compare the safety and efficacy of initial combination treatment with aliskiren + amlodipine to sequential add-on treatment strategies with aliskiren or amlodipine in patients with hypertension.

Read the detailed description

This study was designed to evaluate if patients with hypertension treated early with a combination therapy would achieve better blood pressure (BP) control, than patients being treated with a classical sequential add-on therapy.

The study compared the effects of the two treatment strategies: Treatment initiation on a single compound, either with aliskiren or amlodipine, and then continuation with the combination of both versus treatment initiation with the combination of aliskiren/amlodipine and then continuation with the combination. The study also evaluated if the overall mean sitting systolic blood pressure (msSBP)-lowering effect during the study, as well as the change from baseline to study end in msSBP, are superior in the group having received combination therapy from the beginning.

The study further evaluated the BP-lowering efficacy and tolerability of both treatment strategies.

02

Conditions studied

  • Hypertension

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Keywords

  • Aliskiren
  • Amlodipine
  • Hypertension
  • SPA1000
  • Norvasc
03

In context

Hypertension

6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.

This study's enrollment of 1,254 is above the median of 90 across 4,995 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

Novartis is the lead sponsor of 703 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female outpatients ≥ 18 years of age

  • Participants with essential hypertension:

    • Naive participants must have a mean sitting Systolic Blood Pressure (msSBP) ≥ 150 mmHg and \< 180 mmHg at Visit 1 and Visit 2. (Participants are considered 'naïve' if they have never been treated with any antihypertensive medication.)
    • All participants must have a msSBP ≥ 150 mmHg and \< 180 mmHg at Visit 2
  • Written informed consent to participate in this study prior to any study procedures

Exclusion criteria

Exclusion Criteria:

  • Severe hypertension
  • Pregnant or nursing (lactating) women
  • Pre-menopausal women not taking accepted form of birth control
  • Serum potassium ≥ 5.5 mEq/L (mmol/L) at Visit 1
  • History of cardiovascular conditions
  • Uncontrolled Type 1 or Type 2 diabetes mellitus
  • Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with similar chemical structures

Other protocol-defined inclusion/exclusion criteria may apply.

05

Study design

Phase
Phase 3
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
1,254 participants (actual)

Study arms

  • Experimental
    Aliskiren + Amlodipine

    Eligible participants received oral aliskiren 150 mg + amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of the combination treatment increased to aliskiren 300 mg + amlodipine 10 mg daily. From week 16-24, participants in this group continued combination treatment (aliskiren 300 mg + amlodipine 10 mg) for 8 weeks. At week 24, if blood pressure was not adequately controlled (systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.

    Drug: Amlodipine · Drug: hydrochlorothiazide · Drug: Aliskiren

  • Experimental
    Aliskiren Start - Amlodipine Add-On

    Eligible participants received oral aliskiren 150 mg daily from week 1-8. From week 8 - 16, the dose of aliskiren increased to 300 mg daily. From week 16-24, amlodipine 10 mg was added to the aliskiren 300 mg for 8 weeks (aliskiren 300 mg + amlodipine 10 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.

    Drug: Amlodipine · Drug: hydrochlorothiazide · Drug: Aliskiren

  • Experimental
    Amlodipine Start- Aliskiren Add-On

    Eligible participants received oral amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of amlodipine increased to 10 mg daily. From week 16-24, aliskiren 300 mg was added to the amlodipine 10 mg for 8 weeks (amlodipine 10 mg + aliskiren 300 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (amlodipine 10 mg + aliskiren 300 mg) for an additional 8 weeks. Total treatment period =32 weeks.

    Drug: Amlodipine · Drug: hydrochlorothiazide · Drug: Aliskiren

Interventions

  • DrugAmlodipine

    Amlodipine (5 mg and 10 mg) was provided as capsules taken orally once daily.

    Also known as: Norvasc

  • Drughydrochlorothiazide

    Hydrochlorothiazide 12.5 mg capsules were taken orally once daily

    Also known as: Esidrix, HydroDIURIL, Oretic, Ezide, Hydro-Par

  • DrugAliskiren

    Aliskiren 150 mg and aliskiren 300 mg were provided as film-coated tablets, taken orally once daily.

    Also known as: SPA 100

06

What researchers measure

Primary outcomes

  1. Overall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks

    Systolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msSBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures Analysis of Covariance (ANCOVA) model with treatment, visit, and region as factors, treatment by visit interaction and baseline msSBP as a covariate.

    Time frame: Baseline, 8 weeks, 16 weeks, and 24 weeks

  2. Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24

    Systolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region as factors, treatment by visit interaction and baseline msSBP as a covariate.

    Time frame: Baseline to 24 weeks

Secondary outcomes

  1. Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32

    Diastolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 32 weeks of study treatment. Change at Week 32 used a separate repeated measures ANCOVA model containing Week 8, 16, 24 and 32 data. Treatment, visit and region were factors in the model, treatment by visit interaction and baseline msDBP a covariate.

    Time frame: Baseline to 32 weeks

  2. Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks

    Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msDBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures ANCOVA model with treatment, visit and regions as factors, treatment by visit interaction and baseline msDBP as a covariate.

    Time frame: Baseline, 8 weeks, 16 weeks and 24 weeks

  3. Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24

    Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region, as factors, treatment by visit interaction and baseline msDBP as a covariate.

    Time frame: Baseline to 24 weeks

  4. Percentage of Participants Achieving Overall Blood Pressure Control at 8, 16, 24 and 32 Weeks Endpoints

    Systolic \& Diastolic Blood Pressure were measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and after 8, 16 , 24 and 32 weeks. Outcome is reported as percentage of participants achieving overall blood pressure control (msSBP \<140 mmHg and msDBP \<90 mmHg) at weeks 8, 16, 24 \& 32 endpoints.

    Time frame: Baseline to week 8, 16, 24 and 32 endpoints

07

Results

Posted May 17, 2011

Participant flow

Participant flow — Overall Study
MilestoneAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Started620318316
Entered double-blind treatment (fas)617315315
Completed496250230
Not completed1246886
Withdrew: Adverse event864458
Withdrew: Abnormal test procedure result011
Withdrew: Lack of efficacy176
Withdrew: No longer required study medication100
Withdrew: Withdrawal by subject1477
Withdrew: Lost to follow-up1105
Withdrew: Administrative problem400
Withdrew: Protocol violation468
Withdrew: Mis-randomized331

Outcome measures

PrimaryOverall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks

Systolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msSBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures Analysis of Covariance (ANCOVA) model with treatment, visit, and region as factors, treatment by visit interaction and baseline msSBP as a covariate.

Time frame:
Baseline, 8 weeks, 16 weeks, and 24 weeks
Reported as:
Least squares mean · mmHg
Overall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Overall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks-25.34 ± 0.436-17.94 ± 0.600-19.81 ± 0.611
PrimaryChange From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24

Systolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region as factors, treatment by visit interaction and baseline msSBP as a covariate.

Time frame:
Baseline to 24 weeks
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24-27.37 ± 0.546-26.34 ± 0.738-25.52 ± 0.782
SecondaryChange From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32

Diastolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 32 weeks of study treatment. Change at Week 32 used a separate repeated measures ANCOVA model containing Week 8, 16, 24 and 32 data. Treatment, visit and region were factors in the model, treatment by visit interaction and baseline msDBP a covariate.

Time frame:
Baseline to 32 weeks
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32-12.96 ± 0.323-12.96 ± 0.446-11.62 ± 0.467
SecondaryOverall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks

Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msDBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures ANCOVA model with treatment, visit and regions as factors, treatment by visit interaction and baseline msDBP as a covariate.

Time frame:
Baseline, 8 weeks, 16 weeks and 24 weeks
Reported as:
Least squares mean · mmHg
Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks-12.39 ± 0.247-8.37 ± 0.340-9.02 ± 0.347
SecondaryChange From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24

Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region, as factors, treatment by visit interaction and baseline msDBP as a covariate.

Time frame:
Baseline to 24 weeks
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24-13.64 ± 0.319-13.22 ± 0.431-12.25 ± 0.457
SecondaryPercentage of Participants Achieving Overall Blood Pressure Control at 8, 16, 24 and 32 Weeks Endpoints

Systolic \& Diastolic Blood Pressure were measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and after 8, 16 , 24 and 32 weeks. Outcome is reported as percentage of participants achieving overall blood pressure control (msSBP \<140 mmHg and msDBP \<90 mmHg) at weeks 8, 16, 24 \& 32 endpoints.

Time frame:
Baseline to week 8, 16, 24 and 32 endpoints
Reported as:
Number · Percentage of Participants
Percentage of Participants Achieving Overall Blood Pressure Control at 8, 16, 24 and 32 Weeks Endpoints
Percentage of ParticipantsAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Week 8 endpoint46.5 ± 0.56622.8 ± 0.78125.2 ± 0.816
Week 16 endpoint65.933.340.9
Week 24 endpoint63.462.857.8
Week 32 endpoint61.659.053.4
Post-hocChange From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 32

Systolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 32 weeks of study treatment. Change at week 32 used a separate repeated measures ANCOVA model containing Week 8, 16, 24 \& 32 data. Treatment, visit and region were factors in the model, treatment by visit interaction and baseline msSBP was a covariate.

Time frame:
Baseline to 32 weeks
Reported as:
Least squares mean · mmHg
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 32
mmHgAliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add On
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 32-26.42 ± 0.566-25.75 ± 0.781-24.32 ± 0.816

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Aliskiren + Amlodipine—14/617 (2.3%)196/617 (31.8%)
Aliskiren—9/315 (2.9%)81/315 (25.7%)
Amlodipine—9/315 (2.9%)104/315 (33%)
Most frequent serious events
Showing 10 of 38
Most frequent serious events
EventAliskiren + AmlodipineAliskirenAmlodipine
Angina pectorisCardiac disorders0/6170/3151/315
Atrial fibrillationCardiac disorders0/6171/3150/315
Cardiac failureCardiac disorders0/6170/3151/315
Hypertensive heart diseaseCardiac disorders0/6171/3150/315
Mitral valve incompetenceCardiac disorders0/6170/3151/315
Myocardial ischaemiaCardiac disorders0/6170/3151/315
Supraventricular tachycardiaCardiac disorders0/6171/3150/315
Gastrooesophageal reflux diseaseGastrointestinal disorders0/6170/3151/315
Intestinal obstructionGastrointestinal disorders0/6170/3151/315
Chest painGeneral disorders0/6171/3150/315
Most frequent other events
Most frequent other events
EventAliskiren + AmlodipineAliskirenAmlodipine
Oedema peripheralGeneral disorders131/61753/31576/315
Joint swellingMusculoskeletal and connective tissue disorders46/61720/31521/315
HeadacheNervous system disorders31/61720/31516/315

Baseline characteristics

Age Continuous
Age Continuous(years)Aliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add OnTotal
Mean58.1 ± 10.8158.4 ± 10.8358.1 ± 10.9358.1 ± 10.84
Sex: Female, Male
Sex: Female, Male(Participants)Aliskiren+AmlodipineAliskiren Start-Amlodipine Add OnAmlodipine Start-Aliskiren Add OnTotal
Female305154160619
Male315164156635
08

Study locations

10 sites
  • Investigative Site
    Toronto, Canada
  • Investigative Site
    San Jose, Costa Rica
  • Investigative Site
    Paris, France
  • Investigative Site
    Bonn, Germany
  • Investigative Site
    Athens, Greece
  • Investigative Site
    Guatemala city, Guatemala
  • Investigative Site
    Cape Town, South Africa
  • Investigative Site
    Basel, Switzerland
  • Investigative Site
    London, United Kingdom
  • Investigative Site
    Caracas, Venezuela
09

References and documents

Publications

  • Brown MJ, Williams B, Morant SV, Webb DJ, Caulfield MJ, Cruickshank JK, Ford I, McInnes G, Sever P, Salsbury J, Mackenzie IS, Padmanabhan S, MacDonald TM; British Hypertension Society's Prevention and Treatment of Hypertension with Algorithm-based Therapy (PATHWAY) Studies Group. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes Endocrinol. 2016 Feb;4(2):136-47. doi: 10.1016/S2213-8587(15)00377-0. Epub 2015 Oct 18. PubMed 26489809 ↗
  • Brown MJ, McInnes GT, Papst CC, Zhang J, MacDonald TM. Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet. 2011 Jan 22;377(9762):312-20. doi: 10.1016/S0140-6736(10)62003-X. Epub 2011 Jan 12. PubMed 21236483 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 17, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00797862
Lead sponsor
Novartis
First posted
Nov 25, 2008
Start date
Nov 2008
Primary completion
Nov 2010
Completion
Nov 2010
Results posted
May 17, 2011
Last update
Oct 17, 2011

Study contacts

Novartis
study chair · Novartis

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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