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

NCT00797862 | Completed Phase 3 Results

• 1 other identifier: CSPA100A2307
• Study Type: interventional
• Target: 1,254
• Locations: 10 countries
• Sites: 10

Brief 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.

Conditions

Hypertension

Keywords

Aliskiren; Amlodipine; Hypertension; SPA1000; Norvasc

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, 8 weeks, 16 weeks, and 24 weeks

• 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.

  Baseline to 24 weeks

Secondary Outcomes (4)

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

  Baseline to 32 weeks

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

  Baseline, 8 weeks, 16 weeks and 24 weeks

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

  Baseline to 24 weeks

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

  Baseline to week 8, 16, 24 and 32 endpoints

Study Arms (3)

Aliskiren + Amlodipine

EXPERIMENTAL

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

Aliskiren Start - Amlodipine Add-On

EXPERIMENTAL

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

Amlodipine Start- Aliskiren Add-On

EXPERIMENTAL

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

Amlodipine DRUG

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

Also known as: Norvasc

Aliskiren + Amlodipine; Aliskiren Start - Amlodipine Add-On; Amlodipine Start- Aliskiren Add-On

hydrochlorothiazide DRUG

Hydrochlorothiazide 12.5 mg capsules were taken orally once daily

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

Aliskiren + Amlodipine; Aliskiren Start - Amlodipine Add-On; Amlodipine Start- Aliskiren Add-On

Aliskiren DRUG

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

Also known as: SPA 100

Aliskiren + Amlodipine; Aliskiren Start - Amlodipine Add-On; Amlodipine Start- Aliskiren Add-On

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (10)

Investigative Site

Toronto, Canada

Location

Investigative Site

San José, Costa Rica

Location

Investigative Site

Paris, France

Location

Investigative Site

Bonn, Germany

Location

Investigative Site

Athens, Greece

Location

Investigative Site

Guatemala City, Guatemala

Location

Investigative Site

Cape Town, South Africa

Location

Investigative Site

Basel, Switzerland

Location

Investigative Site

London, United Kingdom

Location

Investigative Site

Caracas, Venezuela

Location

Related Publications (2)

• 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.

  PMID: 26489809 DERIVED

• 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.

  PMID: 21236483 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Hydrochlorothiazide; aliskiren

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862- 778- 8300

Study Officials

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 25, 2008
• Study Start: November 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: October 17, 2011
• Results First Posted: May 17, 2011

Record last verified: 2011-06

Locations

VE (1); ZA (1); CA (1); DE (1); GU (1); GR (1); CH (1); FR (1); GB (1); CO (1)