NCT00862251

Brief Summary

The purpose of this study is to determine the efficacy of switching to a combination tablet ezetimibe/simvastatin (10mg/20mg) versus rosuvastatin (10 mg) versus doubling the statin dose in those patients who have cardiovascular disease and diabetes mellitus not adequately controlled on simvastatin 20 mg or atorvastatin 10 mg.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
808

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Apr 2009

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 16, 2009

Completed
16 days until next milestone

Study Start

First participant enrolled

April 1, 2009

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2011

Completed
1 year until next milestone

Results Posted

Study results publicly available

March 16, 2012

Completed
Last Updated

May 16, 2024

Status Verified

February 1, 2022

Enrollment Period

1.9 years

First QC Date

March 12, 2009

Results QC Date

February 23, 2012

Last Update Submit

May 8, 2024

Conditions

Keywords

cardiovascular disorder

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin).

    Baseline and Week 6

Secondary Outcomes (17)

  • In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin

    Baseline and Week 6

  • In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin

    Baseline and Week 6

  • Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin

    Baseline and Week 6

  • Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)

    Week 6

  • In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)

    Week 6

  • +12 more secondary outcomes

Study Arms (3)

Ezetimibe/simvastatin

EXPERIMENTAL
Drug: ezetimibe (+) simvastatinDrug: atorvastatin 10 mg or simvastatin 20 mg

Doubling statin dose

ACTIVE COMPARATOR
Drug: simvastatin 40 mg or atorvastatin 20 mgDrug: atorvastatin 10 mg or simvastatin 20 mg

Rosuvastatin

ACTIVE COMPARATOR
Drug: RosuvastatinDrug: atorvastatin 10 mg or simvastatin 20 mg

Interventions

ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.

Also known as: Vytorin
Ezetimibe/simvastatin

simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.

Also known as: Lipitor, Zocor
Doubling statin dose

rosuvastatin 10 mg tablets, taken once daily for six weeks.

Also known as: Crestor
Rosuvastatin

All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.

Also known as: Lipitor, Zocor
Doubling statin doseEzetimibe/simvastatinRosuvastatin

Eligibility Criteria

Age18 Years - 79 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient has not taken common statins or ezetimibe within 6 weeks of study screening or patient is currently taking a daily dose of the following statins for 6 weeks prior to study screening: simvastatin, atorvastatin, pravastatin, fluvastatin, ezetimibe, lovastatin, or ezetimibe + fluvastatin
  • Patient is willing to go on a cholesterol and glucose lowering diet for the duration of the study
  • Patient is willing to remain abstinent or use birth control for the duration of the study
  • Patient has Diabetes Mellitus with cardiovascular disease

You may not qualify if:

  • Patient has sensitivity to certain common statin drugs
  • Patient is Asian and would not be able to start taking the higher doses of rosuvastatin necessary for the study design
  • Patient consumes more than 2 alcoholic drinks per day
  • Patient is pregnant or breast-feeding
  • Patient has been treated with other investigational drugs within 30 days of first visit
  • Patient is currently on prohibited doses of the following statin drugs: rosuvastatin, simvastatin, atorvastatin, and pravastatin
  • Patient has congestive heart failure
  • Patient has uncontrolled high blood pressure
  • Patient has kidney disease
  • Patient has uncontrolled endocrine or metabolic disease which are known to possibly increase blood lipoproteins
  • Patient has diabetes mellitus that is not well controlled
  • Patient is human immunodeficiency virus (HIV) positive
  • Patient is currently taking medications that inhibit Cytochrome P450 3A4 (CYP3A4)
  • Patient is currently taking therapies that would increase the risk of muscle weakness
  • Patient has been taking certain over- the-counter lipid-lowering agents within 6 weeks prior to visit 1
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (4)

  • Le NA, Tomassini JE, Tershakovec AM, Neff DR, Wilson PW. Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid-Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease. J Am Heart Assoc. 2015 Oct 20;4(10):e001675. doi: 10.1161/JAHA.114.001675.

  • Rosen JB, Jimenez JG, Pirags V, Vides H, Massaad R, Hanson ME, Brudi P, Triscari J. Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects. Lipids Health Dis. 2013 Jul 16;12:103. doi: 10.1186/1476-511X-12-103.

  • Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, McPeters G, Brudi P, Triscari J. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86. doi: 10.1177/1479164112465212. Epub 2013 Jan 3.

  • Jimenez JG, Rosen JB, Pirags V, Massaad R, Hanson ME, Brudi P, Triscari J. The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid-lowering treatment strategies in diabetic subjects with and without metabolic syndrome. Diabetes Obes Metab. 2013 Jun;15(6):513-22. doi: 10.1111/dom.12059. Epub 2013 Jan 25.

MeSH Terms

Conditions

Cardiovascular DiseasesDiabetes Mellitus

Interventions

Ezetimibe, Simvastatin Drug CombinationSimvastatinAtorvastatinRosuvastatin Calcium

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsEzetimibeAzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPolycyclic CompoundsDrug CombinationsPharmaceutical PreparationsPyrrolesAzolesHeptanoic AcidsFatty AcidsLipidsSulfonamidesAmidesFluorobenzenesHydrocarbons, FluorinatedHydrocarbons, HalogenatedSulfonesSulfur CompoundsPyrimidines

Results Point of Contact

Title
Senior Vice President,Global Clinical Development
Organization
Merck Sharp & Dohme Corp

Study Officials

  • Medical Monitor

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

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
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2009

First Posted

March 16, 2009

Study Start

April 1, 2009

Primary Completion

March 1, 2011

Study Completion

March 1, 2011

Last Updated

May 16, 2024

Results First Posted

March 16, 2012

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will not share