Carotid AtherosclerosisPhase 2MCATNCT00804843

Merck Carotid Atherosclerosis Trial (MK-0000-111)(COMPLETED)

A Phase 2 study testing Atorvastatin/niacin extended-release, Atorvastatin and Simvastatin in people with Carotid Atherosclerosis, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Carotid Atherosclerosis
What is being tested?: Atorvastatin/niacin extended-release, Atorvastatin and Simvastatin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100 participants
Where: No sites listed yet
Study dates: Apr 2009to Oct 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient is diagnosed with carotid stenosis AND is scheduled to undergo carotid endarterectomy
Female patients of reproductive potential must abstain from sex or use an acceptable method of birth control through out the study

Who cannot join

Patient must undergo CEA less than 4 weeks after entering study
Patient has recent history of acute coronary syndrome
Patient has has coronary artery bypass graft surgery within 30 days of study start
Patient has thyroid disease that has not been treated for more than 6 weeks
Patient has donated blood within 8 weeks of study start
Patient has poorly controlled diabetes mellitis

Show all 9Show fewer

Patient has human immunodeficiency virus (HIV) or Hepatitis B or C
Patient is taking warfarin or other anticoagulants
Patient is taking hormone replacement therapy

About this study

Official title: A Randomized Clinical Trial to Evaluate the Effects of High Dose Statin and Niacin Therapy on Excised Plaque Biomarkers in Patients Undergoing Carotid Endarterectomy (CEA)

This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers

Conditions: Carotid Atherosclerosis
Being tested: Atorvastatin/niacin extended-release, Atorvastatin, Simvastatin
Medical subject headings: Carotid Artery Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Atorvastatin/niacin extended-releaseDrug
Also called Lipitor, Niaspan
80 mg tablet atorvastatin once daily, 10 mg tablet placebo to atorvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.
AtorvastatinDrug
Also called Lipitor
10 mg tablet atorvastatin once daily, 80 mg tablet placebo to atorvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.
SimvastatinDrug
Also called Zocor
(Russia and Brazil) 80 mg tablet simvastatin once daily, 10 mg tablet placebo to simvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.
SimvastatinDrug
Also called Zocor
(Russia and Brazil) 10 mg tablet simvastatin once daily, 80 mg tablet placebo to simvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.

Study groups in NCT00804843
Study group	Role	What they receive
Statin 80 mg + Niacin extended-release (ER)	Experimental	Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin. Receives: Drug: Atorvastatin/niacin extended-release; Drug: Simvastatin
Statin 10 mg	Active comparator	Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. Receives: Drug: Atorvastatin; Drug: Simvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis
Excised carotid plaques were evaluated for the gene expression of 60 biomarkers associated with inflammation ("Hot" biomarkers) \& 25 biomarkers associated with stability ("Cold" biomarkers). Each biomarker was assayed using a quantitative polymerase chain reaction method and results were reported as a Cycle Threshold, (Ct). A Composite Score was calculated by averaging the Ct for each of the 25 "cold" genes, and subtracting the average Ct for the 60 "hot" genes. A higher composite score was associated with greater inflammation and a lower score was associated with stability (non-inflamed).
Measured: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
Plaque Instability Protein Composite Score
Each excised plaque was analyzed using an assay of 20 proteins that reflect plaque composition and inflammation. Each protein was assigned scaled signs, with a lower (negative) sign associated with plaque stability and a higher (positive) sign associated with plaque inflammation/instability. The Composite Score was the average amounts of all the 20 proteins with their associated signs. A higher Composite Score is associated with more plaque instability.
Measured: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay
Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.
Measured: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2009Oct 2010

First posted9 Dec 2008 (estimated)
Study startApr 2009
Primary completionOct 2010
Study completionOct 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Carotid AtherosclerosisStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00804843
Sponsor's protocol ID: 0000-111
Other IDs: 2008_598
Acronym: MCAT
Status last verified: Sep 2015
First submitted: 8 Dec 2008
Last updated: 30 Sep 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Carotid Atherosclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Clinical Trial to Evaluate the Effects of High Dose Statin and Niacin Therapy on Excised Plaque Biomarkers in Patients Undergoing Carotid Endarterectomy (CEA)
ClinicalTrials.gov ID: NCT00804843
Acronym / sponsor ID: MCAT / 0000-111
Conditions: Carotid Atherosclerosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Apr 2009
Primary completion: Oct 2010 (actual)
Study completion: Oct 2010 (actual)
First posted: 9 Dec 2008 (estimated)
Results: Posted 19 Apr 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Statin 80 mg + Niacin extended-release (ER)	Experimental	Drug: Atorvastatin/niacin extended-release, Drug: SimvastatinParticipants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin.
Statin 10 mg	Active comparator	Drug: Atorvastatin, Drug: SimvastatinParticipants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patient is diagnosed with carotid stenosis AND is scheduled to undergo carotid endarterectomy
Female patients of reproductive potential must abstain from sex or use an acceptable method of birth control through out the study

Key exclusion criteria (9 listed)

Patient must undergo CEA less than 4 weeks after entering study
Patient has recent history of acute coronary syndrome
Patient has has coronary artery bypass graft surgery within 30 days of study start
Patient has thyroid disease that has not been treated for more than 6 weeks
Patient has donated blood within 8 weeks of study start

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Atorvastatin/niacin extended-releaseAlso: Lipitor, Niaspan80 mg tablet atorvastatin once daily, 10 mg tablet placebo to atorvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.	Drug	Statin 80 mg + Niacin extended-release (ER)
AtorvastatinAlso: Lipitor10 mg tablet atorvastatin once daily, 80 mg tablet placebo to atorvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.	Drug	Statin 10 mg
SimvastatinAlso: Zocor(Russia and Brazil) 80 mg tablet simvastatin once daily, 10 mg tablet placebo to simvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.	Drug	Statin 80 mg + Niacin extended-release (ER)
SimvastatinAlso: Zocor(Russia and Brazil) 10 mg tablet simvastatin once daily, 80 mg tablet placebo to simvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.	Drug	Statin 10 mg

Primary outcome

Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis
Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
Excised carotid plaques were evaluated for the gene expression of 60 biomarkers associated with inflammation ("Hot" biomarkers) \& 25 biomarkers associated with stability ("Cold" biomarkers). Each biomarker was assayed using a quantitative polymerase chain reaction method and results were reported as a Cycle Threshold, (Ct). A Composite Score was calculated by averaging the Ct for each of the 25 "cold" genes, and subtracting the average Ct for the 60 "hot" genes. A higher composite score was associated with greater inflammation and a lower score was associated with stability (non-inflamed).
Plaque Instability Protein Composite Score
Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
Each excised plaque was analyzed using an assay of 20 proteins that reflect plaque composition and inflammation. Each protein was assigned scaled signs, with a lower (negative) sign associated with plaque stability and a higher (positive) sign associated with plaque inflammation/instability. The Composite Score was the average amounts of all the 20 proteins with their associated signs. A higher Composite Score is associated with more plaque instability.
Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay
Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.

Results and safety

Results posted to the registry on 19 Apr 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Statin 80 mg + Niacin Extended-release (ER)	50	40
Statin 10 mg	50	43

Primary outcome: Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis

Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing). Mean (Standard Deviation). Unit: Cycle threshold (Ct)

Measure	Statin 80 mg + Niacin Extended-release (ER) n = 36	Statin 10 mg n = 34
Value	1.36 (1.17)	0.82 (1.33)

Statin 80 mg + Niacin Extended-release (ER) vs Statin 10 mg: Least Square Mean Difference: 0.27 (90% CI -0.24 to 0.78), p = 0.811, ANOVA

Population analysed: Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the analysis.

Primary outcome: Plaque Instability Protein Composite Score

Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing). Mean (Standard Deviation). Unit: Score

Measure	Statin 80 mg + Niacin Extended-release (ER) n = 36	Statin 10 mg n = 34
Value	-7.19 (10.45)	-10.48 (11.70)

Statin 80 mg + Niacin Extended-release (ER) vs Statin 10 mg: Least Square Mean Difference: 3.64 (90% CI -1.09 to 8.36), p = 0.898, ANOVA

Population analysed: Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the analysis.

Primary outcome: Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay

Time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)

Population analysed: Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were to be included in the analysis. This was not performed due to technical concerns. Instead, the cholesterol content determination, if performed, will use mass spectrometry approach and would be an exploratory objective.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Statin 80 mg + Niacin Extended-release (ER)	9 of 50 (18%)	5 of 50 (10%)	Not reported
Statin 10 mg	7 of 50 (14%)	2 of 50 (4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atorvastatin/niacin extended-release, Atorvastatin and Simvastatin in people with Carotid Atherosclerosis, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis (time frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00804843.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2015.