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Cardiovascular DiseasePhase 4NCT02740699

CT COMPARE: CT Coronary Angiography to Measure Plaque Reduction

A Phase 4 study testing Rosuvastatin, Atorvastatin and Cardiac Computed Tomography (CT) in people with Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Background: Coronary artery disease causes plaque in arteries. This can cause stroke or heart disease. Drugs called statins might shrink plaque. Researchers want to study how CT scanning can determine if an individuals arterial plaque has decreased while taking statins. Read more about this study

Who is it for?
Ages 40 to 75 years
Conditions the study is for
Cardiovascular Disease
What is being tested?
Rosuvastatin, Atorvastatin and Cardiac Computed Tomography (CT)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
1 siteUnited States
Study dates
11 Apr 2016to 11 Mar 2022
Phase
Phase 4
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 40 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men greater than or equal to 40 and less than or equal to 75 years of age; women greater than or equal to 40 and less than or equal to 75 years of age
  • Willing to travel to the NIH for follow-up visits.
  • Willing to start or modify statin therapy.
  • Able to understand and sign informed consent.
  • Eligible for primary prevention statin therapy
  • Eligible for at least moderate intensity statin according to 2013 ACC/AHA GRCR (i.e., greater than or equal to 5% 10 year cardiovascular risk, https://my.americanheart.org/professional/StatementsGuidelines/Prevention-Guidelines_UCM_457698_SubHomePage.jsp) OR
  • low (<5%) 10 year cardiovascular risk per 2013 ACC/ AHA and with coronary artery calcium score greater than or equal to 300 Agatston units or greater than or equal to 75 percentile for age, sex, and ethnicity determined per MESA study
  • (http://www.mesa-nhlbi.org/calcium/input.aspx).

Who cannot join

  • Allergy or prior clinically relevant adverse reaction to Rosuvastatin (does not include minor muscle pain).
  • High intensity statin treatment for more than 90 days prior to enrollment
  • LDL greater than or equal to 190 mg/ml
  • Physician-diagnosed heart attack
  • Physician-diagnosed stroke or TIA
  • Physician-diagnosed heart failure
Show all 17Show fewer
  • Having undergone procedures related to cardiovascular disease (CABG, angioplasty, valve replacement, pacemaker or defibrillator implantation, any surgery on the heart or arteries)
  • Active treatment for cancer
  • Prior hypersensitivity reaction to iodinated contrast injection
  • Known hyperthyroidism.
  • Acute renal failure, renal transplant, dialysis and renal failure clinically diagnosed.
  • History of liver transplant or severe liver disease or unexplained elevation of baseline ALT>3x upper limit of normal
  • Pregnancy and nursing
  • Mental, neurologic or social condition preventing understanding of the rationale, procedures, risks and potential benefits associated with the trial.
  • Any other conditions that precludes safety for MRI and/or CT imaging per the researcher's evaluation.
  • Individuals with hemoglobinopathies or severe asthma.
  • Severe renal excretory dysfunction, estimated glomerular filtration (eGFR) rate < 30 mL/min/1.73m2 body surface area according to the Modification of Diet in Renal Disease criteria Glomerular filtration rate will be estimated using the MDRD 2005 revised study formula: eGFR (mL/min/1.73m2) = 175 x (standardized serum creatinine)-1.154 x (age)-0.203 x 0.742 (if the subject is female) or x 1.212 (if the subject is black)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

Coronary artery disease causes plaque in arteries. This can cause stroke or heart disease. Drugs called statins might shrink plaque. Researchers want to study how CT scanning can determine if an individuals arterial plaque has decreased while taking statins.

Read more

Objectives:

To measure the change in coronary artery plaque volume in people treated with high-intensity statin therapy using CT and MRI scans. To study the metabolic activity of plaque in arteries. To determine how well plaque measurements from heart CT scans can be replicated.

Eligibility:

Men ages 40-75 and women ages 40-75 who are good candidates for statin treatment

Design:

Visit 1: participants will be screened with:

  • Medical history
  • Blood tests
  • Heart MRI and CT scan: An IV inserted into an arm or hand vein removes blood and injects contrast, and medicine if needed. Participants lie on a table that slides into a machine that takes pictures of the body. For the CT scan, if their heart rate is too high, they get medicine to lower it. They breathe in a special way, holding their breath for 5 seconds.

Participants will begin high-intensity statin treatment.

Participants will have 7 more visits over 3 years. All visits include blood tests and medication review. Some may also include:

  • Statin treatment adjustment
  • CT scan
  • MRI scan
  • Physical exam

Participants may join the PET Substudy. This includes 5 more visits during the study. These include:

  • Getting an IV in an arm vein
  • Blood tests
  • PET scans: They fast 12 hours before.

Participants may join the Reproducibility Substudy if they had a slow heart rate during their first CT scan. This includes 1 additional heart CT scan 4 weeks later.

Read the detailed description

In high risk patients undergoing invasive angiography, intravascular ultrasound (IVUS) has shown reduction of plaque for patients treated with HMG-CoA reductase inhibitors (statins). However, there is no accepted noninvasive method to determine if treatment for atherosclerosis results in reduction of coronary artery plaque.

Coronary artery CT angiography (CCTA) is noninvasive and can accurately determine the degree of coronary artery stenosis. In addition, the extent of calcified and noncalcified plaque may be directly measured using this technology at low radiation dose using state-of-the-art CT scanners. Several retrospective studies have previously suggested that CCTA may be able to show plaque regression in the coronary arteries due to statin therapy.

The primary aim of this proposal is to determine the change in coronary artery plaque volume in individuals treated with high intensity statin therapy as defined by 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.

Men and women who meet the inclusion and exclusion criteria will undergo CCTA examination for the presence or absence of coronary artery plaque. Individuals with evidence of noncalcified coronary plaque by CCTA and who meet criteria for HMG-CoA reductase (statin) therapy will be evaluated for a total of 36 months. The change of coronary artery plaque (progression or no change, or regression) in individuals with noncalcified plaque at baseline will be measured by CCTA at yearly intervals.

Being tested
Rosuvastatin, Atorvastatin, Cardiac Computed Tomography (CT), Cardiac Magnetic Resonance Image (MRI)
Keywords
Cholesterol, Heart Disease, CT Scan, Crestor, Lipitor
Medical subject headings
Cardiovascular Diseases, Heart Diseases

What participants receive

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

  • RosuvastatinDrug

    Also called Crestor

    Participants will receive 20-40 mg once daily

  • AtorvastatinDrug

    Also called Lipitor

    Participants will receive 40-80 mg once daily.

  • Cardiac Computed Tomography (CT)Radiation

    Also called Cardiac CT angiography (CCTA)

    Cardiac CT angiography (CCTA) provides a non-invasive method of evaluating both calcified and noncalcified plaque volume. Performed at baseline, 12 months 24 months, and 36 months.

  • Cardiac Magnetic Resonance Image (MRI)Radiation

    Also called Cardiovascular Magnetic Resonance Imaging (CMR)

    Provides a non-invasive method of evaluating both calcified and noncalcified plaque volume. Cardiac MRI may be performed at baseline, and 24 months (optional).

Study groups in NCT02740699
Study groupRoleWhat they receive
Moderate to High Statin Treatment in Participants with Coronary Artery PlaqueOtherParticipants with coronary artery plaque will receive moderate to high statin treatment at either 20-40 mg once daily Rosuvastatin or 40-80 mg once daily of Atorvastatin.
Receives: Drug: Rosuvastatin; Drug: Atorvastatin; Radiation: Cardiac Computed Tomography (CT); Radiation: Cardiac Magnetic Resonance Image (MRI)

What is being measured

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

  1. Mean Change of Non-calcified Plaque Volume in Participants Treated With High Intensity Statin Therapy Assessed by Coronary Computed Tomography Angiography

    Mean change of non-calcified plaque volume assessed by Coronary computed tomography angiography in participants treated with high intensity statin therapy (as defined by the 2013 ACC/AHA Guidelines to Reduce Cardiovascular Risk (GRCR).

    Using anatomical landmarks, a target plaque volume will be defined at baseline and follow up examinations. Software will be used to trace lumen and outer vessel boundaries to determine non-calcified plaque volume.

    The 2013 ACC/AHA Guidelines to GRCR focuses on the assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk and management of elevated blood cholesterol and body weight in adults. High-intensity statin therapy is defined by: rosuvastatin 20-40 mg or atorvastatin 40-80 mg. The maximum statin dose will be administered that is tolerated by the patient and that maintains LDL-C > or = 25 mg/dl. High-intensity statin therapy is defined as lowering LDL-C on average by approximately > or = 50%.

    Measured: Baseline and 24 months

Secondary outcomes (5)

  1. Mean Change of Non-calcified Plaque Volume in Participants Treated With High Intensity Statin Therapy Assessed by Coronary Computed Tomography Angiography

    Mean change of non-calcified plaque volume assessed by Coronary computed tomography angiography in participants treated with high intensity statin therapy (as defined by the 2013 ACC/AHA Guidelines to Reduce Cardiovascular Risk (GRCR).

    Using anatomical landmarks, a target plaque volume will be defined at baseline and follow up examinations. Software will be used to trace lumen and outer vessel boundaries to determine non-calcified plaque volume.

    The 2013 ACC/AHA Guidelines to GRCR focuses on the assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk and management of elevated blood cholesterol and body weight in adults. High-intensity statin therapy is defined by: rosuvastatin 20-40 mg or atorvastatin 40-80 mg. The maximum statin dose will be administered that is tolerated by the patient and that maintains LDL-C > or = 25 mg/dl. High-intensity statin therapy is defined as lowering LDL-C on average by approximately > or = 50%.

    Measured: Baseline and 36 months

  2. Linear Mixed-effects Regression Coefficient of Age Effect on Plaque Volume

    Linear mixed-effects regression coefficient of age effect on plaque volume measured by Coronary artery CT angiography. Plaque volumes (mm3) were quantified from coronary CTA exams using a validated automated method developed by Cleerly. Regression coefficient is the mean change of plaque volume given one year increase of age. In the mixed-effects model the outcomes are plaque volumes measured at Baseline, 24 months and 36 months as described in 2011 "Applied Longitudinal Analysis" Wiley Series in Probability and Statistics by Fitzmaurice, Laird, and Ware.

    Measured: Baseline, 24 months and 36 months

  3. Linear Mixed-Effects Regression Coefficient of Sex Effect on Plaque Volume (Beta Coefficient)

    Linear Mixed-effects Regression Coefficient of sex (female = 0 and male = 1) effect on plaque volume measured by Coronary artery CT angiography (beta coefficient). Plaque volumes (mm3) were quantified from coronary CTA exams using a validated automated method developed by Cleerly. Regression coefficient is the mean change of plaque volume comparing male verses female (female =0 and male = 1). In the mixed-effects model the outcomes are plaque volumes measured at Baseline, 24 months and 36 months as described in 2011 "Applied Longitudinal Analysis" Wiley Series in Probability and Statistics by Fitzmaurice, Laird, and Ware.

    Measured: Baseline, 24 months and 36 months

  4. Linear Mixed-effects Regression Coefficient of Race Effect on Plaque Volume (Beta Coefficient)

    Linear Mixed-effects Regression Coefficient of Effects race (white = 1 and non-white = 0) effect on plaque volume measured by Coronary artery CT angiography. Plaque volumes (mm3) were quantified from coronary CTA exams using a validated automated method developed by Cleerly. Regression coefficient is the mean change of plaque volume comparing race (white = 1 and non-white = 0). In the mixed-effects model the outcomes are plaque volumes measured at Baseline, 24 months and 36 months as described in 2011 "Applied Longitudinal Analysis" Wiley Series in Probability and Statistics by Fitzmaurice, Laird, and Ware.

    Measured: Baseline, 24 months and 36 months

  5. Linear Mixed-effects Regression Coefficient of Body Mass Index Effect on Plaque Volume

    Linear Mixed-effects Regression Coefficient of Body Mass Index Effect on Plaque Volume measured by Coronary artery CT angiography. Plaque volumes (mm3) were quantified from coronary CTA exams using a validated automated method developed by Cleerly. Regression coefficient is the mean change of plaque volume given one kg/m^2 increase of BMI. In the mixed-effects model the outcomes are plaque volumes measured at Baseline, 24 months and 36 months as described in 2011 "Applied Longitudinal Analysis" Wiley Series in Probability and Statistics by Fitzmaurice, Laird, and Ware.

    Measured: Baseline, 24 months and 36 months

Timeline

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

  1. First posted15 Apr 2016 (estimated)
  2. Study start11 Apr 2016
  3. Primary completion27 Jan 2022
  4. Study completion11 Mar 2022

Why it stopped: Principal Investigator resigned and closed program

Resources

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02740699
Sponsor's protocol ID
160089
Other IDs
16-H-0089
Status last verified
Mar 2022
First submitted
14 Apr 2016
Last updated
9 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • D'Ascenzo F, Agostoni P, Abbate A, Castagno D, Lipinski MJ, Vetrovec GW, Frati G, Presutti DG, Quadri G, Moretti C, Gaita F, Zoccai GB. Atherosclerotic coronary plaque regression and the risk of adverse cardiovascular events: a meta-regression of randomized clinical trials. Atherosclerosis. 2013 Jan;226(1):178-85. doi: 10.1016/j.atherosclerosis.2012.10.065. Epub 2012 Nov 6.

    PubMed 23206978

  • Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71. doi: 10.1016/S0140-6736(12)61190-8.

    PubMed 22883507

  • Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934. doi: 10.1016/j.jacc.2013.11.002. Epub 2013 Nov 12. No abstract available.

    PubMed 24239923

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Rosuvastatin, Atorvastatin and Cardiac Computed Tomography (CT) in people with Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

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 8 inclusion and 17 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: stopped early, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 9 Oct 2024). 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?

Mean Change of Non-calcified Plaque Volume in Participants Treated With High Intensity Statin Therapy Assessed by Coronary Computed Tomography Angiography (time frame: Baseline and 24 months). 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 NCT02740699, which also lists 3 linked publications.

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 9 Oct 2024.

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