CT COMPARE: CT Coronary Angiography to Measure Plaque Reduction

Cardiovascular Disease Clinical Trial

Official title:

CT COMPARE: CT Coronary Angiography to Measure Plaque Reduction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02740699
• Other study ID #: 160089
• Secondary ID: 16-H-0089
• Status: Terminated
• Phase: Phase 4
• Start date: April 11, 2016
• Est. completion date: March 11, 2022

Study information

• Verified date: March 2022
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. completion date: March 11, 2022
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

• INCLUSION CRITERIA:

A. 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

B. Willing to travel to the NIH for follow-up visits.

C. Willing to start or modify statin therapy.

D. Able to understand and sign informed consent.

E. Eligible for primary prevention statin therapy

1. 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_U CM_457698_SubHomePage.jsp) OR

2. 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).

EXCLUSION CRITERIA:

A. Allergy or prior clinically relevant adverse reaction to Rosuvastatin (does not include minor muscle pain).

B. High intensity statin treatment for more than 90 days prior to enrollment

C. LDL greater than or equal to 190 mg/ml

D. Physician-diagnosed heart attack

E. Physician-diagnosed stroke or TIA

F. Physician-diagnosed heart failure

G. Having undergone procedures related to cardiovascular disease (CABG, angioplasty, valve replacement, pacemaker or defibrillator implantation, any surgery on the heart or arteries)

H. Active treatment for cancer

I. Prior hypersensitivity reaction to iodinated contrast injection

J. Known hyperthyroidism.

K. Acute renal failure, renal transplant, dialysis and renal failure clinically diagnosed.

L. History of liver transplant or severe liver disease or unexplained elevation of baseline ALT>3x upper limit of normal

M. Pregnancy and nursing

N. Mental, neurologic or social condition preventing understanding of the rationale, procedures, risks and potential benefits associated with the trial.

O. Any other conditions that precludes safety for MRI and/or CT imaging per the researcher's evaluation.

P. Individuals with hemoglobinopathies or severe asthma.

Q. 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)

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Rosuvastatin
Participants will receive 20-40 mg once daily
• Atorvastatin
Participants will receive 40-80 mg once daily.

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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. Erratum In: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. J Am Coll Cardiol. 2015 Dec 22;66(24):2812. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To prospectively compare the change in coronary artery plaque burden determined by CCTA in asymptomatic individuals with moderate CVD risk treated either a) according to 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Athe...	compare the change in coronary artery plaque burden determined by CCTA in asymptomatic individuals with moderate CVD risk treated either a) according to 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults versus b) high intensity statin therapy.	24 months
Secondary	long-term effects of the statin therapy	1)Change in noncalcified plaque volume assessed by CCTA at the end of 36 months; 2)Effects of covariates including age, sex, race, body mass index and baseline plaque volume on the change of plaque volume measured by CCTA at 24 and 36 months. 3) The relationship of CMR T1 high signal intensity plaque and change in T1 signal by CMR over time to CCTA plaque characteristics.	36 months

External Links

•   NIH Clinical Center Detailed Web Page