AtherosclerosisPhase 4NCT01212900
Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression
A Phase 4 study testing Statins, HMG CoA in people with Atherosclerosis and Hypercholesterolemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Atherosclerosis (thickening of the artery walls caused by cholesterol and other deposits) commonly occurs in the heart vessels and carotid (neck) arteries of adults. This is often present in individuals with high cholesterol levels in their blood. Read more about this study
- Who is it for?
- Ages 50 to 99 years
- Conditions the study is for
- Atherosclerosis, Hypercholesterolemia
- What is being tested?
- Statins, HMG CoA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2010to 22 Feb 2017
- 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 50 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and Women greater than or equal to 55 years of age
- Candidates for lipid lowering therapy under NCEP ATP III guidelines without contraindication to statin therapy
- Willing to modify therapy to enroll in the study
- Willing to travel to the NIH for follow-up visits.
- Able to understand and sign informed consent
- Lab Eligibility parameters:
Show all 10Show fewer
- eGFR > 45 mL/min/m2
- For age >60 test GFR within 1 week prior to contrast; For age less than or equal to 60 test within 4 weeks
- Participants who are not participating in the CT Reproducibility study are eligible.
- Patients will be selected who had a one RR interval initial CT scan with less that 10.5 mSv estimated radiation dosage and who will not be participating in the PET Substudy.
Who cannot join
- Ineligibility for MR imaging due to:
- Previous pacemaker implantation
- Automatic implantable cardioverter-defibrillator (AICD)
- Metal implants or other ferromagnetic devices, or
- Foreign material
- Claustrophobia
Show all 23Show fewer
- Contra-indication or allergy to statin medications.
- Current statin therapy at or above the maximum dosage permitted per study protocol.
- Use of fibrates, ezetimibe, niacin, or bile acid binding agents within 6 months of screening visit.
- Pregnancy and nursing.
- Liver failure defined clinically and by laboratory data.
- 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.
- EXCLUSION FOR PARTICIPATION FOR GADOLINUIM CONTRAST. PARTICIPANTS MAY STILL UNDERGO ALL OTHER STUDY EVALUATIONS.
- (Inclusive of the above exclusion criteria):
- Allergy to gadolinium for scans using contrast; will be eligible for non-contrast scans.
- Acute renal failure, renal transplant, dialysis and renal failure (eGFR < 45 mL/min/m2 and/or clinically diagnosed).
- Individuals with a history of liver transplant or severe liver disease.<TAB>
- Individuals with hemoglobinopathies or severe asthma.
- EXCLUSION FOR PARTICIPATION FOR IODINATED CONTRAST. PARTICIPANTS MAY STILL UNDERGO ALL OTHER SUDY EVALUATIONS.
- Prior hypersensitivity reaction to iodinated contrast injection, renal dysfunction (defined as eGFR < 45 mL/min/ m2) or a current clinical diagnosis of renal failure.
- Patients who are unable or unwilling to comply with the physical activity restrictions or fast for 12 hours prior to FDG PET scanning will be excluded. Due to the need for dietary manipulation and the maintenance of strict glycemic control we will exclude diabetic patients from our initial study sample. Blood glucose measurements before injection must be within normal limits, less than 200 mg/dL (11 mmol/L).
- Patients who did not have a one RR interval initial CT scan. Patients who will participate in the PET Substudy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The RIGHT Study: Risk Stratification With Image Guidance of HMG Coa Reductase Inhibitor Therapy
Background:
- Atherosclerosis (thickening of the artery walls caused by cholesterol and other deposits) commonly occurs in the heart vessels and carotid (neck) arteries of adults. This is often present in individuals with high cholesterol levels in their blood. These patients are usually treated with cholesterol lowering medication ( statins ) along with modification of diet and exercise. Researchers are interested in investigating new approaches including magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies to detect blood vessel blockages that would not otherwise be detected by cholesterol levels and risk factors for heart disease.
Read more
Objectives:
- To measure atherosclerosis in the heart vessels and carotid arteries using imaging tests (computed tomography (CT) and magnetic resonance imaging (MRI)) before and after standard treatment with cholesterol lowering medication ( statins )
Eligibility:
- Healthy individuals at least 55 years of age who are candidates for therapy to lower their blood cholesterol levels.
Design:
- This study will involve one screening visit and seven study visits over a period of 2 years.
- Participants will be screened with a physical examination and medical history, as well as blood samples and tests to ensure that it is safe for them to have CT and MRI scans. Participants will provide information on current medications, dietary habits, smoking status, alcohol and caffeine intake, and their level of physical activity.
- Participants will be divided into two groups. One group will receive standard doses of medication to lower cholesterol according to current treatment guidelines, while the other group will have MRI scans of the carotid arteries and a CT scan of the heart to determine the best medication dose levels.
- Visits 3 to 5 will be scheduled 3, 6, and 9 months after visit 2. During these visits, researchers will monitor for possible side effects and may change or adjust medications and doses.
- At visit 6, participants will have an MRI scan of the carotid arteries, a physical examination, and blood tests. Medications may be changed or adjusted.
- At visit 7, participants will have blood tests, and medications may be changed or adjusted.
- At the final visit, participants will have MRI and CT scans of the carotid arteries and heart, respectively, as well as a final physical examination and blood tests.
Read the detailed description
The overall aim of this proposal is to compare the effectiveness of an image guided approach to lipid lowering to standard therapy guided by clinical risk factors and blood lipid levels. Men and women over age 55 who are candidates for statin therapy will be randomized to usual cholesterol lowering care, or to care guided by MRI images of the carotid arteries. Participants randomized to the second, imaging guided, group will be assigned to LDL cholesterol targets according to the degree of atherosclerosis seen by MRI. The study endpoints will be the total degree of plaque regression seen, the dosage of statin drugs required to achieve that reduction, and the rate of cardiovascular events.
FDG-PET is hypothesized to enable visualization of anti-inflammatory effects of statins that most likely occur before anatomic regression of the plaques can be demonstrated on MRI. A pilot substudy is to be conducted to explore this relationship. A subgroup of patients participating in the main study will be asked to participate in FDG PET imaging. The purpose of this pilot study is to determine if FDG avid lesions undergo a greater degree of morphologic regression with therapy controlling for the reduction in LDL cholesterol and the dosage of statins required to achieve that target.
Although contrast-enhanced coronary CT angiography (CTA) with multidetector computed tomography (MDCT) has been used extensively to characterize coronary artery plaque composition, there is little data regarding its reproducibility. A recent study demonstrated excellent reproducibility for this technique but this study was performed using the older 64 detector row CT scanners2. A pilot substudy will be conducted to study the reproducibility of coronary CT angiography using the newer generation of 320 detector row CT scanners.
- Conditions
- Atherosclerosis, Hypercholesterolemia
- Being tested
- Statins, HMG CoA
- Keywords
- Atherosclerosis, Cardiovascular Disease, Cardiac MRI, Cardiac CT, Cholesterol
- Medical subject headings
- Atherosclerosis, Hypercholesterolemia, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Statins, HMG CoADrug
Statin therapy
| Study group | Role | What they receive |
|---|---|---|
| Imaging | Experimental | Lipid targets assigned according to the severity of atherosclerotic plaque measured as wall volume in the common and internal carotid arteries by MRI Receives: Drug: Statins, HMG CoA |
| Standard | Active comparator | Standardized statin therapy based on NCEP ATP IIIR guidelines, including clinical risk factors and blood lipid levels. Receives: Drug: Statins, HMG CoA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean of Wall Volume of Internal Carotid Arteries
Wall volume of internal carotid arteries was measured using magnetic resonance imaging. Participants will undergo 2D and 3D carotid MRI using a 3 Tesla scanner and surface carotid coils. Participants with mild or no atherosclerosis, defined as the lowest tertile of wall volume, will have statin therapy adjusted to a target range of 100-130 mg/dL. Participants in the middle tertile will receive statin therapy adjusted to achieve a target LDL 70-100 mg/dL. Participants with the most severe atherosclerosis will receive statin therapy to an LDL target between 40 and 70 mg/dL. Participants in the Standard arm will have lipid sub-fraction targets determined according to estimated 10 year cardiovascular risk, as per standard NCEP guidelines.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2010 (estimated)
- Study start30 Sep 2010
- Primary completion30 Nov 2016
- Study completion22 Feb 2017
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nehal N Mehta, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01212900
- Sponsor's protocol ID
- 100214
- Other IDs
- 10-H-0214
- Status last verified
- 12 Feb 2018
- First submitted
- 30 Sep 2010
- Last updated
- 30 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zavodni AE, Wasserman BA, McClelland RL, Gomes AS, Folsom AR, Polak JF, Lima JA, Bluemke DA. Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA). Radiology. 2014 May;271(2):381-9. doi: 10.1148/radiol.14131020. Epub 2014 Mar 4.
PubMed 24592924Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AE, O'Leary DH. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2013 Apr 8;2(2):e000087. doi: 10.1161/JAHA.113.000087.
PubMed 23568342Sibley CT, Vavere AL, Gottlieb I, Cox C, Matheson M, Spooner A, Godoy G, Fernandes V, Wasserman BA, Bluemke DA, Lima JA. MRI-measured regression of carotid atherosclerosis induced by statins with and without niacin in a randomised controlled trial: the NIA plaque study. Heart. 2013 Nov;99(22):1675-80. doi: 10.1136/heartjnl-2013-303926. Epub 2013 Jul 19.
PubMed 23872591Sandfort V, Lai S, Ahlman MA, Mallek M, Liu S, Sibley CT, Turkbey EB, Lima JA, Bluemke DA. Obesity Is Associated With Progression of Atherosclerosis During Statin Treatment. J Am Heart Assoc. 2016 Jul 13;5(7):e003621. doi: 10.1161/JAHA.116.003621.
PubMed 27413040
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The RIGHT Study: Risk Stratification With Image Guidance of HMG Coa Reductase Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT01212900
- Acronym / sponsor ID
- 100214
- Conditions
- Atherosclerosis, Hypercholesterolemia
- Keywords
- Atherosclerosis, Cardiovascular Disease, Cardiac MRI, Cardiac CT, Cholesterol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 30 Sep 2010
- Primary completion
- 30 Nov 2016 (actual)
- Study completion
- 22 Feb 2017 (actual)
- First posted
- 1 Oct 2010 (estimated)
- Results
- Posted 31 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Atherosclerosis (thickening of the artery walls caused by cholesterol and other deposits) commonly occurs in the heart vessels and carotid (neck) arteries of adults. This is often present in individuals with high cholesterol levels in their blood. These patients are usually treated with cholesterol lowering medication ( statins ) along with modification of diet and exercise. Researchers are interested in investigating new approaches including magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies to detect blood vessel blockages that would not otherwise be detected by cholesterol levels and risk factors for heart disease.
Objectives:
- To measure atherosclerosis in the heart vessels and carotid arteries using imaging tests (computed tomography (CT) and magnetic resonance imaging (MRI)) before and after standard treatment with cholesterol lowering medication ( statins )
Eligibility:
- Healthy individuals at least 55 years of age who are candidates for therapy to lower their blood cholesterol levels.
Design:
- This study will involve one screening visit and seven study visits over a period of 2 years.
- Participants will be screened with a physical examination and medical history, as well as blood samples and tests to ensure that it is safe for them to have CT and MRI scans. Participants will provide information on current medications, dietary habits, smoking status, alcohol and caffeine intake, and their level of physical activity.
- Participants will be divided into two groups. One group will receive standard doses of medication to lower cholesterol according to current treatment guidelines, while the other group will have MRI scans of the carotid arteries and a CT scan of the heart to determine the best medication dose levels.
- Visits 3 to 5 will be scheduled 3, 6, and 9 months after visit 2. During these visits, researchers will monitor for possible side effects and may change or adjust medications and doses.
- At visit 6, participants will have an MRI scan of the carotid arteries, a physical examination, and blood tests. Medications may be changed or adjusted.
- At visit 7, participants will have blood tests, and medications may be changed or adjusted.
- At the final visit, participants will have MRI and CT scans of the carotid arteries and heart, respectively, as well as a final physical examination and blood tests.
Detailed description
The overall aim of this proposal is to compare the effectiveness of an image guided approach to lipid lowering to standard therapy guided by clinical risk factors and blood lipid levels. Men and women over age 55 who are candidates for statin therapy will be randomized to usual cholesterol lowering care, or to care guided by MRI images of the carotid arteries. Participants randomized to the second, imaging guided, group will be assigned to LDL cholesterol targets according to the degree of atherosclerosis seen by MRI. The study endpoints will be the total degree of plaque regression seen, the dosage of statin drugs required to achieve that reduction, and the rate of cardiovascular events.
FDG-PET is hypothesized to enable visualization of anti-inflammatory effects of statins that most likely occur before anatomic regression of the plaques can be demonstrated on MRI. A pilot substudy is to be conducted to explore this relationship. A subgroup of patients participating in the main study will be asked to participate in FDG PET imaging. The purpose of this pilot study is to determine if FDG avid lesions undergo a greater degree of morphologic regression with therapy controlling for the reduction in LDL cholesterol and the dosage of statins required to achieve that target.
Although contrast-enhanced coronary CT angiography (CTA) with multidetector computed tomography (MDCT) has been used extensively to characterize coronary artery plaque composition, there is little data regarding its reproducibility. A recent study demonstrated excellent reproducibility for this technique but this study was performed using the older 64 detector row CT scanners2. A pilot substudy will be conducted to study the reproducibility of coronary CT angiography using the newer generation of 320 detector row CT scanners.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imaging | Experimental | Drug: Statins, HMG CoALipid targets assigned according to the severity of atherosclerotic plaque measured as wall volume in the common and internal carotid arteries by MRI |
| Standard | Active comparator | Drug: Statins, HMG CoAStandardized statin therapy based on NCEP ATP IIIR guidelines, including clinical risk factors and blood lipid levels. |
Who may qualify
- Ages
- 50 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men and Women greater than or equal to 55 years of age
- Candidates for lipid lowering therapy under NCEP ATP III guidelines without contraindication to statin therapy
- Willing to modify therapy to enroll in the study
- Willing to travel to the NIH for follow-up visits.
- Able to understand and sign informed consent
Key exclusion criteria (23 listed)
- Ineligibility for MR imaging due to:
- Previous pacemaker implantation
- Automatic implantable cardioverter-defibrillator (AICD)
- Metal implants or other ferromagnetic devices, or
- Foreign material
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 |
|---|---|---|
| Statins, HMG CoAStatin therapy | Drug | Imaging, Standard |
Primary outcome
Change in Mean of Wall Volume of Internal Carotid Arteries
Time frame: 24 months
Wall volume of internal carotid arteries was measured using magnetic resonance imaging. Participants will undergo 2D and 3D carotid MRI using a 3 Tesla scanner and surface carotid coils. Participants with mild or no atherosclerosis, defined as the lowest tertile of wall volume, will have statin therapy adjusted to a target range of 100-130 mg/dL. Participants in the middle tertile will receive statin therapy adjusted to achieve a target LDL 70-100 mg/dL. Participants with the most severe atherosclerosis will receive statin therapy to an LDL target between 40 and 70 mg/dL. Participants in the Standard arm will have lipid sub-fraction targets determined according to estimated 10 year cardiovascular risk, as per standard NCEP guidelines.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24592924Zavodni AE, Wasserman BA, McClelland RL, Gomes AS, Folsom AR, Polak JF, Lima JA, Bluemke DA. Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA). Radiology. 2014 May;271(2):381-9. doi: 10.1148/radiol.14131020. Epub 2014 Mar 4.
- Background: PubMed 23568342Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AE, O'Leary DH. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2013 Apr 8;2(2):e000087. doi: 10.1161/JAHA.113.000087.
- Background: PubMed 23872591Sibley CT, Vavere AL, Gottlieb I, Cox C, Matheson M, Spooner A, Godoy G, Fernandes V, Wasserman BA, Bluemke DA, Lima JA. MRI-measured regression of carotid atherosclerosis induced by statins with and without niacin in a randomised controlled trial: the NIA plaque study. Heart. 2013 Nov;99(22):1675-80. doi: 10.1136/heartjnl-2013-303926. Epub 2013 Jul 19.
- Derived from this study: PubMed 27413040Sandfort V, Lai S, Ahlman MA, Mallek M, Liu S, Sibley CT, Turkbey EB, Lima JA, Bluemke DA. Obesity Is Associated With Progression of Atherosclerosis During Statin Treatment. J Am Heart Assoc. 2016 Jul 13;5(7):e003621. doi: 10.1161/JAHA.116.003621.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Atherosclerosis
Recruiting
Intracoronary Cryotherapy Effect on Stabilization of Vulnerable Plaque in Patients With Stable Angina or ACS - A Traditional Feasibility Study
Coronary Arterial Disease (CAD), Plaque
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Recruiting
Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension
Atherosclerosis Cardiovascular Disease
Active, not recruitingPhase 3
Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity
Atherosclerotic Cardiovascular Disease, Overweight
Active, not recruitingObservational study
A Retrospective Cohort Study Evaluating Major Adverse Cardiovascular Events and Cardiovascular Outcomes in Adults With Atherosclerotic Cardiovascular Disease Without Prior Ischemic Events (OPTIMUS RISK - Spain)
Atherosclerotic Cardiovascular Disease
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.
Nehal N Mehta, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Statins, HMG CoA in people with Atherosclerosis and Hypercholesterolemia, 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 10 inclusion and 23 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 Nov 2018. 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 31 Oct 2018). 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?
Change in Mean of Wall Volume of Internal Carotid Arteries (time frame: 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 NCT01212900, which also lists 4 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 30 Nov 2018.