Vascular InflammationPhase 3CIRTNCT02576067
Cardiovascular Inflammation Reduction Trial - Inflammation Imaging Study
A Phase 3 study testing Low dose methotrexate in people with Vascular Inflammation and Atherosclerotic Cardiovascular Disease, run by Icahn School of Medicine at Mount Sinai at 3 sites in 2 countries.
Trial summary
Vascular inflammation, a central feature of atherosclerosis, participates in the initiation, perpetuation and instability of plaques. Multiple clinical trials of cholesterol lowering therapy with statins have demonstrated that reductions in atherosclerotic cardiovascular disease (CVD) events are associated with… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vascular Inflammation, Atherosclerotic Cardiovascular Disease
- What is being tested?
- Low dose methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 18 Dec 2015to 29 Mar 2019
- Phase
- Phase 3
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years at screening
- Documented MI in the past or past evidence of multivessel coronary artery disease by angiography must have completed any planned coronary revascularization procedures associated with the qualifying event, and must be clinically stable for at least 60 d before screening; the qualifying prior MI must be documented either by hospital records or by evidence on current electrocardiogram of Q waves in 2 contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar; the qualifying documentation of multivessel coronary disease must include angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis.
- History of type 2 diabetes or metabolic syndrome at the time of study enrollment
- Willing to participate as evidence by signing the study informed consent
Who cannot join
- Prior history of chronic infectious disease, including tuberculosis, severe fungal disease, or known HIV positive
- Chronic hepatitis B or C infection
- Interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. Chest x-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis.
- Prior history of non basal cell malignancy or myeloproliferative or lymphoproliferative disease within the past 5 years
- White blood cell count <3,500/mm3, hematocrit <32%, or platelet count <75000/mm3
- Liver transaminase levels (AST/ALT) greater than the upper limit of normal or albumin less than the lower limit of normal
Show all 21Show fewer
- Creatinine clearance (CrCl) <40 mL/min as estimated by the Cockcroft-Gault equation
- History of alcohol abuse or unwillingness to limit alcohol consumption to <4 drinks per week
- Women of child bearing potential, even if currently using contraception, and women intending to breastfeed
- Men who plan to father children during the study period or who are unwilling to use contraception
- Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazoyl) or reduce tubular excretion (probenecid) or known allergies to antibiotics making avoidance of trimethoprim impossible
- Current indication for methotrexate therapy
- Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers
- Known chronic pericardial effusion, pleural effusion, or ascites
- New York Heart Association class IV congestive heart failure
- Life expectancy of <3 years
- The study population for the ancillary study will be the same as the main trial with the following additional exclusion criteria
- Subjects with a history of multiple imaging studies associated with radiation exposure
- Insulin-dependent diabetics
- If subject is Type 2 diabetic, hemoglobin A1c greater than 8% as determined by patient medical record review in the one year prior to the date of consent to this study.
- BMI greater than 37 kg/m2 or weight greater than 350 pounds
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02199
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Cardiovascular Inflammation Reduction Trial (CIRT) - Inflammation Imaging Study
Vascular inflammation, a central feature of atherosclerosis, participates in the initiation, perpetuation and instability of plaques. Multiple clinical trials of cholesterol lowering therapy with statins have demonstrated that reductions in atherosclerotic cardiovascular disease (CVD) events are associated with reductions in both LDL cholesterol (LDL-C) and the systemic inflammatory mediator C-reactive protein (CRP). The Cardiovascular Inflammation Reduction Trial (CIRT) investigates if an anti-inflammatory agent commonly used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CV morbidity and mortality among patients with a prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease (GCO#13-1467).
In this ancillary CIRT imaging study, the investigators propose to use this well validated approach by non-invasive serial FDG-PET/CT imaging in a subset of patients enrolled in the main CIRT trial to directly visualize vascular inflammation. Once the subjects are enrolled in the main CIRT trial, baseline imaging will be done and follow up imaging will be done approximately 8 months after the baseline imaging.
18FDG-PET imaging data will be acquired, analyzed centrally and results incorporated into the main CIRT database. The investigators hypothesize that LDM treatment will result in a significant decrease in plaque inflammation as measured by 18-FDG-PET/CT after 8 months as compared to placebo.
Read the detailed description
The NHLBI funded (Ridker 5U01HL101422) Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity to investigate whether a commonly used anti-inflammatory agent used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CVD morbidity and mortality among patients with stable coronary artery disease. CIRT, is a randomized, double-blind, placebo-controlled, multi-center trial among 7,000 men and women with prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease. Eligible participants will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM (average dose of 15-20 mg po/weekly. CIRT proposes that the reduction in CVD events with methotrexate derives from its effect on vascular inflammation, thus it is crucial to incorporate a measure of vascular inflammation imaging for confirmation of the primary mechanism of action underlying CIRT. As such, the direct evaluation of arterial inflammation would enhance the scientific value of the CIRT trial.
The inclusion of the proposed vascular inflammation imaging substudy has widespread implications that will allow this imaging modality to serve as a surrogate measure of disease, and thereby provide an opportunity for stratification in individuals at risk for CVD and evaluation of other interventions with presumed anti-inflammatory effects.
- Being tested
- Low dose methotrexate, Placebo
- Keywords
- Atherosclerotic cardiovascular disease, Inflammation reduction
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose methotrexateDrug
Study participants will additionally receive 1 mg daily oral folate.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Low dose methotrexate | Experimental | average dose of 15-20 mg po/weekly Receives: Drug: Low dose methotrexate |
| Placebo | Placebo comparator | matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Arterial Inflammation
Change in arterial inflammation - The relative change at 8 months as compared to baseline in arterial inflammation as measured by the most diseased segment (MDS) of the index vessel. The MDS is defined as the 1.5 cm segment within the carotid artery (right or left carotid) that demonstrates the highest PET/CT activity, and is calculated as a mean of maximum TBR values derived from 3 contiguous axial segments. The index vessel in turn is defined as the vessel (either aorta, right, or left carotid) with the greatest mean TBR at baseline. (MDS TBR Index Vessel)
Measured: baseline and 8 months
Secondary outcomes (2)
Change in Max Target-to-background (TBR)
Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid) at follow up imaging as compared to baseline.
Measured: baseline and 8 months
Change in Max TBR Within the Carotid Arteries
Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid)
Measured: baseline and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study start18 Dec 2015
- Primary completion29 Mar 2019
- Study completion29 Mar 2019
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 Vascular InflammationStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Unity Health Toronto, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Zahi Fayad, Icahn School of Medicine at Mount Sinai
- Investigators
- Zahi Fayad, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576067
- Sponsor's protocol ID
- GCO 14-1382
- Other IDs
- 1R01HL128056-01A1
- Acronym
- CIRT
- Status last verified
- Apr 2020
- First submitted
- 13 Oct 2015
- Last updated
- 20 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Inflammation Reduction Trial (CIRT) - Inflammation Imaging Study
- ClinicalTrials.gov ID
- NCT02576067
- Acronym / sponsor ID
- CIRT / GCO 14-1382
- Keywords
- Atherosclerotic cardiovascular disease, Inflammation reduction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Unity Health Toronto, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 18 Dec 2015 (actual)
- Primary completion
- 29 Mar 2019 (actual)
- Study completion
- 29 Mar 2019 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Posted 20 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vascular inflammation, a central feature of atherosclerosis, participates in the initiation, perpetuation and instability of plaques. Multiple clinical trials of cholesterol lowering therapy with statins have demonstrated that reductions in atherosclerotic cardiovascular disease (CVD) events are associated with reductions in both LDL cholesterol (LDL-C) and the systemic inflammatory mediator C-reactive protein (CRP). The Cardiovascular Inflammation Reduction Trial (CIRT) investigates if an anti-inflammatory agent commonly used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CV morbidity and mortality among patients with a prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease (GCO#13-1467).
In this ancillary CIRT imaging study, the investigators propose to use this well validated approach by non-invasive serial FDG-PET/CT imaging in a subset of patients enrolled in the main CIRT trial to directly visualize vascular inflammation. Once the subjects are enrolled in the main CIRT trial, baseline imaging will be done and follow up imaging will be done approximately 8 months after the baseline imaging.
18FDG-PET imaging data will be acquired, analyzed centrally and results incorporated into the main CIRT database. The investigators hypothesize that LDM treatment will result in a significant decrease in plaque inflammation as measured by 18-FDG-PET/CT after 8 months as compared to placebo.
Detailed description
The NHLBI funded (Ridker 5U01HL101422) Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity to investigate whether a commonly used anti-inflammatory agent used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CVD morbidity and mortality among patients with stable coronary artery disease. CIRT, is a randomized, double-blind, placebo-controlled, multi-center trial among 7,000 men and women with prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease. Eligible participants will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM (average dose of 15-20 mg po/weekly. CIRT proposes that the reduction in CVD events with methotrexate derives from its effect on vascular inflammation, thus it is crucial to incorporate a measure of vascular inflammation imaging for confirmation of the primary mechanism of action underlying CIRT. As such, the direct evaluation of arterial inflammation would enhance the scientific value of the CIRT trial.
The inclusion of the proposed vascular inflammation imaging substudy has widespread implications that will allow this imaging modality to serve as a surrogate measure of disease, and thereby provide an opportunity for stratification in individuals at risk for CVD and evaluation of other interventions with presumed anti-inflammatory effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose methotrexate | Experimental | Drug: Low dose methotrexateaverage dose of 15-20 mg po/weekly |
| Placebo | Placebo comparator | Drug: Placebomatching placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 18 years at screening
- Documented MI in the past or past evidence of multivessel coronary artery disease by angiography must have completed any planned coronary revascularization procedures associated with the qualifying event, and must be clinically stable for at least 60 d before screening; the qualifying prior MI must be documented either by hospital records or by evidence on current electrocardiogram of Q waves in 2 contiguous leads and/or an imaging test demonstrating wall motion abnormality or scar; the qualifying documentation of multivessel coronary disease must include angiographic evidence of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis.
- History of type 2 diabetes or metabolic syndrome at the time of study enrollment
- Willing to participate as evidence by signing the study informed consent
Key exclusion criteria (21 listed)
- Prior history of chronic infectious disease, including tuberculosis, severe fungal disease, or known HIV positive
- Chronic hepatitis B or C infection
- Interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. Chest x-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis.
- Prior history of non basal cell malignancy or myeloproliferative or lymphoproliferative disease within the past 5 years
- White blood cell count <3,500/mm3, hematocrit <32%, or platelet count <75000/mm3
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 |
|---|---|---|
| Low dose methotrexateStudy participants will additionally receive 1 mg daily oral folate. | Drug | Low dose methotrexate |
| Placebo | Drug | Placebo |
Primary outcome
Change in Arterial Inflammation
Time frame: baseline and 8 months
Change in arterial inflammation - The relative change at 8 months as compared to baseline in arterial inflammation as measured by the most diseased segment (MDS) of the index vessel. The MDS is defined as the 1.5 cm segment within the carotid artery (right or left carotid) that demonstrates the highest PET/CT activity, and is calculated as a mean of maximum TBR values derived from 3 contiguous axial segments. The index vessel in turn is defined as the vessel (either aorta, right, or left carotid) with the greatest mean TBR at baseline. (MDS TBR Index Vessel)
2 secondary outcomes
Change in Max Target-to-background (TBR)
Time frame: baseline and 8 months
Change in Max TBR Within the Carotid Arteries
Time frame: baseline and 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2020.
- 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.
Zahi Fayad, PhD principal investigator
Icahn School of Medicine at Mount Sinai
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Low dose methotrexate in people with Vascular Inflammation and Atherosclerotic Cardiovascular Disease, run by Icahn School of Medicine at Mount Sinai at 3 sites in 2 countries.
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 4 inclusion and 21 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 20 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 20 Apr 2020). 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 Arterial Inflammation (time frame: baseline and 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2020.