Coronary Heart DiseaseCIRT-CFRNCT02786134
Coronary Flow Reserve to Assess Cardiovascular Inflammation (CIRT-CFR)
A study testing PET scan and Echocardiogram in people with Coronary Heart Disease and Metabolic Syndrome, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Coronary flow reserve (CFR, calculated as the ratio of hyperemic over rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Coronary Heart Disease, Metabolic Syndrome, Diabetes Mellitus
- What is being tested?
- PET scan and Echocardiogram
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Oct 2019
- Phase
- Interventional
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years at screening;
- Documented past history of MI OR past evidence of multivessel CAD by angiography, completed any planned coronary revascularization associated with a qualifying event at least 60 days prior to enrollment, and clinically stable for ≥60 days prior to enrollment; qualifying prior MI must be documented either by hospital records, evidence on current ECG of Q waves in 2 contiguous leads, and/or an imaging test demonstrating wall motion abnormality or scar; qualifying evidence of multivessel CAD by angiography must be documented by CAD in at least two major epicardial vessels defined either as the presence of a stent, a coronary artery bypass graft, or an angiographic lesion of 60% or greater (left main CAD 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 DM or metabolic syndrome (meeting 2004 AHA/NHLBI definition*) at time of study enrollment; *includes any 3 of the following 5 diagnostic criteria: waist circumference ≥ 102 cm in men or 88 cm in women; triglycerides ≥ 150 mg/dl or on drug treatment for elevated triglycerides; high-density lipoprotein cholesterol (HDL-C)< 40 mg/dL in men or < 50 mg/dL in women or on drug treatment for reduced HDL-C; systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg or on drug treatment for hypertension; and elevated fasting glucose ≥ 100 mg/dL or on drug treatment for elevated glucose.
- Willingness to participate as evidenced by signing the CIRT and CIRT-CFR informed consent.
Who cannot join
- Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of <3 years;
- Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease
- White blood cell count <3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul
- Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN);
- Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation;
- History of alcohol abuse or unwillingness to limit alcohol consumption to less than 4 drinks per week
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- Women of child bearing potential, even if they are currently using contraception, and women intending to breastfeed.
- Men who plan to father children during the study period or who are unwilling to use effective forms of contraception.
- Requirement for use of drugs that alter folate metabolism (trimethoprim/sulfamethoxazol) 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 (see Exclusionary Medication List in Manual of Operations). Eligible study participants will be encouraged to have up to date pneumococcal and influenza vaccinations as recommended based on their age and underlying medical conditions.
- Chest X-ray evidence in the past 12 months of interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis. For participants who do not have a chest X-ray in the prior 12 months, a chest X-ray will be obtained at baseline as part of the study protocol.
- New York Heart Association Class IV congestive heart failure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Coronary flow reserve (CFR, calculated as the ratio of hyperemic over rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities, affecting the entire coronary vasculature, but no clinical trial to date has shown that directly reducing inflammation lowers cardiovascular event rates. As such, the recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in patients at high-risk of events. The investigators are ideally positioned to examine the impact of inflammation on CFR, having extensive experience in both the quantitation of CFR using clinically-integrated dynamic positron emission tomography (PET) and the ability to assess its association with cardiovascular outcomes. The central hypothesis of this ancillary proposal, CIRT-CFR, is that reducing systemic inflammation using low-dose methotrexate (LDM) will, compared to placebo, quantitatively improve myocardial blood flow and coronary flow reserve as measured by PET over one year, in stable CAD patients with type 2 diabetes or metabolic syndrome enrolled in CIRT. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis.
Read the detailed description
Randomization and double-blind study treatment period to either placebo or LDM (1:1) of willing and eligible patients will occur at the end of the open label run-in phase per the parent CIRT protocol, and will be stratified by time since the qualifying event (< 6 or ≥ 6 months from the date of MI or most recent angiogram), type of event (MI or multivessel CAD), presence of either type 2 DM or metabolic syndrome, and site, which will ensure balance in the proposed study. Patients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline PET scan along with echocardiography at any point between the parent CIRT post run-in visit (Visit 3) and up to 4 weeks after randomization (Visit 4).
Imaging will be performed at the 3 imaging centers (BWH, OHI, and UAB). To minimize participant and site burden, only a baseline and single follow-up imaging time point will be pursued. Imaging tests (PET and echo) will be scheduled on the same day for patient convenience if possible, and no more than one week apart. "Baseline" study visit imaging will follow the open label run-in period of the parent trial to enhance long-term compliance and eliminate risk of radiation exposure for any individuals with immediate intolerance to the LDM study protocol. The imaging tests proposed are non-invasive, routinely performed, and historically well tolerated by patients.
- Being tested
- PET scan, Echocardiogram
- Medical subject headings
- Coronary Disease, Metabolic Syndrome, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET scanRadiation
A cardiac PET scan will be performed at baseline (main CIRT trial randomization) and at 12-months.
EchocardiogramRadiation
An echocardiogram will be performed at baseline (main CIRT trial randomization) and at 12-months.
| Study group | Role | What they receive |
|---|---|---|
| low-dose methotrexate (LDM) | Experimental | Patients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline rest/dipyridamole stress PET scan along with echocardiography. The final PET scan and echocardiogram will occur at approximately 12 months after randomization. Receives: Radiation: PET scan; Radiation: Echocardiogram |
| placebo | Experimental | Patients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline rest/dypridamole stress PET scan along with echocardiography. The final PET scan and echocardiogram will occur at approximately 12 months after randomization. Receives: Radiation: PET scan; Radiation: Echocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Global Myocardial Blood Flow in Response to Vasodilator
Change (from baseline) in global coronary flow reserve in response to vasodilator as measured by PET imaging at baseline and at one year
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2016 (estimated)
- Study startApr 2016
- Primary completionOct 2019
- Study completionOct 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The CIRT-CFR study is a sub-study based off the main CIRT trial.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02786134
- Sponsor's protocol ID
- 2013P002186
- Acronym
- CIRT-CFR
- Status last verified
- Dec 2020
- First submitted
- 20 May 2016
- Last updated
- 6 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated device
- No
Publications
Taqueti VR, Shah AM, Everett BM, Pradhan AD, Piazza G, Bibbo C, Hainer J, Morgan V, Carolina do A H de Souza A, Skali H, Blankstein R, Dorbala S, Goldhaber SZ, Le May MR, Chow BJW, deKemp RA, Hage FG, Beanlands RS, Libby P, Glynn RJ, Solomon SD, Ridker PM, Di Carli MF. Coronary Flow Reserve, Inflammation, and Myocardial Strain: The CIRT-CFR Trial. JACC Basic Transl Sci. 2022 Dec 21;8(2):141-151. doi: 10.1016/j.jacbts.2022.08.009. eCollection 2023 Feb.
PubMed 36908662
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Coronary Flow Reserve to Assess Cardiovascular Inflammation (CIRT-CFR)
- ClinicalTrials.gov ID
- NCT02786134
- Acronym / sponsor ID
- CIRT-CFR / 2013P002186
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Ottawa Heart Institute Research Corporation, University of Alabama at Birmingham
- Study start
- Apr 2016 (actual)
- Primary completion
- Oct 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 30 May 2016 (estimated)
- Results
- Posted 6 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronary flow reserve (CFR, calculated as the ratio of hyperemic over rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities, affecting the entire coronary vasculature, but no clinical trial to date has shown that directly reducing inflammation lowers cardiovascular event rates. As such, the recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in patients at high-risk of events. The investigators are ideally positioned to examine the impact of inflammation on CFR, having extensive experience in both the quantitation of CFR using clinically-integrated dynamic positron emission tomography (PET) and the ability to assess its association with cardiovascular outcomes. The central hypothesis of this ancillary proposal, CIRT-CFR, is that reducing systemic inflammation using low-dose methotrexate (LDM) will, compared to placebo, quantitatively improve myocardial blood flow and coronary flow reserve as measured by PET over one year, in stable CAD patients with type 2 diabetes or metabolic syndrome enrolled in CIRT. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis.
Detailed description
Randomization and double-blind study treatment period to either placebo or LDM (1:1) of willing and eligible patients will occur at the end of the open label run-in phase per the parent CIRT protocol, and will be stratified by time since the qualifying event (< 6 or ≥ 6 months from the date of MI or most recent angiogram), type of event (MI or multivessel CAD), presence of either type 2 DM or metabolic syndrome, and site, which will ensure balance in the proposed study. Patients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline PET scan along with echocardiography at any point between the parent CIRT post run-in visit (Visit 3) and up to 4 weeks after randomization (Visit 4).
Imaging will be performed at the 3 imaging centers (BWH, OHI, and UAB). To minimize participant and site burden, only a baseline and single follow-up imaging time point will be pursued. Imaging tests (PET and echo) will be scheduled on the same day for patient convenience if possible, and no more than one week apart. "Baseline" study visit imaging will follow the open label run-in period of the parent trial to enhance long-term compliance and eliminate risk of radiation exposure for any individuals with immediate intolerance to the LDM study protocol. The imaging tests proposed are non-invasive, routinely performed, and historically well tolerated by patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The CIRT-CFR study is a sub-study based off the main CIRT trial.
| Arm | Type | Receives |
|---|---|---|
| low-dose methotrexate (LDM) | Experimental | Radiation: PET scan, Radiation: EchocardiogramPatients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline rest/dipyridamole stress PET scan along with echocardiography. The final PET scan and echocardiogram will occur at approximately 12 months after randomization. |
| placebo | Experimental | Radiation: PET scan, Radiation: EchocardiogramPatients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline rest/dypridamole stress PET scan along with echocardiography. The final PET scan and echocardiogram will occur at approximately 12 months after randomization. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years at screening;
- Documented past history of MI OR past evidence of multivessel CAD by angiography, completed any planned coronary revascularization associated with a qualifying event at least 60 days prior to enrollment, and clinically stable for ≥60 days prior to enrollment; qualifying prior MI must be documented either by hospital records, evidence on current ECG of Q waves in 2 contiguous leads, and/or an imaging test demonstrating wall motion abnormality or scar; qualifying evidence of multivessel CAD by angiography must be documented by CAD in at least two major epicardial vessels defined either as the presence of a stent, a coronary artery bypass graft, or an angiographic lesion of 60% or greater (left main CAD 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 DM or metabolic syndrome (meeting 2004 AHA/NHLBI definition*) at time of study enrollment; *includes any 3 of the following 5 diagnostic criteria: waist circumference ≥ 102 cm in men or 88 cm in women; triglycerides ≥ 150 mg/dl or on drug treatment for elevated triglycerides; high-density lipoprotein cholesterol (HDL-C)< 40 mg/dL in men or < 50 mg/dL in women or on drug treatment for reduced HDL-C; systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg or on drug treatment for hypertension; and elevated fasting glucose ≥ 100 mg/dL or on drug treatment for elevated glucose.
- Willingness to participate as evidenced by signing the CIRT and CIRT-CFR informed consent.
Key exclusion criteria (13 listed)
- Prior history of chronic infectious disease, tuberculosis, or severe fungal disease; chronic hepatitis B or C infection; renal insufficiency; interstitial pneumonitis, bronchiectasis, or pulmonary fibrosis; known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; non-basal cell malignancy or treated lymphoproliferative disease within the past 5 years; known HIV positive; life expectancy of <3 years;
- Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease
- White blood cell count <3,500/ul, hematocrit < 32 percent, or platelet count < 75,000/ul
- Liver transaminase levels (AST or ALT) >upper limit of normal (ULN) or albumin < the lower limit of normal (LLN);
- Creatinine clearance < 40 ml/min as estimated with the Cockroft-Gault equation;
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 |
|---|---|---|
| PET scanA cardiac PET scan will be performed at baseline (main CIRT trial randomization) and at 12-months. | Radiation | low-dose methotrexate (LDM), placebo |
| EchocardiogramAn echocardiogram will be performed at baseline (main CIRT trial randomization) and at 12-months. | Radiation | low-dose methotrexate (LDM), placebo |
Primary outcome
Change in Global Myocardial Blood Flow in Response to Vasodilator
Time frame: 12 months
Change (from baseline) in global coronary flow reserve in response to vasodilator as measured by PET imaging at baseline and at one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36908662Taqueti VR, Shah AM, Everett BM, Pradhan AD, Piazza G, Bibbo C, Hainer J, Morgan V, Carolina do A H de Souza A, Skali H, Blankstein R, Dorbala S, Goldhaber SZ, Le May MR, Chow BJW, deKemp RA, Hage FG, Beanlands RS, Libby P, Glynn RJ, Solomon SD, Ridker PM, Di Carli MF. Coronary Flow Reserve, Inflammation, and Myocardial Strain: The CIRT-CFR Trial. JACC Basic Transl Sci. 2022 Dec 21;8(2):141-151. doi: 10.1016/j.jacbts.2022.08.009. eCollection 2023 Feb.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET scan and Echocardiogram in people with Coronary Heart Disease and Metabolic Syndrome, run by Brigham and Women's Hospital 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 4 inclusion and 13 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 6 Jan 2021. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2021). 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 Global Myocardial Blood Flow in Response to Vasodilator (time frame: 12 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 NCT02786134, which also lists 1 linked publication.
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 6 Jan 2021.