Clinical trial NCT04181749: Peri-vascular Adipose Tissue Inflammation Evaluated Using Coronary CT Angiography
Official title: Peri-vascular Adipose Tissue Inflammation Evaluated Using Coronary CT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cardiovascular Risk Factor
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: British Heart Foundation
name: National Institute for Health Research, United Kingdom
First posted: 2019-11-29
Enrollment: 200
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients randomized to No treatment or Aspirin and Statin
Primary purpose: DIAGNOSTIC

Brief summary: The P-VECT Study proposes to test the use of CCTA-derived FAI measurements in a group of patients with coronary artery inflammation, who will receive routinely-used statin and aspirin treatment. The P-VECT Study is a pilot study that will provide the rationale and data for power calculations to enable design of pivotal trials of the clinical effectiveness of FAI.

Detailed description: In this research we will study the ability of coronary CT angiography (CCTA)- derived Fat Attenuation Index (FAI) measurements to detect changes in coronary artery inflammation following treatment with atorvastatin and aspirin . CT scan images are used to evaluate the presence of atherosclerotic plaque in the wall of the coronary arteries. The new CCTA technique, FAI, detects and quantifies coronary artery inflammation by analysis of the characteristics of the adipose tissue (fat) around the wall of the artery - the peri-vascular adipose tissue (PVAT) This is a pilot study, involving patients undergoing a clinically indicated CCTA as part of their routine clinical care who are shown (on their scans) to have mild coronary artery plaques (\<50% luminal stenosis) with a high FAI value (\>70.1 HU). Patients will have 6 visits (one of which screening) with hospital attendance on 3 occasions for blood tests and drug supply. The pilot study will provide the rationale for power calculations from which further studies can be developed to evaluate the clinical effectiveness of FAI.

Eligibility criteria: Inclusion Criteria:

Participants must satisfy the following conditions:

1. Male or Female, aged 30 to 80 years,
2. CCTA scan showing mild coronary artery plaques (\<50% luminal stenosis) with a high FAI value (\>70.1 HU) within last 3 months.
3. No definite clinical indication for statin treatment (i.e. do not have either cholesterol \>6.5 mM, or cholesterol \>5.0 mM and QRISK score \>10%).
4. Clinical equipoise for statin and aspirin treatment, as determined by the local treating physician. In these patients, there is clinical equipoise because routine treatment with aspirin and statin is not mandated by current guidelines, but the presence of minor coronary artery plaques is frequently interpreted by clinicians as an indication for aspirin and statin treatment. Accordingly, some patients in this group typically receive aspirin and statin treatment, whereas others do not.
5. Willing and able (in the Investigators opinion) to comply with all study requirements.
6. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of any incidental findings.
7. Able to understand both verbal or written English

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Exclusion Criteria:

* The participant may not enter the study if ANY of the following are known to apply:

  1. Previous documented history of coronary artery disease requiring treatment. This includes any of the following:

     Acute myocardial infarction Unstable angina Coronary revascularization procedure Clinically significant coronary artery disease diagnosed by invasive or non-invasive testing.
  2. Known diabetes mellitus
  3. Definite clinical indication for statin treatment (i.e. has either cholesterol \>6.5 mM, or cholesterol \>5.0 mM and QRISK score \>10%).
  4. Treatment with aspirin, statin or any prescribed lipid modification therapy in 6 weeks before baseline CCTA
  5. Atrial fibrillation (paroxysmal or persistent)
  6. History of New York Heart Association (NYHA) Class III or IV heart failure within the past 12 months of consent.
  7. Autoimmune disease requiring immunosuppressive therapy or systemic corticosteroid therapy
  8. Active treatment with any anti-inflammatory agents (e.g. NSAIDs, corticosteroids)
  9. Active neoplasm requiring surgery, chemotherapy, or radiation within the prior 12 months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to screening with no detectable recurrence are allowed)
  10. Contraindication for aspirin and/or statin therapy
  11. Severe Chronic kidney disease (estimated glomerular filtration rate \< 30 mL/min/1.73 m² and/or serum creatinine \> 2.5 mg/dL or 220 µmol/l).
  12. Hepatic dysfunction (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \> 3 × the upper limit of normal \[ULN\] measured on local labs in last 6 months)
  13. Any clinically significant abnormality identified at the time of screening that, in the opinion of the Investigator, would preclude safe completion of the study.
  14. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
  15. Participants who have participated in another research study involving a treatment intervention or an investigational product, in the past 12 weeks.
  16. Patients unable to understand verbal or written English.
  17. Contraindication to contract dye for CCTA.
  18. Pregnancy

Primary outcomes:
measure: Evaluate ability of new coronary CT angiogram (CCTA) scan biomarker- Fat Attenuation Index (FAI).
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
Secondary outcomes:
measure: Evaluate the association between changes in Fat Attenuation Index (FAI) and plasma lipid parameters.
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
measure: Evaluate the association between changes in Fat Attenuation Index (FAI) and plasma lipid parameters.
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
measure: Evaluate the association between changes in Fat Attenuation Index (FAI) and plasma lipid parameters.
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
measure: Evaluate the association between changes in FAI and plasma biomarkers of inflammation.
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
measure: Evaluate the association between changes in FAI and plasma biomarkers of inflammation.
timeFrame: 3year study- Two years recruitment with 8 month patient follow up
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester
city: London
country: United Kingdom
facility: Royal Brompton Hospitals Trust
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: University Hospitals of Leicester and University of Leicester
name: David Adlam, Dr.
role: PRINCIPAL_INVESTIGATOR
References: