Clinical trial NCT06478277: UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry Study
Official title: The UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) Registry
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cardiovascular Diseases
Immune-Mediated Inflammatory Diseases
Keywords: Cardiovascular disease
Immune-mediated Inflammatory Diseases
Registry
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: University of Cambridge
name: University of Oxford
name: University of Edinburgh
name: University of Leeds
name: Imperial College London
name: Medical Research Council
name: British Heart Foundation
name: Swansea University
name: British Heart Foundation Data Science Centre
First posted: 2024-06-27
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be recruited from NHS secondary care in the United Kingdom. Potential participants may be identified from clinics, wards, diagnostic pathways and departments, electronic and paper-based health records, databases and waiting lists in secondary care. All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation, except where the study inclusion and exclusion criteria explicitly state otherwise.

Brief summary: The goal of this observational study is to develop a large, deeply characterised cohort that will be a platform for collaborative clinical and translational research into cardiovascular (CV) disease (CVD) and Immune-mediated-inflammatory-diseases (IMID). The main aim is to evaluate whether existing blood cardiac biomarkers predict adverse cardiovascular outcomes. The study will capture standard of care CV and associated health data (clinical, biochemistry/pathology and investigations) in patients across the IMIDs. Optional biological and/or imaging sub-studies will provide additional data and/or samples for associated analyses.

Detailed description: Multimorbidity is a rapidly growing burden on our healthcare systems, especially with an ageing demographic. CVD is a major cause of morbidity and mortality. The co-association of IMIDs with CVD needs more sophisticated understanding of the underlying risk, earlier identification and tailored use of targeted therapeutics. Importantly, the investigation of CVD in IMID offers an effective human experimental model to improve not just the lives of people with IMIDs but also the general CVD population.

The UK CARDIOvascular Immune-Mediated Inflammatory Diseases (CARDIO-IMID) registry will be a key platform for United Kingdom (UK) multi-centre clinical and translational CARDIO-IMID research. The aim is that centres across the UK including all the devolved nations will collaborate and contribute patients such that the registry will provide deep phenotyping, linked to clinical outcomes, in, ultimately, many hundreds of patients. The planned study will establish a deeply phenotyped cohort and/or as part of the optional sub-study, an associated bioresource to support individual discrete studies and/or analyses that address the stated aims and objectives. All potential participants will be invited to participate in the longitudinal collection and evaluation of routine comprehensive clinical information, including pathology, imaging and other cardiovascular data. This programme will identify patients within defined IMID clinical cohorts at different stages of (rheumatology and cardiovascular) disease. These data will be invaluable in enabling a full characterisation of CVD in terms of the extent, presentation, risk factors, and pathophysiology. Patients are seen as per standard clinical practice determined by the index IMID and in this setting, also dependent on co-existing CV comorbidity, usually every 3-6 months at time of IMID/CVD diagnosis and then 6 to 12 monthly thereafter. Specific questionnaires and tests requested outside of standard of care (sub-studies) will depend on disease group and clinical context. Not all patients will be required to complete all the relevant questionnaires, instead, based on individual IMID and/or CVD profile.

In addition, there is the opportunity for subjects to include (i) longitudinal biological (blood) samples and (ii) extended cardiovascular magnetic resonance (CMR) imaging protocol for those receiving CMR as part of National Health Service (NHS) standard of care.

Collectively, the study and associated platform with appropriate biostatistical and machine learning approaches will inform on the pathophysiological sequence of events, identification of prognostic biomarkers and risk models; as well as enable evaluation of the influence of IMID-specific vascular +/- immunosuppressive therapies and traditional cardiac pharmacotherapy where indicated. It will also establish a platform for trials in IMIDs to capture CV outcomes. Moreover, it will provide cohorts of patients readily available for recruitment, with linkage in place for outcomes. It could be used to leverage commercial funding and participation, facilitated by simplified, single-point access for industry. It will enable scaled investigation aimed at understanding causes of CARDIO-IMID, improving risk stratification and providing better care.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent
2. Diagnosis of an IMID by a rheumatologist with categorisation into one of the following:

   i. IMID-'higher risk' CVD: individuals who have a risk of developing CVD (based on traditional risk factors and/or IMID-specific factors) but no history of CVD
   1. Coronary artery disease (CAD): specifically, a high pre-test probability of CAD based on clinical risk factors (e.g. QRISK3 score ≥10%) and/or elevated biochemical markers (high-sensitivity C-reactive protein ≥2mg/L and/or Lipoprotein(a) ≥70mg/dL)
   2. Myopericardial involvement: Specific IMID and/or cardiovascular indicators that place at increased risk e.g. autoantibody associations, presence of peripheral myositis or other major organ involvement; incidental raised serum cardiac biomarkers (troponin and/or NT-pro BNP), on routine testing

      ii. Incident (new) IMID-CVD: Patients with IMID that present with a new history of CVD

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   1. ASCVD i. Major adverse cardiovascular events (MACE):

      - Non-fatal myocardial infarction.

      - Non-fatal stroke of any classification, including reversible focal neurologic

      - Defects with imaging evidence of a new cerebral lesion consistent with ischemia or haemorrhage.

      ii. Other cardiovascular events not accounted for in the MACE-3 composite 2)a)i:

      - Hospitalization for unstable angina

      - Coronary revascularization

      - Hospitalization for heart failure

      - Transient Ischemic Attack (TIA)

      - Peripheral Vascular Disease (PVD)
      * Deep vein thrombosis (VTE) and/or pulmonary embolism \[PE\].
   2. Myopericardial involvement: as diagnosed by a cardiology specialist with 'tier 2' cardiovascular imaging and/or other clinical and biochemical criteria in line with usual care

      iii. Established IMID-CVD

   a) Patients with IMID and a history of past cardiovascular event as detailed in 2) a) above.

   b) Patients with a known history of myopericardial involvement as defined above in 2) b)

Biological sub-study inclusion criteria

* There are no additional inclusion criteria for this sub-study

Extended protocol standard CMR sub-study inclusion criteria.

* Participants that receive a CMR scan as standard of care

Exclusion Criteria:

1. Age less than 18 years
2. Unable to give informed consent

Biological sub-study exclusion criteria:

- There are no additional exclusion criteria for this sub-study

CMR sub-study exclusion criteria:

Standard of care contraindications to:

1. CMR: metal implant eg metal fragments in the eye, pacemaker; claustrophobia; inability to lie flat
2. Magnetic Resonance Imaging (MRI) contrast: renal failure with estimated glomerular filtration rate (eGFR) \<30,

Primary outcomes:
measure: Number of participants with abnormal high-sensitivity cardiac troponin I/T levels
timeFrame: 5 years
measure: Number of participants with abnormal N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels
timeFrame: 5 years
Secondary outcomes:
measure: Number of participants with atherosclerotic cardiovascular disease (ASCVD)
timeFrame: 5 years
measure: Number of participants with myopericardial involvement
timeFrame: 5 years
measure: Number of participants with other cardiovascular events
timeFrame: 5 years
measure: Atrial and ventricular volumetrics
timeFrame: 5 years
measure: Systolic and diastolic function
timeFrame: 5 years
measure: Abnormalities in regional wall motion
timeFrame: 5 years
measure: Global longitudinal strain
timeFrame: 5 years
measure: T2 relaxation time
timeFrame: 5 years
measure: Late gadolinium enhancement
timeFrame: 5 years
measure: T1 relaxation time
timeFrame: 5 years
measure: Extracellular volume fraction
timeFrame: 5 years
measure: Aortic distensibility
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Manchester
name: Maya H Buch, MD
role: PRINCIPAL_INVESTIGATOR
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