- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04403607
Cardiac Imaging in SARS-CoV-2 (COVID-19) (CISCO-19)
Cardiovascular and Pulmonary Imaging in SARS-CoV-2: A Study of the Heart, Lungs and Wellbeing After COVID-19.
Study Overview
Status
Conditions
Detailed Description
Our study is supported through the Chief Scientist Office Rapid Research in Covid-19 (RARC-19) programme. Our study will clarify the pathogenesis of cardiopulmonary injury, notably endotypes of myocardial injury including myocarditis, in patients with COVID-19.
The study involves a prospective, observational, multicentre, longitudinal cohort design.The investigators aim to minimise selection bias by adopting consecutive screening of all-comers hospitalised with COVID-19 and the eligibility criteria are broad. For example, severe renal dysfunction is not an exclusion criterion. The sample size is 180 patients enrolled at baseline with 160 attending for the primary outcome evaluation (cardiac imaging) at 28 days post-discharge. The investigators will use advanced cardiovascular imaging to identify the number (proportion) of patients with myocardial inflammation (myocarditis) that is sub-clinical (i.e. not diagnosed) or clinically overt. Cardiovascular MRI and CT coronary angiography will provide a comprehensive examination one month after discharge is intended to detect persisting cardiovascular complications and diagnose clinical endotypes. The investigators aim to clarify the pathological significance of serial changes in circulating troponin, NTproBNP and renal function. By correlating the MRI findings with troponin I and other measures of cardiovascular injury, such as NTproBNP, our results will inform care pathways that use these blood tests to guide the management of patients with COVID-19. Correlation of imaging findings with baseline clinical information, biomarkers, patient reported outcome measures and well-being in the longer term will help to clarify the clinical significance of cardiovascular complications in COVID-19. Since the design is observational, an interim analysis may be undertaken with the timing informed by the enrolment rate.
Longer term follow-up will include a 5-year visit, contingent on funding and ethics approval, and electronic health record linkage of vital status and episodes of NHS care.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Glasgow, United Kingdom, G51 4TF
- Queen Elizabeth University Hospital
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Glasgow, United Kingdom, G31 2ER
- Royal Infirmary
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Renfrewshire
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Paisley, Renfrewshire, United Kingdom, PA2 9PJ
- Royal Alexandra Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- History of hospital attendance or hospitalisation for COVID-19, confirmed by a clinical diagnosis, laboratory test e.g. PCR and/or a radiological test e.g. CT chest or chest X-ray
- Age 18 years or more
- Capacity to provide written informed consent
- Able to comply with study procedures
Exclusion Criteria:
- Contra-indication to CMR e.g. severe claustrophobia, metallic foreign body
- Lack of informed consent
- Women who are pregnant, breast-feeding or of child-bearing potential without a negative pregnancy test
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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COVID-19
Patients with confirmed COVID-19 meeting the eligibility criteria specified in the protocol.
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Control
COVID-19 negative.
Age/sex matched to the COVID-19 cohort.
Age range 40-80 years.
At least one cardiovascular risk factor by ASSIGN criteria.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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The primary cardiac outcome is the proportion of patients with a diagnosis of myocardial inflammation (myocarditis).
Time Frame: 28 days after discharge from hospital
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Myocardial inflammation (or myocarditis) will be revealed by cardiovascular magnetic resonance imaging (MRI) according to contemporary guidelines including the modified Lake Louise Criteria.
The endotypes of myocardial injury are 1) myocardial inflammation due to 1.1) viral myocarditis, 1.2) ischaemia, or 1.3) stress (Takotsubo) cardiomyopathy, 2) myocardial infarction, 3) indeterminate, or 4) none.
The final diagnosis will be a consensus-based determination by an expert panel.
This information will provide insights into the incidence, nature, time-course and clinical significance of cardiovascular involvement in patients with COVID-19.
The clinical significance of our findings will be assessed through associations with patient reported outcome measures (PROMS) and health outcomes in the longer term.
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28 days after discharge from hospital
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The primary cardio-pulmonary outcome is the proportion of patients with thrombosis
Time Frame: 28 days after discharge from hospital
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Thrombosis of the right heart, pulmonary arteries and left heart will be determined contrast-enhanced CT chest, angiography and MRI.
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28 days after discharge from hospital
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Myocardial injury
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess mechanisms using circulating biomarkers of cardiac injury, high sensitivity troponin I (ng/L) and its change over time from baseline.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Myocardial stress
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess the significance of myocardial injury by measuring circulating concentrations of NTproBNP (pg/mL) and its change over time from baseline.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Systemic inflammation
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess systemic inflammation by measurement of the peak circulating concentration of C-reactive protein (mg/dL) and its change over time.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Vascular injury
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess vascular injury/inflammation by measurement of the peak circulating concentration of IL-6 (pg/mL) and its change over time.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Endothelial activation and haemostasis
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess endothelial injury by immunoassay measurement of the peak circulating concentration of VWF:ag (IU/dL) and its change over time.
Other measures of haemostasis will also be measured.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Fibrin lysis
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess fibrin lysis by measurement of the peak circulating concentration of fibrin D-dimer (IU/dL) and its change over time.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Coagulation
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess coagulation by measurement of Activated Partial Thromboplastin Time (APTT) in seconds.
Other measures of coagulation will also be measured.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Platelet count
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess platelet count (n/microlitre), minimum value (thrombocytopaenia) and change over time.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Renal function
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Assess renal function using urine albumin:creatinine ratio and its change over time.
Other measures of renal function/injury will also be assessed.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Quantify myocardial perfusion as a measure of coronary microvascular function
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Stress perfusion MRI will provide quantitative assessments of myocardial perfusion (ml/min/g) and classify perfusion abnormalities according to other MRI findings e.g.
scar, inflammation and coronary artery disease as revealed by CT coronary angiography.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Association of the primary outcome according to a prior history of cardiovascular disease or no history of prior cardiovascular disease.
Time Frame: 28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Imaging for coronary disease, PTE and lung pathology will be correlated with NHS clinical data on prior history of cardiovascular disease.
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28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
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Patient reported outcome measures (PROMS) - health status
Time Frame: 1 year
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Health status, well being and function will be prospectively assessed using prespecified PROMS : EuroQOL EQ-5D-5L score.
Other measures of health status will also be assessed.
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1 year
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PROMS - functional capacity
Time Frame: 1 year
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Patient reported functional activity using the Duke Activity Status Index (DASI), measured by the score generated from the questionnaire (https://www.mdcalc.com/duke-activity-status-index-dasi)
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1 year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cardiovascular science - vascular biology
Time Frame: 1 year
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Exploratory study to help better understand the cardiovascular pathophysiology of COVID-19.
The outcome is endothelial function in of isolated arterioles from gluteal biopsy.
Endothelial function will be the (Emax, % vasorelaxation to acetylcholine in a pre-constricted arteriole).
Other measures of vascular function will also be assessed.
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1 year
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Cardiovascular science - mathematical modelling
Time Frame: 1 year
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Exploratory study to help better understand the cardiac biomechanical implications of COVID-19.
The outcome measure will be myocardial stiffness (Cauchy stress, kPa).
The sub-studies will involve using mathematical modelling and, relatedly, statistical emulation.
The models will also include the coronary/pulmonary circulation.
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1 year
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Cardiovascular science - pathology
Time Frame: 1 year
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The pathogenesis of SARS-CoV-2 will be examined using histopathology techniques.
The outcome is SARS-CoV-2 viral protein or RNA identified in cardiovascular cells.
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1 year
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Health outcomes (serious adverse events)
Time Frame: 20 years
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Health outcomes as measured by the occurrence of serious adverse events (SAE) quantified by 1) rehospitalisation and 2) death.
These events will be identified in the longer term using electronic record linkage to health records held by government and the National Health Service.
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20 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Colin Berry, MBChB/PhD, University of Glasgow / NHS Greater Glasgow & Clyde
Publications and helpful links
General Publications
- Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
- Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, Madhur MS, Tomaszewski M, Maffia P, D'Acquisto F, Nicklin SA, Marian AJ, Nosalski R, Murray EC, Guzik B, Berry C, Touyz RM, Kreutz R, Wang DW, Bhella D, Sagliocco O, Crea F, Thomson EC, McInnes IB. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 Aug 1;116(10):1666-1687. doi: 10.1093/cvr/cvaa106.
- Cosyns B, Lochy S, Luchian ML, Gimelli A, Pontone G, Allard SD, de Mey J, Rosseel P, Dweck M, Petersen SE, Edvardsen T. The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients. Eur Heart J Cardiovasc Imaging. 2020 Jul 1;21(7):709-714. doi: 10.1093/ehjci/jeaa136.
- Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Helio T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.
- Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. No abstract available. Erratum In: Circulation. 2018 Nov 13;138(20):e652.
- Morrow AJ, Sykes R, McIntosh A, Kamdar A, Bagot C, Bayes HK, Blyth KG, Briscoe M, Bulluck H, Carrick D, Church C, Corcoran D, Findlay I, Gibson VB, Gillespie L, Grieve D, Hall Barrientos P, Ho A, Lang NN, Lennie V, Lowe DJ, Macfarlane PW, Mark PB, Mayne KJ, McConnachie A, McGeoch R, McGinley C, McKee C, Nordin S, Payne A, Rankin AJ, Robertson KE, Roditi G, Ryan N, Sattar N, Allwood-Spiers S, Stobo D, Touyz RM, Veldtman G, Watkins S, Weeden S, Weir RA, Welsh P, Wereski R; CISCO-19 Consortium; Mangion K, Berry C. A multisystem, cardio-renal investigation of post-COVID-19 illness. Nat Med. 2022 Jun;28(6):1303-1313. doi: 10.1038/s41591-022-01837-9. Epub 2022 May 23.
- Mangion K, Morrow A, Bagot C, Bayes H, Blyth KG, Church C, Corcoran D, Delles C, Gillespie L, Grieve D, Ho A, Kean S, Lang NN, Lennie V, Lowe DJ, Kellman P, Macfarlane PW, McConnachie A, Roditi G, Sykes R, Touyz RM, Sattar N, Wereski R, Wright S, Berry C. The Chief Scientist Office Cardiovascular and Pulmonary Imaging in SARS Coronavirus disease-19 (CISCO-19) study. Cardiovasc Res. 2020 Dec 1;116(14):2185-2196. doi: 10.1093/cvr/cvaa209.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- GN20ID164
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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