Cardiac Imaging in SARS-CoV-2 (COVID-19)

COVID Clinical Trial

— CISCO-19  

Official title:

Cardiovascular and Pulmonary Imaging in SARS-CoV-2: A Study of the Heart, Lungs and Wellbeing After COVID-19.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04403607
• Other study ID #: GN20ID164
• Status: Enrolling by invitation
• Start date: May 22, 2020
• Est. completion date: May 2023

Study information

• Verified date: March 2022
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

One-in-four patients with COVID-19 pneumonia develop life-threatening heart problems. Through cardiovascular imaging and biomarkers analyses this study aims to evaluate whether COVID-19 infection results in heart injury. The investigators will also investigate which patients are at risk of heart injury as a result of COVID-19 and why only some patients suffer heart problems as a consequence of the infection. The study will also assess multisystem involvement including the lungs and kidneys.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 180
• Est. completion date: May 2023
• Est. primary completion date: March 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Royal Infirmary	Glasgow
United Kingdom	Royal Alexandra Hospital	Paisley	Renfrewshire

Sponsors (2)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde	University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö 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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. Erratum in: Circulation. 2018 Nov 13;138(20):e652. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cardiovascular science - vascular biology	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.	1 year
Other	Cardiovascular science - mathematical modelling	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.	1 year
Other	Cardiovascular science - pathology	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.	1 year
Other	Health outcomes (serious adverse events)	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.	20 years
Primary	The primary cardiac outcome is the proportion of patients with a diagnosis of myocardial inflammation (myocarditis).	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.	28 days after discharge from hospital
Primary	The primary cardio-pulmonary outcome is the proportion of patients with thrombosis	Thrombosis of the right heart, pulmonary arteries and left heart will be determined contrast-enhanced CT chest, angiography and MRI.	28 days after discharge from hospital
Secondary	Myocardial injury	Assess mechanisms using circulating biomarkers of cardiac injury, high sensitivity troponin I (ng/L) and its change over time from baseline.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Myocardial stress	Assess the significance of myocardial injury by measuring circulating concentrations of NTproBNP (pg/mL) and its change over time from baseline.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Systemic inflammation	Assess systemic inflammation by measurement of the peak circulating concentration of C-reactive protein (mg/dL) and its change over time.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Vascular injury	Assess vascular injury/inflammation by measurement of the peak circulating concentration of IL-6 (pg/mL) and its change over time.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Endothelial activation and haemostasis	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.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Fibrin lysis	Assess fibrin lysis by measurement of the peak circulating concentration of fibrin D-dimer (IU/dL) and its change over time.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Coagulation	Assess coagulation by measurement of Activated Partial Thromboplastin Time (APTT) in seconds. Other measures of coagulation will also be measured.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Platelet count	Assess platelet count (n/microlitre), minimum value (thrombocytopaenia) and change over time.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Renal function	Assess renal function using urine albumin:creatinine ratio and its change over time. Other measures of renal function/injury will also be assessed.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Quantify myocardial perfusion as a measure of coronary microvascular function	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.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Association of the primary outcome according to a prior history of cardiovascular disease or no history of prior cardiovascular disease.	Imaging for coronary disease, PTE and lung pathology will be correlated with NHS clinical data on prior history of cardiovascular disease.	28 days after discharge from hospital, > 1 year post discharge (average 18-22 months)
Secondary	Patient reported outcome measures (PROMS) - health status	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.	1 year
Secondary	PROMS - functional capacity	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)	1 year

External Links

•   Chief Scientist Office, Scottish Government - Rapid Research in Covid-19 (RARC-19)
•   Glasgow Clinical Trials Unit