Glycaemia and Cardiac Function in Patients With COVID-19

Study Overview
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Brief Summary
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The study design is observational, exploratory study consisting of two cohorts of COVID-19 patients admitted to the ICU and the medical ward, respectively. The primary outcome focusing on the effect of plasma glucose levels on cardiac function will be evaluated by repeated assessment of cardiac function by echocardiography and measurement of plasma glucose. Furthermore, blood coagulability will be evaluated to determine the importance of diabetes status and plasma glucose changes for whole blood coagulability at time of admission to the ICU and progression in coagulability abnormalities. In the medical ward cohort, two assessments will be performed separated by no more than 12 hours. In the ICU cohort, three assessments will be performed separated by no more than 6 hours. Ideally, 60 patients with COVID-19 will be included in the ICU cohort with a 1:1 distribution between patient with and without diabetes. Ideally, 40 patients with diabetes will be included in the cohort of patients admitted to medical ward (hospitalisation cohort). The primary hypothesis is that levels of plasma glucose have clinically significant impact on left ventricular systolic function in patients with COVID-19 admitted to the ICU. The secondary hypothesis is that the impact of plasma glucose on left ventricular systolic function is associated with glycaemic control prior to admission as measured by HbA1c.

Official Title
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Glycaemia and Cardiac Function in Patients With COVID-19

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1, COVID

Intervention / Treatment
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* Other: Glycaemic levels


Participation Criteria
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Eligibility Criteria
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The ICU cohort - Inclusion criteria Informed and written consent Age ≥18 years Verified COVID-19 Admission to the ICU within the last 24 hours Type 1 or type 2 diabetes prior to admission (the diabetes sub-group only) The ICU cohort - Exclusion criteria Cardiac arrhythmia at time of inclusion (previously diagnosed paroxysmal atrial fibrillation will be allowed) Pacemaker rhythm Severe valve disease The hospitalisation cohort - inclusion criteria Informed and written consent Age ≥18 years Verified COVID-19 Admission to medical ward within the last 24 hours Type 1 or type 2 diabetes prior to admission The hospitalisation cohort - Exclusion criteria Cardiac arrhythmia at time of inclusion (previously diagnosed paroxysmal atrial fibrillation will be allowed) Pacemaker rhythm Severe valve disease Withdrawal criteria - The participants may withdraw at will at any time

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The intensive care unit cohort<br>Patients (with or without diabetes) with COVID-19 admitted to the intensive care unit | Other: Glycaemic levels<br>* Glycaemic levels during admission for COVID-19<br>|
| The hospitalisation cohort<br>Patients with diabetes and COVID-19 admitted to the medical ward | Other: Glycaemic levels<br>* Glycaemic levels during admission for COVID-19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose levels and left ventricular ejection fraction | The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction (a pooled analysis of the hospitalisation cohort and ICU cohort) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary outcome: HbA1c, plasma glucose levels and left ventricular systolic function | Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Plasma glucose levels and strain analysis | The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis (a pooled analysis of the hospitalisation cohort and ICU cohort) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Plasma glucose levels and mitral annular systolic velocity | The within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity (a pooled analysis of the hospitalisation cohort and ICU cohort) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Plasma glucose levels and left ventricular ejection fraction (sub-group analysis) | Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by left ventricular ejection fraction between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Plasma glucose levels and strain analysis (sub-group analysis) | Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Plasma glucose levels and mitral annular systolic velocity (sub-group analysis) | Differences in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity between the hospitalisation cohort, the ICU cohort with diabetes and the ICU cohort without diabetes, respectively | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| HbA1c, Plasma glucose levels and strain analysis | Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by strain analysis between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| HbA1c, Plasma glucose levels and mitral annular systolic velocity | Difference in the within-subject effect of plasma glucose levels on left ventricular systolic function as measured by mitral annular systolic velocity between patients with chronic hyperglycaemia prior to admission (HbA1c >53 mmol/mol) and with normoglycaemia prior to admission (HbA1c ≤53 mmol/l) (ICU cohort only) | The study applies a mixed model for assessment of within-subject effects by repeated assessment in same individual. The time frame is from first assessment until last assessment (max. 24 hours). | 
| Diabetes status and whole blood coagulability and fibrinolysis | Difference in whole blood coagulability and fibrinolysis as measured by TEG between patients with and without diabetes at time of admission to the ICU (ICU cohort only) | At time of admission to the ICU (max. 24 hours after admission to the ICU) | 
| Diabetes status and change in whole blood coagulability and fibrinolysis during ICU stay | Difference in change in whole blood coagulability and fibrinolysis as measured by TEG between patients with and without diabetes treated at the ICU (ICU cohort only) | From first until last assessment during ICU stay (max. 24 hours). | 
| Prognostic value of TEG analysis | The prognostic value of cardiac function and TEG on the following patient outcomes 1) need for treatment in the ICU (hospitalisation cohort only) 2) need for respirator treatment (hospitalisation cohort only) 3) COVID-19 related death | From time of admission and until four weeks after admission | 
| Prognostic value of cardiac function | The prognostic value of cardiac function on the following patient outcomes 1) need for treatment in the ICU (hospitalisation cohort only) 2) need for respirator treatment (hospitalisation cohort only) 3) COVID-19 related death | From time of admission and until four weeks after admission | 
| Diabetes status and high-sensitivity troponins | Difference in cardiac damage as measured by high-sensitivity troponin (hs-troponin) between patients with and without diabetes admitted to the ICU (ICU cohort only) | At the time of admission to the ICU (max. 24 hours after admission to the ICU) | 
| Diabetes status and change high-sensitivity troponins | Difference in change in cardiac damage as measured by high-sensitivity troponin (hs-troponin) between patients with and without diabetes admitted to the ICU (ICU cohort only) | From first until last assessment during ICU stay (max. 24 hours) |