Clinical trial NCT04438993: The COVID-19 Disease and CARdiac Events Study
Official title: An Observational Study of Hospitalised Patients With Coronavirus Disease 2019 (COVID-19) to Determine the Degree of Myocardial Injury Using Biomarkers and Echocardiography, and the Impact of This on Cardiovascular Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID
Coronavirus
Keywords: Echocardiogram
Troponin
NT-proBNP
Cytokines
Lead sponsor: NHS Lanarkshire
Sponsor class: OTHER_GOV
First posted: 2020-06-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We plan to enrol all consecutive admissions with COVID-19 disease admitted to UHH up until a maximal target of 100 patients have been recruited. Patients will have a positive real time reverse transcription (rt)PCR for SARS-CoV-2 nasopharyngeal swab and/or chest X-ray or CT imaging showing classical COVID-19 disease abnormalities ('classic/probable COVID-19, mild/mod or severe' according to current British Society of Thoracic Imaging guidance, and be within 5 days of admission (so as to enable us to retrospectively add on biomarkers to blood samples sent on admission to hospital).

Brief summary: An observational study of consecutive patients testing positive for COVID-19 who require admission to hospital to determine the degree of myocardial injury through biomarkers and echocardiography and the impact of this on cardiovascular outcomes. The COVID-19 disease and CARdiac Events study (COVICARE).

Detailed description: Purposes:

1. To determine the prevalence of myocardial injury/impairment in patients hospitalised with COVID-19 disease.
2. To determine the predictive value of baseline biomarkers in identifying patients at high risk of significant morbidity/mortality due to COVID-19.

Justification:

The Novel Coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first recorded in Hubei Province of Wuhan China in December 2019 has now swept the globe and has been declared a pandemic by the World Health Organisation.

The largest published registry from the Chinese centre for disease control and prevention (CDC) describes a disease with a broad range of acuity but found from a cohort of 72314 confirmed or suspected cases (72314) 14% of those affected required hospitalisation and 5% required critical care. Thus far treatment has focused on quarantine and supportive care.

Predicting outcomes in COVID disease requires risk stratifying infected patients. Data so far have mainly come from small studies in China but the consistent risk factors appear to be advanced age, diabetes, hypertension and cardiovascular disease. The CDC report a 10.5% risk of death associated with underlying cardiovascular disease, surprisingly more than those with respiratory disease, especially given that lung involvement is the dominant clinical presentation. The reason for poor outcome in cardiovascular disease is unknown but is likely to be multifactorial. A literature search of nine observational studies reported myocardial injury based on high sensitivity troponin, abnormal ECG, abnormal echocardiogram or a combination of the three. The reported rate of myocardial injury ranged from 7-28% and in all groups was associated with higher rates of requirement for critical care. Mortality was increased compared to those without myocardial injury- 51.2% vs 4.5%.

Trial overview:

Patients admitted to University Hospital Hairmyres (UHH) with confirmed COVID-19 will have 3 biomarkers - high sensitivity troponin T (hsTnT), N-terminal (NT)-proBNP and ferritin - added on retrospectively to their admission blood samples, and an additional sample will be taken for cytokine analysis.

An ECG and echocardiogram will be performed.

Patients will be observed during the remainder of the hospitalisation and for up to 30 days from admission for major adverse cardiac events.

Statistical analysis:

The prevalence of echocardiographic abnormalities in the cohort will be presented.

Biomarker levels will be compared between patients who require intensive treatment unit (ITU) admission or not, ventilation or not or who die or survive up to 30 days using independent samples t-tests if the data are normally distributed or Mann-Whitney-U tests if non normally distributed.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. In-patient in UHH within first 5 days of admission
3. COVID-19 disease confirmed on rtPCR detection of SARS-CoV-2 from nasopharyngeal swabs and/or thoracic X-ray imaging findings characteristic of COVID-19 disease (positive swab results preferred).
4. Able to provide written, informed consent.

Exclusion Criteria:

1. Refusal of consent for enrolment.
2. Known pre-existing left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) \<40%.

Primary outcomes:
measure: Cardiac abnormalities in COVID-19 disease in-patients
timeFrame: 6 months
Secondary outcomes:
measure: Biomarker - hsTnT
timeFrame: 30 days
measure: Biomarker - NT-proBNP
timeFrame: 30 days
measure: Biomarker - ferritin
timeFrame: 30 days
measure: Biomarker - cytokines
timeFrame: 30 days
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: University Hospital Hairmyres
state: Scotland
Study officials:
affiliation: NHS Lanarkshire
name: Robin A Weir, MD
role: PRINCIPAL_INVESTIGATOR
References: