Clinical trial NCT05608603: Diagnostics of Coronavirus Disease 2019 Cardiovascular Complications
Official title: Observational Cohort Prospective Study of Diagnostics of Coronavirus Disease 2019 Cardiovascular Complications Using Remote Electrocardiogram Monitoring and Pulse Wave
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: COVID-19
Endothelial Function
Diastolic Dysfunction
Oxygen Consumption
Quality of Life
Exercise Tolerance
Keywords: COVID-19
markers of endothelial function
diastolic dysfunction
oxygen consumption
flow mediated dilatation
proton mass spectrometry
remote ECG monitoring
pulse vawe
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2022-11-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population consist all men and women from 18 to 80 age in a community according inclusion, non-inclusion, exclusion criteria

Brief summary: Aim of this prospective, observational, multi-centered, randomized study is to detect cardiovascular complications in patients after coronavirus infection.

The study will include 100 patients who underwent confirmed by laboratory tests COVID-19 infection (polymerase chain reaction (PCR) testing, enzyme-linked immunosorbent assay (positive result at least 1 time)) 1-3 months ago with the degree of lung lesion more than 25%, who were admitted to the University Clinical Hospital No. 4 of I.M. Sechenov First Moscow State Medical University.

The study consists of 4 periods:

1. Screening for up to 6 months.
2. Inclusion in the study, undergoing of identical laboratory and instrumental testing.
3. Re-examination of patients. After 6 months from the initial examination (9 months after discharge from the infectious diseases department), patients will be re-examined.

4 Determination of end points, statistical data processing.

Estimated result of the study is to confirm or refute the hypothesis:

1. As a result of the analysis of ECG and pulse wave data and comparison with echocardiography data, identify cardiovascular complications of COVID-19 infection.
2. To determine the diagnostic significance of pulse wave parameters for assessing cardiovascular complications in patients with a history of COVID-19 infection (sensitivity, specificity, positive and negative predictive value).
3. Identify correlations between pulse wave parameters and biochemical markers of endothelial dysfunction (endothelin-1).
4. As a result of the analysis of exhaled air by the proton mass spectrometry, to identify markers of cardiovascular complications in patients after COVID-19 infection.
5. As a result of a cardiorespiratory stress test, determine the respiratory and cardiovascular causes of dyspnea, exercise tolerance of patients after infection with COVID-19.

Detailed description: Aim of this prospective, observational, multi-centered, randomized study is to detect cardiovascular complications in patients after coronavirus infection.

The study will include 100 patients who underwent confirmed by laboratory tests Coronavirus Disease 2019 (COVID-19) infection (polymerase chain reaction (PCR) testing, enzyme-linked immunosorbent assay (positive result at least 1 time)) 1-3 months ago with the degree of lung lesion more than 25%, who were admitted to the University Clinical Hospital No. 4 of I.M. Sechenov First Moscow State Medical University.

The study consists of 4 periods:

1. Screening for up to 6 months. Performed by a pulmonologist. Patients meeting the inclusion criteria are selected.
2. Inclusion in the study. If the patient meets the inclusion criteria, a discussion about the nature of the study is held with the patient. Further, consent to participate in the study and to process personal data is obtained. After, the epicrisis from the COVID-19 infectious diseases department is analyzed.

   Patients are provided with medical care in accordance with the standards approved by the Ministry of Health of the Russian Federation, and local acts of the institution in which the study is carried out.

   Patients eligible for inclusion will undergo the following investigations:
   * Anamnesis and complaints collection; physical examination;
   * Assessment of the quality of life and psycho-emotional status using the Short Form-36 (SF36) and Hospital Anxiety and Depression Scale (HADS) questionnaires, as well as the six-minute walk test;
   * General and biochemical blood tests , urine analysis, , determination of biochemical markers of endothelial dysfunction (endothelin-1) in the blood;
   * Electrocardiography, a flow mediated dilatation procedure for endothelial function assessment, transthoracic echocardiography to identify the structural and functional features of the myocardium, spiroergometry to determine the patient's oxygen consumption.
   * Electrocardiogram (ECG) in one lead with an assessment of the pulse wave using a portable cardiac monitor "CardioQvark"
   * The analysis of exhaled air will be performed using the Compact proton mass spectrometer (PTR-MS) manufactured by Ionicon (Austria).
3. Re-examination of patients. After 6 months from the initial examination (9 months after discharge from the infectious diseases department), patients will be re-examined, In the interval between the initial and repeated examinations, the condition of all patients will be monitored, for this it is expected to make phone calls, the frequency of 1 time per month.

4 Determination of end points, statistical data processing. The statistical processing will be performed using the Python Software Foundation version 3.8 for Windows (Delaware, USA).

Estimated result of the study is to confirm or refute the hypothesis:

1. As a result of the analysis of ECG and pulse wave data and comparison with echocardiography data, identify cardiovascular complications of COVID-19 infection.
2. To determine the diagnostic significance of pulse wave parameters for assessing cardiovascular complications in patients with a history of COVID-19 infection (sensitivity, specificity, positive and negative predictive value).
3. Identify correlations between pulse wave parameters and biochemical markers of endothelial dysfunction (endothelin-1).
4. As a result of the analysis of exhaled air by the proton mass spectrometry, to identify markers of cardiovascular complications in patients after COVID-19 infection.
5. As a result of a cardiorespiratory stress test, determine the respiratory and cardiovascular causes of dyspnea, exercise tolerance of patients after infection with COVID-19.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent to participate in the study;
2. Age 18 and over;
3. Male and female;
4. COVID-19 infection confirmed by laboratory tests (polymerase chain reaction testing, enzyme-linked immunosorbent assay (positive result at least 1 time) with a CT degree more that 25% of lung lesion.
5. No more than 3 months after discharge from infectious department

Non-inclusion criteria:

1. Unable to sign informed consent;
2. Mental illness (severe dementia, schizophrenia, severe depression, manic-depressive psychosis);
3. Acute coronary syndrome, acute cerebrovascular accident, pulmonary embolism within the last 3 months;
4. Oncology;
5. Diseases and conditions that can change the ECG picture and complicate the analysis of the ECG (conduction disturbance, pacemaker);
6. Inability to use a heart monitor (congenital developmental anomalies, traumatic amputation of the upper limbs, essential tremor, Parkinson's disease);
7. Severe comorbidities with life expectancy less than 1 year.

Exclusion Criteria:

1. Refusal to further participation in the study;
2. Acute infectious diseases, tuberculosis
3. Oncology arising in the process of the study
4. Acute coronary syndrome, acute cerebrovascular accident, pulmonary embolism arising in the process of the study
5. Acute psychotic reactions arising in the process of the study;
6. Inability to use a heart monitor arising in the process of the study

Primary outcomes:
measure: Changes in endothelin-1 in dynamics (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in the diastolic function of the right and left ventricles (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Change in ejection fraction (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in the volumes of the heart cavities (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Change in speed indicators on the heart valves (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Change in mean and diastolic pressure of the pulmonary artery (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in the cardio-ankle vascular index and ankle-brachial index (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in the spectrum of volatile organic compounds in exhaled air in patients after COVID-19 infection over time (compared with initial indicators)
timeFrame: In 9 months after the recovery from COVID-19
measure: Change in oxygen pulse (VO2/HR) at the peak of the load
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in ventilation parameters (tidal volume (Vt), minute ventilation (VE), Vt/FVC index (ratio of tidal volume to forced vital capacity), respiratory reserve (BR)) over time
timeFrame: In 9 months after the recovery from COVID-19
measure: Changes in gas exchange parameters (end-expiratory partial pressure of exhaled carbon dioxide (PetCO2), ventilation equivalent for carbon dioxide (VE/VCO2), ventilation-perfusion ratio (Vd/Vt)) in dynamics
timeFrame: In 9 months after the recovery from COVID-19
Secondary outcomes:
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University (Sechenov University)ogy, Center "Digital biodesign and personalized healthcare")
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Philippe Yu Kopylov, Professor
role: STUDY_DIRECTOR
References: