NCT05125913

Brief Summary

The occurrence of novel coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has offered an unmatched global challenge for the healthcare research community. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme (ACE2), which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. Autopsy studies detected the presence of SARS-CoV-2 in both myocardium and renal tissue, suggesting that COVID-19 profoundly influences the cardiovascular (CV) system and the kidneys and this may lead to long-termed cardio-pulmonary-renal consequences. Data emerging from the general population suggests that COVID-19 is essentially an endothelial disease, with possible deleterious long-term effects that are currently incompletely understood. Therefore, the investigators aim to assess the CV risk in a chronic kidney disease (CKD) including dialysis patients and kidney transplanted (KTx) population, following SARS-CoV-2 infection, by determining the long-term impact of this disease on CV and renal outcomes in the aforementioned population as compared to a control group of matched patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jan 2021

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 4, 2021

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

November 10, 2021

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 18, 2021

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2024

Completed
Last Updated

January 21, 2022

Status Verified

January 1, 2022

Enrollment Period

3 years

First QC Date

November 10, 2021

Last Update Submit

January 5, 2022

Conditions

Outcome Measures

Primary Outcomes (5)

  • Mortality rate

    One of the primary outcome of this study will be all-cause mortality rate.

    24 months post-COVID-19

  • MACE

    Another primary outcome will be a composite CV outcome (time to first non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure or CV death).

    24 months post-COVID-19

  • Endothelial dysfunction

    The investigators will determine long-term impact of the COVID-19 on markers of CV risk and ED in all included patients.

    6 months post-COVID-19

  • Endothelial dysfunction

    The investigators will determine long-term impact of the COVID-19 on markers of CV risk and ED in all included patients.

    12 months post-COVID-19

  • Endothelial dysfunction

    The investigators will determine long-term impact of the COVID-19 on markers of CV risk and ED in all included patients.

    24 months post-COVID-19

Secondary Outcomes (3)

  • Renal outcome

    6 months post-COVID-19

  • Renal outcome

    12 months post-COVID-19

  • Renal outcome

    24 months post-COVID-19

Study Arms (2)

COVID-19 group

Patients with CKD stage 3-5, on dialysis or kidney transplanted patients with confirmed SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR), at minimum 2 weeks after the confirmed test.

Diagnostic Test: FMDDiagnostic Test: Arterial stiffnessDiagnostic Test: Assessment of IMTDiagnostic Test: EchocardiographyDiagnostic Test: LUSDiagnostic Test: BIS analysisOther: Biomarkers determination

non-COVID-19 group

CKD stage 3-5, dialysis or kidney transplantation matched patients without confirmed SARS-CoV-2 infection

Diagnostic Test: FMDDiagnostic Test: Arterial stiffnessDiagnostic Test: Assessment of IMTDiagnostic Test: EchocardiographyDiagnostic Test: LUSDiagnostic Test: BIS analysisOther: Biomarkers determination

Interventions

FMDDIAGNOSTIC_TEST

Measurements will be made by using ultrasound system with a 12-Mhz probe. All vasoactive medications will be withheld for 24 h before the procedure. The participants will remain at rest in the supine position for at least 15 minutes before the examination. Each subject's right arm will be comfortably immobilized in the extended position to allow consistent recording of the brachial artery 2-4 cm above the antecubital fossa. If an arteriovenous fistula is present, the contralateral arm will be used for assessment. Three adjacent measurements of end-diastolic brachial artery diameter will be made from single 2D frames. The maximum FMD diameters will be calculated as the average of the three consecutive maximum diameter measurements after hyperemia and nitroglycerin, respectively.

COVID-19 groupnon-COVID-19 group
Arterial stiffnessDIAGNOSTIC_TEST

Arterial stiffness assessment will be performed by applanation tonometry with the patient being recumbent, 10 minutes before the measures were done. The carotid and femoral pulse will be acquired by applanation tonometry sequentially, allowing a single operator to acquire the measurement. The transit time from the R-wave of the simultaneously acquired electrocardiogram to the foot of the carotid and femoral pulse is measured. The difference-acquired electrocardiogram to the foot of the carotid and femoral pulse is measured. The difference between these 2 transit times is divided by distances measured from the body surface to estimate the arterial path length in order to calculate carotid-femoral PWV.

COVID-19 groupnon-COVID-19 group
Assessment of IMTDIAGNOSTIC_TEST

A high-resolution B-mode ultrasound of the common carotid arteries with scanning of the longitudinal axis until the bifurcation and of the transversal axis will be performed using ultrasonic pulse with a middle frequency of 12 MHz. For each carotid artery, two longitudinal measurements will be obtained by rotating the vessels at 180o increments along their axis. IMT will be measured at 1 cm proximal to the bifurcation on each side.

COVID-19 groupnon-COVID-19 group
EchocardiographyDIAGNOSTIC_TEST

Echocardiography will be performed on each patient at baseline; the measurements will be carried out according to the recommendations of the American Society of Echocardiography by an observer unaware of the lung ultrasound and bioimpedance results. Echocardiographic evaluation will provide information about cardiac anatomy (e.g. volumes, geometry, mass) and function (e.g. left ventricular function and wall motion, valvular function, right ventricular function, pulmonary artery pressure, pericardium).

COVID-19 groupnon-COVID-19 group
LUSDIAGNOSTIC_TEST

Examinations will be performed in the supine position. Scanning of the anterior and lateral chest will be performed on both sides of the chest, from the second to the fourth (on the right side to the fifth) intercostal spaces, at parasternal to mid-axillary lines. B-lines will be recorded in each intercostal space and were defined as a hyperechoic, coherent US bundle at narrow basis going from the transducer to the limit of the screen. B-lines starting from the pleural line can be either localized or scattered to the whole lung and be present as isolated or multiple artifacts. The sum of B-lines produces a score reflecting the extent of lung water accumulation (0 being no detectable B-line).

COVID-19 groupnon-COVID-19 group
BIS analysisDIAGNOSTIC_TEST

This analysis will be performed at baseline using the portable whole-body multifrequency bioimpedance analysis device using specific electrodes. Based on a fluid model using 50 discrete frequencies (5-1000kHz), the extracellular water (ECW), the intracellular water (ICW) and the total body water (TBW) are calculated. These volumes are then used to determine the amount of fluid overload. All calculations are automatically performed by the software of the BCM® device. Absolute fluid overload (AFO) is defined as the difference between the expected patient's ECW under normal physiological conditions and the actual ECW, whereas the relative fluid overload (RFO) is defined as the absolute fluid overload AFO to ECW ratio.

COVID-19 groupnon-COVID-19 group

Biomarkers by ELISA: IL-1, IL-6, VCAM1, Endoglin, NO and ADMA

COVID-19 groupnon-COVID-19 group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

This prospective case-control study will include CKD stage 3 to 5 patients, dialysis patients and KTx patients.

You may qualify if:

  • Age\>18 years;
  • Patients with CKD stage 3-5, patients on dialysis or KTx patients with confirmed COVID-19, at minimum 2 weeks after the confirmed test;
  • Age, sex and kidney disease (CKD stage 3-5, dialysis or KTx) matched patients without confirmed SARS-CoV-2 infection.

You may not qualify if:

  • Prior diagnosis of pulmonary fibrosis, pneumectomy or massive pleural effusion;
  • Active malignancies.
  • Pregnancy;
  • Active systemic infections (due to difficulties in the interpretation of nonspecific inflammation biomarkers in this type of patients);
  • Congenital heart disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dr CI Parhon Clinical Hospital of Iasi

Iași, Romania

RECRUITING

Related Publications (1)

  • Tapoi L, Apetrii M, Dodi G, Nistor I, Voroneanu L, Siriteanu L, Onofriescu M, Kanbay M, Covic A. Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial. BMC Nephrol. 2022 May 6;23(1):176. doi: 10.1186/s12882-022-02809-4.

Biospecimen

Retention: SAMPLES WITH DNA

Serum samples

MeSH Terms

Conditions

COVID-19Cardiovascular Diseases

Interventions

Vascular StiffnessEchocardiography

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cardiovascular Physiological PhenomenaCirculatory and Respiratory Physiological PhenomenaCardiac Imaging TechniquesDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisUltrasonographyHeart Function TestsDiagnostic Techniques, Cardiovascular

Study Officials

  • Adrian C Covic, Professor

    Grigore T. Popa University of Medicine and Pharmacy

    STUDY DIRECTOR

Central Study Contacts

Mugurel Apetrii, Lecturer

CONTACT

Gianina Dodi, Researcher

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 10, 2021

First Posted

November 18, 2021

Study Start

January 4, 2021

Primary Completion

December 31, 2023

Study Completion

March 31, 2024

Last Updated

January 21, 2022

Record last verified: 2022-01

Locations