Clinical trial NCT04609332: Endothelial Damage and Angiogenesis Biomarkers During COVID-19
Official title: Association of Endothelial Damage and Angiogenesis Biomarkers With Morbidity and Mortality in SARS-CoV-2 Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Angiogenesis
Endothelial Dysfunction
Cardiovascular Morbidity
Keywords: Syndecan-1
Thrombomodulin
VEFG
ANG-2
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2020-10-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The investigators will include Covid 19 patients admitted to ICU with the need for oxygen and ventilatory support. Blood plasma biomarkers will be obtained on the first and 10th day of hospitalization. Information on major cardiac events will be obtained from the patient clinical file and by phone interview after hospitalization.

Brief summary: Severe SARS-CoV-2 disease is characterized by a progressive hypoxemic respiratory failure. Autopsies from these patients show severe endothelial damage with extensive vascular thrombosis, microangiopathy, and occlusion of alveolar capillaries and, finally, evidence of new vessel growth through intussusceptive angiogenesis.

This research aims to study endothelial damage and angiogenesis biomarkers and its association with major cardiovascular events.

Detailed description: To study the presence of endothelial damage and angiogenic biomarkers with major cardiovascular events, the investigators will perform an observational study to evaluate plasma biomarkers concentrations in Covid-19 patients hospitalized in critical care units.

After ethical review board approval, the investigators will select 40 patients admitted to intensive care units (ICU). After patient written consent or if the participants are unable to consent, after a relative subrogated acceptance, the investigators will collect blood samples in the first 24 hrs and on the 10th day of hospitalization.

Venous blood samples are collected. After obtaining all samples, serum Syndecan-1, thrombomodulin, ANG-2, FGF basic, HGF, IL-8, PDGF-BB, TIMP-1, TIMP-2, TNFα y VEGF will be determined by a researcher blinded to the patient using commercially available Elisa kits. The concentration of each biomarker at each sample time will be compared. The investigators will observe clinical outcomes after one, 3, 6, and 12 months after the hospitalization.

The investigators found no previous data of this measurement in the COVID-19 scenario. In this observational study, the investigators select a sample size on convenience for the primary outcome.

Eligibility criteria: Inclusion Criteria:

1. Patients older than 18 years
2. Patient with a diagnosis of COVID-19 confirmed by PCR
3. Patient with radiological image suggestive of COVID-19 with pending confirmation
4. Need for ventilatory support with oxygen therapy by HFNC (High-flow nasal cannula)
5. Need for invasive mechanical ventilation.

Exclusion Criteria:

1. Patient with an image suggestive of COVID-19 with negative PCR
2. Anticoagulation users before admission for any reason.

Primary outcomes:
measure: Change from Baseline Syndecan-1 concentration at 10th day
timeFrame: 24 Hours, 10 Days
Secondary outcomes:
measure: Change from Baseline ANG-2 concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline FGF basic concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline HGF concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline IL-8 concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline PDGF-BB concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline TIMP-1 concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline TIMP-2 concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline TNFα concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline VEGF concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Change from Baseline Thrombomodulin concentration at 10th day
timeFrame: 24 Hours, 10 Days
measure: Major cardiovascular events
timeFrame: 1 month, 3 months, 6 months 12 months.
Other outcomes:
Locations:
city: Independencia
country: Chile
facility: Hospital Clínico de la Universidad de Chile
state: Santiago
Study officials:
affiliation: Hospital Clínico de la Universidad de Chile
name: Felipe Maldonado, M.D., M.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maldonado F, Morales D, Diaz-Papapietro C, Valdes C, Fernandez C, Valls N, Lazo M, Espinoza C, Gonzalez R, Gutierrez R, Jara A, Romero C, Cerda O, Caceres M. Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support. Front Med (Lausanne). 2022 Mar 16;9:826218. doi: 10.3389/fmed.2022.826218. eCollection 2022.