SARCODO: Coagulopathy and Vasculopathy Assessment as a Predictor of the Severity of SARS-CoV-2 / COVID-19 Infection

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Recruiting
CT.gov ID
NCT04624997
Collaborator
National Research Agency, France (Other)
1,000
Enrollment
2
Locations
17.8
Anticipated Duration (Months)
500
Patients Per Site
28.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

On 30 January 2020, WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern. Compared to SARS-CoV, which caused an outbreak of SARS in 2003, SARS-CoV-2 has a higher transmission capacity. Although the clinical manifestations of SARS-CoV-2 are dominated by respiratory symptoms, some patients have severe cardiovascular damage. In addition, patients with underlying cardiovascular disease may be at increased risk of death. Therefore, understanding the impairments caused by SARS-CoV-2 to the cardiovascular system and the underlying mechanisms is of the utmost importance.

Circulating endothelial cells (CECs) are generally considered markers of lesions and may be non-invasive markers of pulmonary vascular dysfunction during SARS-CoV-2 infection. Another marker of endothelial activation could be circulating extracellular vesicles. They could also be involved in the spread of the virus. Thus this project proposes to study different aspects of the diagnosis and pathophysiology of SARS-CoV-2. We propose to fully study activation state of coagulation and endothelium on a plasma and cellular side in patients diagnosed with SARS-CoV-2/COVID19. The different forms of the disease will be included: without lung disease, with a more or less severe lung disease, i.e. having evolved or not towards acute respiratory distress syndrome (ARDS). Extensive research of biomarkers will be compared to the detection of the virus in the respiratory tract as well as in the blood. This work will contribute to a better description of disease pathophysiology and should allow us to identify a patient profile in whom preventive or curative anticoagulant therapy could be considered.

Condition or DiseaseIntervention/TreatmentPhase
  • Other: biological sample

Detailed Description

In December 2019, an outbreak of pneumonia caused by a new coronavirus occurred in Wuhan and spread rapidly throughout China, with the evolution towards a global pandemic. Originally called new coronavirus 2019 (2019-nCoV), the virus was later officially named Coronavirus 2 of Severe Acute Respiratory Syndrome (SARS-CoV-2) by WHO. On 30 January 2020, WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern. Compared to SARS-CoV, which caused an outbreak of SARS in 2003, SARS-CoV-2 has a higher transmission capacity. Although the clinical manifestations of SARS-CoV-2 are dominated by respiratory symptoms, some patients have severe cardiovascular damage. In addition, patients with underlying cardiovascular disease may be at increased risk of death. Therefore, understanding the impairments caused by SARS-CoV-2 to the cardiovascular system and the underlying mechanisms is of the utmost importance. During this Chinese epidemic, a coagulopathy was found in severe cases of SARS-CoV-2 infection, including significantly higher levels of D-dimers in severe forms, disturbed PT and aPTT ratio compared to survivors (P <0.05). 71.4% of non-survivors and 0.6% of survivors met the criteria for disseminated intravascular clotting during their hospital stay. This study was confirmed in a second Chinese population where DDimers are still correlated with mortality. The hypothesis of microthrombosis at the renal level was also associated with activation of coagulation since high levels of creatinine were associated with higher levels of DDimers, in favor of a thrombotic origin for kidney failure. Endothelial dysfunction may thus have a major role in the respiratory physiopathologic process as well as in the viral dissemination processes. Indeed, the SARS-CoV-2 receptor (ACE2) is strongly expressed in endothelial cells. Infection of endothelial cells could cause a lesion of the endothelium but also an activation that can trigger the activation of coagulation. Circulating endothelial cells (CECs) are generally considered markers of lesions and may be non-invasive markers of pulmonary vascular dysfunction during SARS-CoV-2 infection. Another marker of endothelial activation could be circulating extracellular vesicles. They could also be involved in the spread of the virus. Thus this project proposes to study different aspects of the diagnosis and pathophysiology of SARS-CoV-2. We propose to fully study activation state of coagulation and endothelium on a plasma and cellular side in patients diagnosed with SARS-CoV-2/COVID19. The different forms of the disease will be included: without lung disease, with a more or less severe lung disease, i.e. having evolved or not towards acute respiratory distress syndrome (ARDS). Extensive research of biomarkers will be compared to the detection of the virus in the respiratory tract as well as in the blood. This work will contribute to a better description of disease pathophysiology and should allow us to identify a patient profile in whom preventive or curative anticoagulant therapy could be considered.

Study Design

Study Type:
Observational
Anticipated Enrollment :
1000 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Evaluation de la COagulopathie et de la Dysfonction enDOthéliale Comme Facteur prédictif de la gravité de l'Infection Par SARS-CoV-2 / COVID-19
Actual Study Start Date :
Jun 8, 2020
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Patient suspected COVID-19

Follow-up of patients as usual in care for infection. No specific puncture. Blood sample collect at admission and every 72h during hospitalisation for hemostasis evaluation, DNA extraction, Circulating endothelial cells measuring. Sampling can be delayed for 24h to match a planned blood collection for care or other research.

Other: biological sample
biological sample

Outcome Measures

Primary Outcome Measures

  1. Measure D-dimers (ng/ml) to study coagulopathy to characterize COVID-19 [28 days]

    Characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process

  2. Measure fibrin monomers (µg/ml) to study coagulopathy to characterize COVID-19 [28 days]

    Characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process

Secondary Outcome Measures

  1. Study troponin (ng/ml) to characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process [28 days]

  2. Study von Willebrand factor antigen (%) to characterize COVID-19 and identify patient populations who will develop or aggravate a micro or macro thrombotic process [28 days]

  3. Study association of genetical and constitutive factors of thrombophilia :blood type ABO and COVID-19 severity according to OMS classification [28 days]

  4. Study association of genetical and constitutive factors of thrombophilia: deficit in S protein and COVID-19 severity according to OMS classification [28 days]

  5. Study association of genetical and constitutive factors of thrombophilia:deficit in C protein and COVID-19 severity according to OMS classification [28 days]

  6. Study association of genetical and constitutive factors of thrombophilia: mutation in V factor of coagulation and COVID-19 severity according to OMS classification [28 days]

  7. Study association of genetical and constitutive factors of thrombophilia:mutation in II factor of coagulation and COVID-19 severity according to OMS classification [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients at least 18 years old

  • Hospitalized for suspected COVID-19 in the medical wards or intensive care unit.

  • Patients benefiting from a social security scheme

  • Patient who has been informed of the study

Exclusion Criteria:
  • Patients under guardianship / curatorship

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Hôpital CochinParisFrance75014
2Hôpital Européen Georges PompidouParisFrance75015

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris
  • National Research Agency, France

Investigators

  • Principal Investigator: David M Smadja, HEGP, AP-HP

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT04624997
Other Study ID Numbers:
  • APHP200521
  • 2020-A01048-31
First Posted:
Nov 12, 2020
Last Update Posted:
Oct 12, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Assistance Publique - Hôpitaux de Paris
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 12, 2021