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Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2 (COVID-19) (REACOVIM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04365166
Recruitment Status : Recruiting
First Posted : April 28, 2020
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
Direction Centrale du Service de Santé des Armées

Brief Summary:

The SARS-CoV2 virus causes severe or even fatal disease in a fraction of infected people. The clinical severity is based on a complicated pneumopathy with acute respiratory distress syndrome that can lead to multi-visceral failure. The underlying mechanism is a cytokinergic storm, an emerging facet of immunological dysregulation.

This clinical trial is aimed to understand the mechanisms of this immunological dysregulation in order to identify therapeutic levers.

The main objective is to understand the relationships between clinical severity, death or morbidity of resuscitation management, and immune status (i.e., immune pathways activated or not). Immune status will be investigated at many levels of organization (i.e., circulating leukocytes, cytokines and chemokines, transcripts).

The secondary objectives are :

  • to understand what is responsible for clinical severity, viral load, or immune activation;
  • to highlight the consequences of immunological dysregulation on associated risks (i.e., immunosuppression leading to the emergence of infectious comorbidities) as well as the functioning of neurotransmission through metabolic pathway diversions. The impact of dysimmunity on these biological pathways will be assessed with a metabolomic analysis;
  • to understand the mechanisms of vulnerability related to the field. Moreover, while co-morbidities are likely to be a risk factor for severe disease progression, there are many situations in which they do not occur. Stress, with its neurovegetative and endocrinological dimensions, modulates the immune response. It is essential to know whether the stress response plays a role in immunological dysregulation. This analysis is a prerequisite for understanding the conditions of treatment with glucocorticoids.

Angiotensin converting enzyme type 2 (ACE2) also plays a likely role in host viral infection. It is also thought to play an important role in the emergence of severe syndromes by affecting the quality of vascular response.


Condition or disease
Respiratory Tract Infections Respiratory Tract Disease

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Study of Clinical and Immune Severity Profiles of Patients Infected With SARS-Cov2
Actual Study Start Date : April 21, 2020
Estimated Primary Completion Date : April 21, 2022
Estimated Study Completion Date : April 21, 2022



Primary Outcome Measures :
  1. Mortality [ Time Frame: 90 days following the enrollment ]
    Mortality

  2. Immune response - Plasma cytokine profile [ Time Frame: Through study completion (90 days following the enrollment) ]
    Th1/Th2/Th17/Treg balance, Type I Interferons and inflammation

  3. Immune response - Phenotype of circulating cells [ Time Frame: Through study completion (90 days following the enrollment) ]
    T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)


Secondary Outcome Measures :
  1. Severity criteria - Duration of stay in intensive care unit [ Time Frame: 90 days following the enrollment ]
    Number of days in intensive care unit

  2. Severity criteria - Duration of hospitalization stay [ Time Frame: 90 days following the enrollment ]
    Number of days of hospitalization

  3. Severity criteria - Duration of period out of hospital [ Time Frame: 90 days following the enrollment ]
    Number of days out of hospital

  4. Severity criteria - Duration without mechanical ventilation [ Time Frame: 90 days following the enrollment ]
    Number of days without mechanical ventilation (invasive/non-invasive)

  5. Severity criteria - Duration without ventilation [ Time Frame: 90 days following the enrollment ]
    Number of days not being ventilated

  6. Severity criteria - Duration without intubation [ Time Frame: 90 days following the enrollment ]
    Number of days not being intubated

  7. Severity criteria - Number of transfusions [ Time Frame: 90 days following the enrollment ]
    Number of transfusions

  8. Severity criteria - Duration of the period without cathecholamines [ Time Frame: 90 days following the enrollment ]
    Number of days without cathecholamines

  9. Severity criteria - Duration of the period without dialysis [ Time Frame: 90 days following the enrollment ]
    Number of days without dialysis

  10. Severity criteria - SOFA [ Time Frame: Through study completion (90 days following the enrollment) ]
    Sepsis-related Organ Failure Assessment (SOFA) Score

  11. Severity criteria - LIS [ Time Frame: Through study completion (90 days following the enrollment) ]
    Lung Injury Score (LIS)

  12. SARS-Cov2 viral load [ Time Frame: Through study completion (90 days following the enrollment) ]
    SARS-Cov2 viral load will be measured in blood and in broncho-tracheal secretions

  13. Emergence of concomitant infections [ Time Frame: 90 days following the enrollment ]
    Co-infections and acquired infections (bacterial or fungal) in intensive care unit, in particular based on an all-site positive PCR for EBV and/or CMV and/or HSV

  14. Emergence of concomitant infections - Phenotype of circulating cells [ Time Frame: Through study completion (90 days following the enrollment) ]
    T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)

  15. Stress physiological profile - Sympathetic tone [ Time Frame: Through study completion (90 days following the enrollment) ]
    Heart rate variability

  16. Stress physiological profile - Temperature [ Time Frame: Through study completion (90 days following the enrollment) ]
    Core temperature

  17. Stress physiological profile - Glucocorticoids [ Time Frame: Through study completion (90 days following the enrollment) ]
    Quantity of glucocorticoids in the urine during 24 hours and at night

  18. Angiotensin converting enzyme type II (ACE2) polymorphism - ACE [ Time Frame: At enrollment ]
    ACE Polymorphism

  19. Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1 [ Time Frame: At enrollment ]
    Protein expression of ACE2 vs. ACE1 and angiotensin II chain proteins

  20. Comorbidities - diabetes [ Time Frame: At enrollment ]
    Diabete diagnosis

  21. Comorbidities - Heart disease [ Time Frame: At enrollment ]
    Heart disease diagnosis

  22. Comorbidities - organ failure [ Time Frame: At enrollment ]
    Organ failure diagnosis

  23. Plasma concentrations of several metabolic pathways - GABA [ Time Frame: Through study completion (90 days following the enrollment) ]
    GABA level in blood and urine

  24. Plasma concentrations of several metabolic pathways - Glucocorticoid [ Time Frame: Through study completion (90 days following the enrollment) ]
    Glucocorticoid level in blood and urine

  25. Plasma concentrations of several metabolic pathways - Tryptophan [ Time Frame: Through study completion (90 days following the enrollment) ]
    Tryptophan in blood and urine

  26. Plasma concentrations of several metabolic pathways - Serotonin [ Time Frame: Through study completion (90 days following the enrollment) ]
    Serotonin level in blood and urine

  27. Plasma concentrations of several metabolic pathways - Dopamin [ Time Frame: Through study completion (90 days following the enrollment) ]
    Dopamin level in blood and urine

  28. Plasma concentrations of several metabolic pathways - Cathecholamines [ Time Frame: Through study completion (90 days following the enrollment) ]
    Catecholamines level in blood and urine

  29. Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives [ Time Frame: Through study completion (90 days following the enrollment) ]
    Arachidonic acid derivatives level in blood and urine

  30. Plasma concentrations of several metabolic pathways - Endocannabinoids [ Time Frame: Through study completion (90 days following the enrollment) ]
    Endocannabinoids level in blood and urine


Biospecimen Retention:   Samples With DNA

Biological samples include:

  • blood
  • urine
  • nasopharyngeal swab
  • tracheal suction


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The target population is a population infected with SARS-CoV2 and justifying hospitalisation in an intensive care unit, i.e. presenting at least one immediate vital failure that would lead in short term to the death of the patient without the implementation of an adapted active therapeutic intervention. As the variable of interest is immuno-inflammatory activation, patients with an immune deficiency of any origin will be excluded. Patients will be recruited from patients admitted to the intensive care unit with biological confirmation of SARS-Cov2 infection.
Criteria

Inclusion Criteria:

  • Patient admitted to intensive care unit with confirmed SARS-CoV2 infection
  • Patient older than 18 years old

Exclusion Criteria:

  • Patient coming from another intensive care unit after more than 5 days in the intensive care unit
  • Known immunosuppression:

    • Known or suspected HIV
    • Known or suspected immunosuppression :
    • Organ transplantation
    • Marrow transplant
    • Congenital deficit
    • Received immunosuppressive therapy within 30 days (azathioprine, methotrexate, tacrolimus, cyclosporine, sirolimus, cyclophosphamide, rituximab, anti-TNF, JAK inhibitors, corticosteroids >10mg/day over the last 30 days, recent covid-19 corticosteroid therapy >1mg/kg prednisolone or equivalent >5 days)
    • Administration of chemotherapy within the last 3 months
  • Current pregnancy or breastfeeding
  • Patient under 18 years of age
  • Incapacitated adults and persons deprived of their liberty
  • Refusal by the patient or his/her support person

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04365166


Contacts
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Contact: Nicolas LIBERT, MD, PhD 141466772 ext +33 nicolas.libert@intradef.gouv.fr

Locations
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France
Percy Military Teaching Hospital Recruiting
Clamart, France, 92140
Contact: Nicolas LIBERT, MD, PhD    141466772 ext +33    nicolas.libert@intradef.gouv.fr   
Bégin Military Teaching Hospital Not yet recruiting
Saint-Mandé, France, 94163
Contact: Clément DUBOST, MD, PhD    143985048 ext +33    clement.dubost@intradef.gouv.fr   
Sponsors and Collaborators
Direction Centrale du Service de Santé des Armées
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Responsible Party: Direction Centrale du Service de Santé des Armées
ClinicalTrials.gov Identifier: NCT04365166    
Other Study ID Numbers: 2020-COVID19-05
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Tract Infections
Respiratory Tract Diseases
Infection