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Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)

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ClinicalTrials.gov Identifier: NCT03510650
Recruitment Status : Recruiting
First Posted : April 27, 2018
Last Update Posted : January 29, 2020
Sponsor:
Information provided by (Responsible Party):
Claudia Spies, Charite University, Berlin, Germany

Brief Summary:
Hemophagocytic lymphohistiocytosis in adults (HLH) is at 68% mortality whereas 78% of all cases remain undiagnosed though therapies are available which clearly reduce mortality. The investigators aim to systematically investigate this life-threatening hyperinflammatory syndrome in intensive care units (ICU) in order to detect biomarkers that are highly sensitive and highly specific for HLH in ICU compared to patients with sepsis.

Condition or disease
Hemophagocytic Lymphohistiocytosis

Detailed Description:
The investigators will draw blood samples of 100 patients at the time of diagnosis (each 50 with suspected or diagnosed HLH/sepsis) to determine a cytokine panel (c reactive protein (CRP), procalcitonin (PCT), interleukin (IL) 1β, IL-6, IL-8, IL-10, IL-18, IL-33, tumor necrosis factor (TNF) α, interferon (IFN) ɣ, soluble IL-2 receptor (sIL-2R), the EBV and CMV viral loads, human immunodeficiency virus (HIV) antibodies and -antigen, perforin, fibrinogen, triglycerides, bilirubin, lactate dehydrogenase, liver transaminases, sodium, serum albumin, electrophoresis, glycosylated ferritin, the microRNAs miR-205-5p, miR-194-5p and miR-30c-5p, perforin, CD107a and high immune status (differential blood count, T cells, B cells, NK cells, T helper cells, cytotoxic T cells, CD4 / CD8 ratio, HLA-DR of CD8 +, CD11a of CD8, CD57 of CD8, CD28 of CD8 +, HLA-DR of monocytes, CD56bright and CD69 of NK cells). The results of this study serve the development of new clinical concepts in order to safely diagnose HLH at an early stage, to distinguish from sepsis and to reduce the fatal consequences.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : December 31, 2021

Group/Cohort
Patients
50 patients with sepsis versus 50 patients with HLH [anticipated]



Primary Outcome Measures :
  1. Incidence of HLH in intensive care units based on HLH-2004 criteria [ Time Frame: Up to 180 days ]
    HLH patients are followed up until the end of hospital stay or death.


Secondary Outcome Measures :
  1. Intensive care unit stay [ Time Frame: Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks ]
  2. Hospital stay [ Time Frame: Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks ]
  3. Mortality [ Time Frame: Up to 180 days ]
    Mortality after 30 and 180 days

  4. Cytokine panel [ Time Frame: Up to 180 days ]
    1 blood sample of Cytokine panel (CRP, PCT, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33, TNF-α, IFN-ɣ, sIL-2R, ferritin) collection at time of diagnosed HLH

  5. Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads [ Time Frame: Up to 180 days ]
    1 blood sample collection at time of diagnosed HLH

  6. Glycosylated ferritin [ Time Frame: Up to 180 days ]
    1 blood sample collection at time of diagnosed HLH

  7. microRNAs miR-205-5p, miR-194-5p and miR-30c-5p [ Time Frame: Up to 180 days ]
    1 blood sample collection at time of diagnosed HLH

  8. Perforin and CD107a [ Time Frame: Up to 180 days ]
    1 blood sample collection at time of diagnosed HLH

  9. Human immunodeficiency virus antibodies and -antigen [ Time Frame: Up to 180 days ]
    1 blood sample collection at time of diagnosed HLH

  10. Fibrinogen [ Time Frame: Up to 180 days ]
  11. Triglycerides [ Time Frame: Up to 180 days ]
  12. Bilirubin [ Time Frame: Up to 180 days ]
  13. Lactate dehydrogenase [ Time Frame: Up to 180 days ]
    Lactate dehydrogenase is measured in U/l

  14. Liver transaminase (ASAT) [ Time Frame: Up to 180 days ]
    ASAT [U/l]

  15. Liver transaminases (ALAT) [ Time Frame: Up to 180 days ]
    ALAT [U/l]

  16. Sodium [ Time Frame: Up to 180 days ]
  17. Serum albumin [ Time Frame: Up to 180 days ]
  18. Serum protein electrophoresis [ Time Frame: Up to 180 days ]
    Serum protein Electrophoresis (%) is used to separate and quantify the serum protein components into serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma Globulins.

  19. Detailed immune status [ Time Frame: Up to 180 days ]
    The immune status is analyzed by differential blood count [/nl], T cells [/nl], B cells [/nl], NK cells [/nl], T helper cells [/nl], cytotoxic T cells [/nl], CD4 / CD8 ratio, HLA-DR of CD8+ [%], CD11a of CD8 [%], CD57 of CD8 [%], CD28 of CD8+ [%], HLA-DR of monocytes [antigen/cell], CD56bright [%] and CD69 [%] of NK cells.


Other Outcome Measures:
  1. HLA Typing [ Time Frame: At the beginning of the investigation ]
    HLA testing identifies the major HLA genes a person has inherited and their corresponding antigens that are present on the surface of their cells.


Biospecimen Retention:   Samples With DNA
6 ml of blood samples of each patient will be stored in the Biobank of the Berlin Institute of Health, Clinical Research Unit, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Male and female critically ill patients admitted to any ICU of the Charité - Universitätsmedizin Berlin.
Criteria

Inclusion Criteria:

  • Male or female critically ill patients
  • At least 18 years old
  • Suspected or diagnosed HLH or sepsis

Exclusion Criteria:

  • Female patients: Pregnancy
  • Female patients: Breastfeeding

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): NCT03510650


Contacts
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Contact: Claudia Spies, MD, Prof. +49 30 450 55 10 01 claudia.spies@charite.de

Locations
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Germany
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Contact: Claudia Spies, MD, Prof.    +49 30 450 55 11 33    claudia.spies@charite.de   
Principal Investigator: Claudia Spies, MD, Prof.         
Sub-Investigator: Gunnar Lachmann, MD         
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
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Study Director: Claudia Spies, MD, Prof. Charite University, Berlin, Germany

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Claudia Spies, Head of the Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT03510650    
Other Study ID Numbers: HEMICU
First Posted: April 27, 2018    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Claudia Spies, Charite University, Berlin, Germany:
Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic syndrome (HPS)
critically ill
Intensive care unit (ICU)
Additional relevant MeSH terms:
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Lymphohistiocytosis, Hemophagocytic
Critical Illness
Disease Attributes
Pathologic Processes
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases