Clinical trial NCT03510650: Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)
Official title: Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophagocytic Lymphohistiocytosis
Keywords: Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic syndrome (HPS)
critically ill
Intensive care unit (ICU)
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2018-04-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female critically ill patients admitted to any ICU of the Charité - Universitätsmedizin Berlin.

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Female patients: Pregnancy
* Female patients: Breastfeeding

Primary outcomes:
measure: Incidence of HLH in intensive care units based on HLH-2004 criteria
timeFrame: Up to 180 days
Secondary outcomes:
measure: Intensive care unit stay
timeFrame: Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks
measure: Hospital stay
timeFrame: Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks
measure: Mortality
timeFrame: Up to 180 days
measure: Cytokine panel
timeFrame: Up to 180 days
measure: Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads
timeFrame: Up to 180 days
measure: Glycosylated ferritin
timeFrame: Up to 180 days
measure: microRNAs miR-205-5p, miR-194-5p and miR-30c-5p
timeFrame: Up to 180 days
measure: Perforin and CD107a
timeFrame: Up to 180 days
measure: Human immunodeficiency virus antibodies and -antigen
timeFrame: Up to 180 days
measure: Fibrinogen
timeFrame: Up to 180 days
measure: Triglycerides
timeFrame: Up to 180 days
measure: Bilirubin
timeFrame: Up to 180 days
measure: Lactate dehydrogenase
timeFrame: Up to 180 days
measure: Liver transaminase (ASAT)
timeFrame: Up to 180 days
measure: Liver transaminases (ALAT)
timeFrame: Up to 180 days
measure: Sodium
timeFrame: Up to 180 days
measure: Serum albumin
timeFrame: Up to 180 days
measure: Serum protein electrophoresis
timeFrame: Up to 180 days
measure: Detailed immune status
timeFrame: Up to 180 days
Other outcomes:
measure: HLA Typing
timeFrame: At the beginning of the investigation
Locations:
city: Berlin
country: Germany
facility: Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Claudia Spies, MD, Prof.
role: STUDY_DIRECTOR
References:
citation: Barba T, Maucort-Boulch D, Iwaz J, Bohe J, Ninet J, Hot A, Lega JC, Guerin C, Argaud L, Broussolle C, Jamilloux Y, Richard JC, Seve P. Hemophagocytic Lymphohistiocytosis in Intensive Care Unit: A 71-Case Strobe-Compliant Retrospective Study. Medicine (Baltimore). 2015 Dec;94(51):e2318. doi: 10.1097/MD.0000000000002318.
citation: Lachmann G, Knaak C, von Haefen C, Paeschke N, Meisel C, Nyvlt P, Schuster FS, Piper SK, Kruppa J, Vorderwulbecke G, Balzer F, La Rosee P, Schenk T, Unterwalder N, Kolsch U, Lachmann N, Akyuz L, Brunkhorst FM, Volk HD, Keh D, Spies C. Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients (HEMICU): a prospective observational study protocol. BMJ Open. 2019 Oct 30;9(10):e032695. doi: 10.1136/bmjopen-2019-032695.