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

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03510650
• Other study ID #: HEMICU
• Status: Completed
• Start date: September 11, 2018
• Est. completion date: December 26, 2022

Study information

• Verified date: January 2023
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 26, 2022
• Est. primary completion date: June 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Locations

Country	Name	City	State
Germany	Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HLA Typing	HLA testing identifies the major HLA genes a person has inherited and their corresponding antigens that are present on the surface of their cells.	At the beginning of the investigation
Primary	Incidence of HLH in intensive care units based on HLH-2004 criteria	HLH patients are followed up until the end of hospital stay or death.	Up to 180 days
Secondary	Intensive care unit stay		Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks
Secondary	Hospital stay		Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks
Secondary	Mortality	Mortality after 30 and 180 days	Up to 180 days
Secondary	Cytokine panel	1 blood sample of Cytokine panel (CRP, PCT, IL-1ß, IL-6, IL-8, IL-10, IL-18, IL-33, TNF-a, IFN-?, sIL-2R, ferritin) collection at time of diagnosed HLH	Up to 180 days
Secondary	Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads	1 blood sample collection at time of diagnosed HLH	Up to 180 days
Secondary	Glycosylated ferritin	1 blood sample collection at time of diagnosed HLH	Up to 180 days
Secondary	microRNAs miR-205-5p, miR-194-5p and miR-30c-5p	1 blood sample collection at time of diagnosed HLH	Up to 180 days
Secondary	Perforin and CD107a	1 blood sample collection at time of diagnosed HLH	Up to 180 days
Secondary	Human immunodeficiency virus antibodies and -antigen	1 blood sample collection at time of diagnosed HLH	Up to 180 days
Secondary	Fibrinogen		Up to 180 days
Secondary	Triglycerides		Up to 180 days
Secondary	Bilirubin		Up to 180 days
Secondary	Lactate dehydrogenase	Lactate dehydrogenase is measured in U/l	Up to 180 days
Secondary	Liver transaminase (ASAT)	ASAT [U/l]	Up to 180 days
Secondary	Liver transaminases (ALAT)	ALAT [U/l]	Up to 180 days
Secondary	Sodium		Up to 180 days
Secondary	Serum albumin		Up to 180 days
Secondary	Serum protein electrophoresis	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.	Up to 180 days
Secondary	Detailed immune status	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.	Up to 180 days