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

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03510650
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Anticipated Duration (Months): 51.6
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

• Study Type: Observational
• Anticipated 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: Sep 11, 2018
• Anticipated Primary Completion Date: Jul 30, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Patients 50 patients with sepsis versus 50 patients with HLH [anticipated]

Outcome Measures

Primary Outcome Measures

1. Incidence of HLH in intensive care units based on HLH-2004 criteria [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 [Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks]

2. Hospital stay [Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks]

3. Mortality [Up to 180 days]

   Mortality after 30 and 180 days

4. Cytokine panel [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 [Up to 180 days]

   1 blood sample collection at time of diagnosed HLH

6. Glycosylated ferritin [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 [Up to 180 days]

   1 blood sample collection at time of diagnosed HLH

8. Perforin and CD107a [Up to 180 days]

   1 blood sample collection at time of diagnosed HLH

9. Human immunodeficiency virus antibodies and -antigen [Up to 180 days]

   1 blood sample collection at time of diagnosed HLH

10. Fibrinogen [Up to 180 days]

11. Triglycerides [Up to 180 days]

12. Bilirubin [Up to 180 days]

13. Lactate dehydrogenase [Up to 180 days]

    Lactate dehydrogenase is measured in U/l

14. Liver transaminase (ASAT) [Up to 180 days]

    ASAT [U/l]

15. Liver transaminases (ALAT) [Up to 180 days]

    ALAT [U/l]

16. Sodium [Up to 180 days]

17. Serum albumin [Up to 180 days]

18. Serum protein electrophoresis [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin	Berlin		Germany	13353

Sponsors and Collaborators

• Charite University, Berlin, Germany

Investigators

• Study Director: Claudia Spies, MD, Prof., Charite University, Berlin, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

• Barba T, Maucort-Boulch D, Iwaz J, Bohé J, Ninet J, Hot A, Lega JC, Guérin C, Argaud L, Broussolle C, Jamilloux Y, Richard JC, Sève 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.

• 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: Apr 27, 2018
• Last Update Posted: Jul 14, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Claudia Spies, Head of the Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Charite University, Berlin, Germany: Hemophagocytic Lymphohistiocytosis (HLH); Hemophagocytic syndrome (HPS); critically ill; Intensive care unit (ICU)
• Additional relevant MeSH terms: Lymphohistiocytosis, Hemophagocytic; Critical Illness

Study Results

No Results Posted as of Jul 14, 2021