Hemophagocytic LymphohistiocytosisNCT03510650
Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)
An observational study of Hemophagocytic Lymphohistiocytosis, run by Charite University, Berlin, Germany at 1 site in Germany.
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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 11 Sep 2018to 26 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Male and female critically ill patients admitted to any ICU of the Charité - Universitätsmedizin Berlin.
Who may be able to join
- Male or female critically ill patients
- At least 18 years old
- Suspected or diagnosed HLH
Who cannot join
- Female patients: Pregnancy
- Female patients: Breastfeeding
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin
Berlin, 13353
About this study
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.
Read the 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.
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Keywords
- Hemophagocytic Lymphohistiocytosis (HLH), Hemophagocytic syndrome (HPS), critically ill, Intensive care unit (ICU)
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients | 50 patients with sepsis versus 50 patients with HLH [anticipated] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 180 days
Secondary outcomes (19)
Intensive care unit stay
Measured: Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks
Hospital stay
Measured: Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks
Mortality
Mortality after 30 and 180 days
Measured: Up to 180 days
Cytokine panel
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
Measured: Up to 180 days
Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads
1 blood sample collection at time of diagnosed HLH
Measured: Up to 180 days
Glycosylated ferritin
1 blood sample collection at time of diagnosed HLH
Measured: Up to 180 days
microRNAs miR-205-5p, miR-194-5p and miR-30c-5p
1 blood sample collection at time of diagnosed HLH
Measured: Up to 180 days
Perforin and CD107a
1 blood sample collection at time of diagnosed HLH
Measured: Up to 180 days
Human immunodeficiency virus antibodies and -antigen
1 blood sample collection at time of diagnosed HLH
Measured: Up to 180 days
Fibrinogen
Measured: Up to 180 days
Triglycerides
Measured: Up to 180 days
Bilirubin
Measured: Up to 180 days
Lactate dehydrogenase
Lactate dehydrogenase is measured in U/l
Measured: Up to 180 days
Liver transaminase (ASAT)
ASAT [U/l]
Measured: Up to 180 days
Liver transaminases (ALAT)
ALAT [U/l]
Measured: Up to 180 days
Sodium
Measured: Up to 180 days
Serum albumin
Measured: Up to 180 days
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.
Measured: Up to 180 days
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.
Measured: Up to 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2018
- Study start11 Sep 2018
- Primary completion26 Jun 2022
- Study completion26 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Claudia Spies, Charite University, Berlin, Germany
- Investigators
- Claudia Spies, MD, Prof., Study director, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03510650
- Sponsor's protocol ID
- HEMICU
- Status last verified
- Jan 2023
- First submitted
- 5 Apr 2018
- Last updated
- 4 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26705219Lachmann 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.
PubMed 31666276
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)
- ClinicalTrials.gov ID
- NCT03510650
- Acronym / sponsor ID
- HEMICU
- Conditions
- Hemophagocytic Lymphohistiocytosis
- Keywords
- Hemophagocytic Lymphohistiocytosis (HLH), Hemophagocytic syndrome (HPS), critically ill, Intensive care unit (ICU)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 11 Sep 2018 (actual)
- Primary completion
- 26 Jun 2022 (actual)
- Study completion
- 26 Dec 2022 (actual)
- First posted
- 27 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | – | –50 patients with sepsis versus 50 patients with HLH [anticipated] |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male and female critically ill patients admitted to any ICU of the Charité - Universitätsmedizin Berlin.
Key inclusion criteria (3 listed)
- Male or female critically ill patients
- At least 18 years old
- Suspected or diagnosed HLH
Key exclusion criteria (2 listed)
- Female patients: Pregnancy
- Female patients: Breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
19 secondary outcomes
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
Hospital stay
Time frame: Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks
Mortality
Time frame: Up to 180 days
Cytokine panel
Time frame: Up to 180 days
Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads
Time frame: Up to 180 days
Glycosylated ferritin
Time frame: Up to 180 days
microRNAs miR-205-5p, miR-194-5p and miR-30c-5p
Time frame: Up to 180 days
Perforin and CD107a
Time frame: Up to 180 days
Human immunodeficiency virus antibodies and -antigen
Time frame: Up to 180 days
Fibrinogen
Time frame: Up to 180 days
Triglycerides
Time frame: Up to 180 days
Bilirubin
Time frame: Up to 180 days
Lactate dehydrogenase
Time frame: Up to 180 days
Liver transaminase (ASAT)
Time frame: Up to 180 days
Liver transaminases (ALAT)
Time frame: Up to 180 days
Sodium
Time frame: Up to 180 days
Serum albumin
Time frame: Up to 180 days
Serum protein electrophoresis
Time frame: Up to 180 days
Detailed immune status
Time frame: Up to 180 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2023.
- Background: PubMed 26705219Barba 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.
- Derived from this study: PubMed 31666276Lachmann 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Spies, MD, Prof. study director
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophagocytic Lymphohistiocytosis, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of HLH in intensive care units based on HLH-2004 criteria (time frame: Up to 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03510650, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.