Hemophagocytic Lymphohistiocytosis (HLH)FERRITSNCT02854943
Investigation of Ferritin in Critically Ill Patients With Hemophagocytic Lymphohistiocytosis
An observational study of Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS), run by Gunnar Lachmann.
Trial summary
Retrospective analysis of ferritin, outcome and HLH-criteria in critically ill patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis (HLH), Macrophage Activation Syndrome (MAS), Hemophagocytic Syndromes
- How many people
- 2,623 participants
- Where
- No sites listed yet
- Study dates
- Jan 2000to Aug 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Male and female critically ill patients admitted to the Charité - Universitätsmedizin Berlin during 2000 and 2018
Who may be able to join
- male and female patients
- at least one measurement of plasma ferritin
Who cannot join
- -age below 18 years
About this study
Official title: The Prognostic and Diagnostic Value of Ferritin in Critically Ill Patients With Special Focus on Underlying Hemophagocytic Lymphohistiocytosis
Retrospective analysis of ferritin, outcome and HLH-criteria in critically ill patients.
Read the detailed description
The study is a retrospective register study of critically ill patients from Charité - Universitätsmedizin Berlin during 2000 and 2016 that had at least one measurement of plasma ferritin. Outcome, underlying diagnoses and HLH-2004 criteria (Henter JI et al. 2007) will be analyzed and the HScore of these patients will be calculated (Fardet L et al. 2014). All recorded data of the specific admission term in ICU will be used for the analysis. No follow-up of the patients after discharge will be performed in this study. The study does not involve any randomization or any drug testing.
Update 2019: We expanded our database for the years until 2018 and also for the surgical and medical ICUs of the Charité - Universitätsmedizin Berlin (from 256 to 2623 patients).
Update 2022: A systematic literature search will be performed to find suitable validation cohorts for multicenter validation of optimized HLH diagnostic criteria, which are calculated based on our data (new secondary endpoint).
- Conditions
- Hemophagocytic Lymphohistiocytosis (HLH), Macrophage Activation Syndrome (MAS), Hemophagocytic Syndromes
- Keywords
- Ferritin, Hemophagocytic lymphohistiocytosis (HLH), Critically ill patients, intensive care unit (ICU), Outcome, Diagnosis
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Macrophage Activation Syndrome, Disease
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 |
|---|---|---|
| Critically ill patients | Male and female critically ill patients admitted to the Charité - University Medicine Berlin during 2000 and 2018. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
A retrospective analysis of patients with available charts to determine the outcome whether patients survived the ICU or died.
Measured: Participants will be followed up for the duration of hospital stay, an expected average of two months
Probability of having undiagnosed Hemophagocytic lymphohistiocytosis (HLH)
Retrospective analysis of available charts, underlying diagnoses, findings and blood values: HLH-2004 criteria (Henter JI et al. 2007) and HScore (Fardet L et al. 2014)
Measured: The participants will be followed up for the duration of hospital stay, an expected average of two months
Secondary outcomes (3)
Diagnoses
Retrospective analysis of available charts and underlying diagnoses
Measured: Participants will be followed up for the duration of hospital stay, an expected average of two months
Intensive care unit stay
Retrospective analysis of available charts and duration of ICU stay
Measured: Participants will be followed up for the duration of intensive care unit stay, an expected average of one week
Improving HLH diagnostic criteria including multicenter validation
Sensitivity and specificity of HLH diagnostic criteria should be improved by calculating different cutoffs of HLH-2004 criteria. Combinations with highest sensitivity and specificity will be validated in published cohorts of HLH testing for sensitivity and specificity.
Measured: Participants will be followed up for the duration of intensive care unit stay, an expected average of one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2016 (estimated)
- Study startJan 2000
- Primary completionAug 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic Lymphohistiocytosis (HLH)Studies of the same condition, open and under way.
- 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
- Retrospective
- Enrolment
- 2,623 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gunnar Lachmann
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gunnar Lachmann, Charite University, Berlin, Germany
- Investigators
- Gunnar Lachmann, MD, Study director, Charité - Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care MedicineGunnar Lachmann, MD, Study chair, Charité - Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02854943
- Sponsor's protocol ID
- HLH
- Acronym
- FERRITS
- Status last verified
- Dec 2022
- First submitted
- 1 Aug 2016
- Last updated
- 7 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
PubMed 16937360Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014 Sep;66(9):2613-20. doi: 10.1002/art.38690.
PubMed 24782338Knaak C, Schuster FS, Nyvlt P, Heeren P, Spies C, Schenk T, La Rosee P, Janka G, Brunkhorst FM, Lachmann G. Influence of transfusions, hemodialysis and extracorporeal life support on hyperferritinemia in critically ill patients. PLoS One. 2021 Jul 12;16(7):e0254345. doi: 10.1371/journal.pone.0254345. eCollection 2021.
PubMed 34252125Knaak C, Nyvlt P, Schuster FS, Spies C, Heeren P, Schenk T, Balzer F, La Rosee P, Janka G, Brunkhorst FM, Keh D, Lachmann G. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care. 2020 May 24;24(1):244. doi: 10.1186/s13054-020-02941-3.
PubMed 32448380Knaak C, Schuster FS, Spies C, Vorderwulbecke G, Nyvlt P, Schenk T, Balzer F, La Rosee P, Janka G, Brunkhorst FM, Keh D, Lachmann G. Hemophagocytic Lymphohistiocytosis in Critically Ill Patients. Shock. 2020 Jun;53(6):701-709. doi: 10.1097/SHK.0000000000001454.
PubMed 31626037Lachmann G, Spies C, Schenk T, Brunkhorst FM, Balzer F, La Rosee P. Hemophagocytic Lymphohistiocytosis: Potentially Underdiagnosed in Intensive Care Units. Shock. 2018 Aug;50(2):149-155. doi: 10.1097/SHK.0000000000001048.
PubMed 30010630
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prognostic and Diagnostic Value of Ferritin in Critically Ill Patients With Special Focus on Underlying Hemophagocytic Lymphohistiocytosis
- ClinicalTrials.gov ID
- NCT02854943
- Acronym / sponsor ID
- FERRITS / HLH
- Conditions
- Hemophagocytic Lymphohistiocytosis (HLH), Macrophage Activation Syndrome (MAS), Hemophagocytic Syndromes
- Keywords
- Ferritin, Hemophagocytic lymphohistiocytosis (HLH), Critically ill patients, intensive care unit (ICU), Outcome, Diagnosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,623 participants (actual)
- Lead sponsor
- Gunnar LachmannUniversity, hospital or other
- Study start
- Jan 2000 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 4 Aug 2016 (estimated)
- 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.
Retrospective analysis of ferritin, outcome and HLH-criteria in critically ill patients.
Detailed description
The study is a retrospective register study of critically ill patients from Charité - Universitätsmedizin Berlin during 2000 and 2016 that had at least one measurement of plasma ferritin. Outcome, underlying diagnoses and HLH-2004 criteria (Henter JI et al. 2007) will be analyzed and the HScore of these patients will be calculated (Fardet L et al. 2014). All recorded data of the specific admission term in ICU will be used for the analysis. No follow-up of the patients after discharge will be performed in this study. The study does not involve any randomization or any drug testing.
Update 2019: We expanded our database for the years until 2018 and also for the surgical and medical ICUs of the Charité - Universitätsmedizin Berlin (from 256 to 2623 patients).
Update 2022: A systematic literature search will be performed to find suitable validation cohorts for multicenter validation of optimized HLH diagnostic criteria, which are calculated based on our data (new secondary endpoint).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Critically ill patients | – | –Male and female critically ill patients admitted to the Charité - University Medicine Berlin during 2000 and 2018. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male and female critically ill patients admitted to the Charité - Universitätsmedizin Berlin during 2000 and 2018
Key inclusion criteria (2 listed)
- male and female patients
- at least one measurement of plasma ferritin
Key exclusion criteria (1 listed)
- -age below 18 years
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
Mortality
Time frame: Participants will be followed up for the duration of hospital stay, an expected average of two months
A retrospective analysis of patients with available charts to determine the outcome whether patients survived the ICU or died.
Probability of having undiagnosed Hemophagocytic lymphohistiocytosis (HLH)
Time frame: The participants will be followed up for the duration of hospital stay, an expected average of two months
Retrospective analysis of available charts, underlying diagnoses, findings and blood values: HLH-2004 criteria (Henter JI et al. 2007) and HScore (Fardet L et al. 2014)
3 secondary outcomes
Diagnoses
Time frame: Participants will be followed up for the duration of hospital stay, an expected average of two months
Intensive care unit stay
Time frame: Participants will be followed up for the duration of intensive care unit stay, an expected average of one week
Improving HLH diagnostic criteria including multicenter validation
Time frame: Participants will be followed up for the duration of intensive care unit stay, an expected average of one week
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 7 Dec 2022.
- Background: PubMed 16937360Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
- Background: PubMed 24782338Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014 Sep;66(9):2613-20. doi: 10.1002/art.38690.
- Derived from this study: PubMed 34252125Knaak C, Schuster FS, Nyvlt P, Heeren P, Spies C, Schenk T, La Rosee P, Janka G, Brunkhorst FM, Lachmann G. Influence of transfusions, hemodialysis and extracorporeal life support on hyperferritinemia in critically ill patients. PLoS One. 2021 Jul 12;16(7):e0254345. doi: 10.1371/journal.pone.0254345. eCollection 2021.
- Derived from this study: PubMed 32448380Knaak C, Nyvlt P, Schuster FS, Spies C, Heeren P, Schenk T, Balzer F, La Rosee P, Janka G, Brunkhorst FM, Keh D, Lachmann G. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care. 2020 May 24;24(1):244. doi: 10.1186/s13054-020-02941-3.
- Derived from this study: PubMed 31626037Knaak C, Schuster FS, Spies C, Vorderwulbecke G, Nyvlt P, Schenk T, Balzer F, La Rosee P, Janka G, Brunkhorst FM, Keh D, Lachmann G. Hemophagocytic Lymphohistiocytosis in Critically Ill Patients. Shock. 2020 Jun;53(6):701-709. doi: 10.1097/SHK.0000000000001454.
- Derived from this study: PubMed 30010630Lachmann G, Spies C, Schenk T, Brunkhorst FM, Balzer F, La Rosee P. Hemophagocytic Lymphohistiocytosis: Potentially Underdiagnosed in Intensive Care Units. Shock. 2018 Aug;50(2):149-155. doi: 10.1097/SHK.0000000000001048.
- 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.
Gunnar Lachmann, MD study director
Charité - Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine
Gunnar Lachmann, MD study chair
Charité - Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS), run by Gunnar Lachmann.
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 2 inclusion and 1 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 7 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
Mortality (time frame: Participants will be followed up for the duration of hospital stay, an expected average of two months). The study lists 2 primary outcomes in all. 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 NCT02854943, which also lists 6 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 7 Dec 2022.