Tissue InjuryNCT03986736
Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma
An observational study of Tissue Injury and Major Trauma, run by University Hospital Ostrava at 1 site in Czechia.
Trial summary
Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tissue Injury, Major Trauma, Rhabdomyolysis
- What is being tested?
- Laboratory analysis - upon admission and Laboratory analysis - 24 hours after injury
- How many people
- 150 participants
- Where
- 1 siteCzechia
- Study dates
- 15 Jun 2019to 31 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with the diagnosis of polytrauma.
Who may be able to join
- diagnosis of polytrauma
- ISS ≥ 16
Who cannot join
- history of a significant kidney impairment
- pregnancy
- injuries incompatible with life, with anticipated survival < 24 hours
- transfer to palliative care within the first 24 hours after injury
- death within the first 24 hours after injury
Trial locations and contacts
1 site in 1 country.
Czechia1 site
University Hospital Ostrava
Ostrava, Moravian-Silesian Region, 708 52
About this study
Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma.
Read the detailed description
Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma. Limited literary sources describe a correlation between the mitochondrial DNA (mDNA) and the value of plasma creatine kinase (sCK) (which is released from the injured muscles), which suggests a possible correlation between the number of released alarmins and the degree of rhabdomyolysis (damage of striated muscles). Rhabdomyolysis is further - due to the direct nephrotoxicity of myoglobin (sMb) released from the injured muscles - a significant factor participating in the development of acute renal failure in patients with serious injuries. Considering the fact that the serious injury need not include a vast damage of the muscle mass (especially in traumas with a minimal impairment of extremities), the correlation between the DAMPs and sCK/sMb values need not be constant in relation to the extent and localization of the injury defined with the AIS (Abbreviated Injury Scale) and ISS (Injury Severity Scale) scales. The DAMPs released from injured tissues immediately after trauma include HMGB-1 (high mobility group box 1); a correlation has been observed between the early post-injury levels of HMGB-1 and unfavorable outcome (defined with development of organ dysfunctions and increased mortality). Considering the fact that the DAMPs examination (including HMGB-1) are routinely available, and are also rather expensive, they are not a standard part of examinations performed in patients with serious trauma. Determination of correlation between HMGB-1 and the routinely available examinations of sCK and sMb would make the use of sCK and sMb examinations as direct indicators of mechanical tissue damage. Furthermore, this data has a significant descriptive impact in case of direct inclusion of sCK and sMb into predictive scoring systems, which currently do not contain relevant physiological parameters correlating with the extent of the injury.
In the second part of the study, the authors will concentrate upon evaluation of correlation of HMGB-1, serum creatine kinase and serum myoglobin in relation to the development of acute kidney injury (AKI), and in relation to the values of AKI markers, specifically NGAL (neutrophil-gelatinase associated lipocalin). The currently used AKI criteria are based upon relatively imprecise and late parameters (urine output, level of serum creatinine), and that is why AKI is identified in the clinical practice only in the stage of advanced and irreversible morphological and functional changes of kidneys.
The aims of the study are the following:
- To verify the correlation between the levels of circulating alarmins (HMGB-1) and the levels of sCK and sMb
- To identify the correlation between the levels of circulating alarmins and localization of the injury (according to AIS and ISS scoring systems)
- Mutual comparison of predictive levels of sCK and sMb in relation to the development of post-injury kidney failure
- Mutual comparison of predictive levels of sCK and sMb in relation to the serum and urine levels of AKI biomarkers
- Comparison of predictive levels of serum and urine NGAL in relation to the development of post-injury AKI
- Conditions
- Tissue Injury, Major Trauma, Rhabdomyolysis
- Being tested
- Laboratory analysis - upon admission, Laboratory analysis - 24 hours after injury
- Keywords
- rhabdomyolysis, tissue injury, alarmins, major trauma, acute kidney injury
- Medical subject headings
- Rhabdomyolysis, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory analysis - upon admissionDiagnostic test
Laboratory analysis will be performed upon admission of the patient to the hospital. Levels of the following parameters will be determined: HMGB-1, sCK, sMb, serum NGAL, and urine NGAL
Laboratory analysis - 24 hours after injuryDiagnostic test
Laboratory analysis will be performed upon admission of the patient to the hospital. Levels of the following parameters will be determined: sCK, sMb, serum NGAL, and urine NGAL
| Study group | Role | What they receive |
|---|---|---|
| Patients with major trauma | Patients with major trauma will be included in the study. Receives: Diagnostic Test: Laboratory analysis - upon admission; Diagnostic Test: Laboratory analysis - 24 hours after injury |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between HMGB-1 and sCK/sMb levels
Correlation between HMGB-1 and sCK/sMb levels will be assessed.
Measured: 24 hours
Correlation between sCK/sMb levels in relation to the degree and localisation of injury
Correlation between sCK/sMb levels in relation to the degree and localisation of injury will be assessed according to the AIS and ISS scoring scales.
Measured: 24 hours
Mutual comparison of predictive levels of sCK/sMb in relation to post-injury acute kidney injury defined by KDIGO criteria
Mutual comparison of predictive levels of sCK/sMb in relation to development of post-injury acute kidney injury (defined by KDIGO criteria based both on serum creatine level investigated daily and urine output collected hourly from time of admission to Day 8 after injury) development will be assessed.
Measured: 8 days
Mutual comparison of predictive levels of sCK/sMb in relation to serum and urine AKI biomarkers neutropil-gelatinase associated lipocalin (NGAL)
Mutual comparison of predictive levels of sCK/sMb in relation to serum and urine AKI biomarker NGAL will be assessed.
Measured: 8 days
Comparison of predictive levels of serum and urine NGAL in relation to post-injury acute kidney injury development defined by KDIGO criteria.
Comparison of predictive levels of serum and urine NGAL in relation to post-injury acute kidney injury (defined by KDIGO criteria based both on serum creatine level investigated daily and urine output collected hourly from time of admission to Day 8 after injury) development will be assessed.
Measured: 8 days
Secondary outcomes (2)
Reliability of HMGB-1 in predicting major blood loss in patients with severe trauma
The correlation between the HMGB-1 levels and the blood loss (in ml) will be observed in patients with severe trauma
Measured: 8 days
Reliability of HMGB-1 and other DAMPS in predicting organ dysfunction in intensive care unit patients
The correlation between HMGB-1 and other DAMPS levels and the occurrence of organ dysfunction will be observed in intensive care unit patients
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start15 Jun 2019
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tissue InjuryStudies 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Ostrava
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michal Frelich, MD,PhD, Principal investigator, University Hospital Ostrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03986736
- Sponsor's protocol ID
- FNO-KARIM-11-Rhabdomyolysis
- Other IDs
- RVO-FNOs/2019-19
- Status last verified
- Mar 2024
- First submitted
- 4 Jun 2019
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data available to other researchers.
Publications
Frelich M, Bebej M, Pavlicek J, Bursa F, Vodicka V, Svagera Z, Konde A, Jor O, Bilena M, Romanova T, Sklienka P. HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma. Sci Rep. 2025 Feb 7;15(1):4651. doi: 10.1038/s41598-025-89139-1.
PubMed 39920329
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma
- ClinicalTrials.gov ID
- NCT03986736
- Acronym / sponsor ID
- FNO-KARIM-11-Rhabdomyolysis
- Conditions
- Tissue Injury, Major Trauma, Rhabdomyolysis
- Keywords
- rhabdomyolysis, tissue injury, alarmins, major trauma, acute kidney injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University Hospital OstravaUniversity, hospital or other
- Study start
- 15 Jun 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 14 Jun 2019 (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.
Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma.
Detailed description
Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma. Limited literary sources describe a correlation between the mitochondrial DNA (mDNA) and the value of plasma creatine kinase (sCK) (which is released from the injured muscles), which suggests a possible correlation between the number of released alarmins and the degree of rhabdomyolysis (damage of striated muscles). Rhabdomyolysis is further - due to the direct nephrotoxicity of myoglobin (sMb) released from the injured muscles - a significant factor participating in the development of acute renal failure in patients with serious injuries. Considering the fact that the serious injury need not include a vast damage of the muscle mass (especially in traumas with a minimal impairment of extremities), the correlation between the DAMPs and sCK/sMb values need not be constant in relation to the extent and localization of the injury defined with the AIS (Abbreviated Injury Scale) and ISS (Injury Severity Scale) scales. The DAMPs released from injured tissues immediately after trauma include HMGB-1 (high mobility group box 1); a correlation has been observed between the early post-injury levels of HMGB-1 and unfavorable outcome (defined with development of organ dysfunctions and increased mortality). Considering the fact that the DAMPs examination (including HMGB-1) are routinely available, and are also rather expensive, they are not a standard part of examinations performed in patients with serious trauma. Determination of correlation between HMGB-1 and the routinely available examinations of sCK and sMb would make the use of sCK and sMb examinations as direct indicators of mechanical tissue damage. Furthermore, this data has a significant descriptive impact in case of direct inclusion of sCK and sMb into predictive scoring systems, which currently do not contain relevant physiological parameters correlating with the extent of the injury.
In the second part of the study, the authors will concentrate upon evaluation of correlation of HMGB-1, serum creatine kinase and serum myoglobin in relation to the development of acute kidney injury (AKI), and in relation to the values of AKI markers, specifically NGAL (neutrophil-gelatinase associated lipocalin). The currently used AKI criteria are based upon relatively imprecise and late parameters (urine output, level of serum creatinine), and that is why AKI is identified in the clinical practice only in the stage of advanced and irreversible morphological and functional changes of kidneys.
The aims of the study are the following:
- To verify the correlation between the levels of circulating alarmins (HMGB-1) and the levels of sCK and sMb
- To identify the correlation between the levels of circulating alarmins and localization of the injury (according to AIS and ISS scoring systems)
- Mutual comparison of predictive levels of sCK and sMb in relation to the development of post-injury kidney failure
- Mutual comparison of predictive levels of sCK and sMb in relation to the serum and urine levels of AKI biomarkers
- Comparison of predictive levels of serum and urine NGAL in relation to the development of post-injury AKI
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with major trauma | – | Diagnostic Test: Laboratory analysis - upon admission, Diagnostic Test: Laboratory analysis - 24 hours after injuryPatients with major trauma will be included in the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with the diagnosis of polytrauma.
Key inclusion criteria (2 listed)
- diagnosis of polytrauma
- ISS ≥ 16
Key exclusion criteria (5 listed)
- history of a significant kidney impairment
- pregnancy
- injuries incompatible with life, with anticipated survival < 24 hours
- transfer to palliative care within the first 24 hours after injury
- death within the first 24 hours after injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory analysis - upon admissionLaboratory analysis will be performed upon admission of the patient to the hospital. Levels of the following parameters will be determined: HMGB-1, sCK, sMb, serum NGAL, and urine NGAL | Diagnostic test | Patients with major trauma |
| Laboratory analysis - 24 hours after injuryLaboratory analysis will be performed upon admission of the patient to the hospital. Levels of the following parameters will be determined: sCK, sMb, serum NGAL, and urine NGAL | Diagnostic test | Patients with major trauma |
Primary outcome
Correlation between HMGB-1 and sCK/sMb levels
Time frame: 24 hours
Correlation between HMGB-1 and sCK/sMb levels will be assessed.
Correlation between sCK/sMb levels in relation to the degree and localisation of injury
Time frame: 24 hours
Correlation between sCK/sMb levels in relation to the degree and localisation of injury will be assessed according to the AIS and ISS scoring scales.
Mutual comparison of predictive levels of sCK/sMb in relation to post-injury acute kidney injury defined by KDIGO criteria
Time frame: 8 days
Mutual comparison of predictive levels of sCK/sMb in relation to development of post-injury acute kidney injury (defined by KDIGO criteria based both on serum creatine level investigated daily and urine output collected hourly from time of admission to Day 8 after injury) development will be assessed.
Mutual comparison of predictive levels of sCK/sMb in relation to serum and urine AKI biomarkers neutropil-gelatinase associated lipocalin (NGAL)
Time frame: 8 days
Mutual comparison of predictive levels of sCK/sMb in relation to serum and urine AKI biomarker NGAL will be assessed.
Comparison of predictive levels of serum and urine NGAL in relation to post-injury acute kidney injury development defined by KDIGO criteria.
Time frame: 8 days
Comparison of predictive levels of serum and urine NGAL in relation to post-injury acute kidney injury (defined by KDIGO criteria based both on serum creatine level investigated daily and urine output collected hourly from time of admission to Day 8 after injury) development will be assessed.
2 secondary outcomes
Reliability of HMGB-1 in predicting major blood loss in patients with severe trauma
Time frame: 8 days
Reliability of HMGB-1 and other DAMPS in predicting organ dysfunction in intensive care unit patients
Time frame: 8 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 20 Mar 2024.
- Derived from this study: PubMed 39920329Frelich M, Bebej M, Pavlicek J, Bursa F, Vodicka V, Svagera Z, Konde A, Jor O, Bilena M, Romanova T, Sklienka P. HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma. Sci Rep. 2025 Feb 7;15(1):4651. doi: 10.1038/s41598-025-89139-1.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data available to other researchers.
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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.
Michal Frelich, MD,PhD principal investigator
University Hospital Ostrava
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 Tissue Injury and Major Trauma, run by University Hospital Ostrava at 1 site in Czechia.
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 5 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 20 Mar 2024. 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 Czechia. 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?
Correlation between HMGB-1 and sCK/sMb levels (time frame: 24 hours). The study lists 5 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 NCT03986736, which also lists 1 linked publication.
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 20 Mar 2024.