Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma

Major Trauma Clinical Trial

Official title:

Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03986736
• Other study ID #: FNO-KARIM-11-Rhabdomyolysis
• Secondary ID: RVO-FNOs/2019-19
• Status: Completed
• Start date: June 15, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2024
• Source: University Hospital Ostrava
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosis of polytrauma

• ISS = 16

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Major Trauma
• Rhabdomyolysis
• Tissue Injury
• Wounds and Injuries

Intervention

Diagnostic Test:
• Laboratory analysis - upon admission
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 injury
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

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Ostrava

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between HMGB-1 and sCK/sMb levels	Correlation between HMGB-1 and sCK/sMb levels will be assessed.	24 hours
Primary	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.	24 hours
Primary	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.	8 days
Primary	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.	8 days
Primary	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.	8 days
Secondary	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	8 days
Secondary	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	8 days