Clinical trial NCT03986736: Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma
Official title: Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tissue Injury
Major Trauma
Rhabdomyolysis
Keywords: rhabdomyolysis
tissue injury
alarmins
major trauma
acute kidney injury
Lead sponsor: University Hospital Ostrava
Sponsor class: OTHER
First posted: 2019-06-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with the diagnosis of polytrauma.

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Correlation between HMGB-1 and sCK/sMb levels
timeFrame: 24 hours
measure: Correlation between sCK/sMb levels in relation to the degree and localisation of injury
timeFrame: 24 hours
measure: Mutual comparison of predictive levels of sCK/sMb in relation to post-injury acute kidney injury defined by KDIGO criteria
timeFrame: 8 days
measure: Mutual comparison of predictive levels of sCK/sMb in relation to serum and urine AKI biomarkers neutropil-gelatinase associated lipocalin (NGAL)
timeFrame: 8 days
measure: Comparison of predictive levels of serum and urine NGAL in relation to post-injury acute kidney injury development defined by KDIGO criteria.
timeFrame: 8 days
Secondary outcomes:
measure: Reliability of HMGB-1 in predicting major blood loss in patients with severe trauma
timeFrame: 8 days
measure: Reliability of HMGB-1 and other DAMPS in predicting organ dysfunction in intensive care unit patients
timeFrame: 8 days
Other outcomes:
Locations:
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
state: Moravian-Silesian Region
Study officials:
affiliation: University Hospital Ostrava
name: Michal Frelich, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: