Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03986736
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Ostrava

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.

Condition or disease Intervention/treatment
Tissue Injury Major Trauma Rhabdomyolysis Diagnostic Test: Laboratory analysis - upon admission Diagnostic Test: Laboratory analysis - 24 hours after injury

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

Layout table for study information
Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma
Actual Study Start Date : June 15, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Patients with major trauma
Patients with major trauma will be included in the study.
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

Diagnostic Test: 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




Primary Outcome Measures :
  1. Correlation between HMGB-1 and sCK/sMb levels [ Time Frame: 24 hours ]
    Correlation between HMGB-1 and sCK/sMb levels will be assessed.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Biospecimen Retention:   Samples Without DNA
Two collections of full blood will be performed in the study subjects for laboratory analysis.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with the diagnosis of polytrauma.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03986736


Contacts
Layout table for location contacts
Contact: Petr Vávra, Ass.Prof.,MD,PhD 0042059737 ext 2544 petr.vavra@fno.cz
Contact: Jiří Hynčica 0042059737 ext 2587 jiri.hyncica@fno.cz

Locations
Layout table for location information
Czechia
University Hospital Ostrava Recruiting
Ostrava, Moravian-Silesian Region, Czechia, 708 52
Contact: Petr Vávra, Ass.Prof.,MD,PhD    0042059737 ext 2544    petr.vavra@fno.cz   
Contact: Jiří Hynčica    0042059737 ext 2587    jiri.hyncica@fno.cz   
Principal Investigator: Michal Frelich, MD,PhD         
Sub-Investigator: Peter Sklienka, MD,PhD         
Sub-Investigator: Vojtěch Vodička, MD         
Sub-Investigator: Zuzana Mučková, Bc.         
Sponsors and Collaborators
University Hospital Ostrava
Investigators
Layout table for investigator information
Principal Investigator: Michal Frelich, MD,PhD University Hospital Ostrava

Layout table for additonal information
Responsible Party: University Hospital Ostrava
ClinicalTrials.gov Identifier: NCT03986736     History of Changes
Other Study ID Numbers: FNO-KARIM-11-Rhabdomyolysis
RVO-FNOs/2019-19 ( Other Grant/Funding Number: University Hospital Ostrava )
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data available to other researchers.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Ostrava:
rhabdomyolysis
tissue injury
alarmins
major trauma
acute kidney injury

Additional relevant MeSH terms:
Layout table for MeSH terms
Wounds and Injuries
Rhabdomyolysis
Muscular Diseases
Musculoskeletal Diseases