Multi-organ Failure After Severe TraumaMETAKITNCT06167512
Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma
An observational study of Multi-organ Failure After Severe Trauma, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
Severe trauma remains the leading cause of death in people under 50, and is associated with high morbidity, including severe disability, with a substantial socio-economic impact. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multi-organ Failure After Severe Trauma
- How many people
- 80 participants
- Where
- 2 sitesFrance
- Study dates
- 27 Jun 2024to 27 Oct 2025
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: polytrauma patients : a population of severe trauma patients at risk of failure secondary organs. healthy volonteers
Who may be able to join
- Trauma patients :
- Adult patients (age ≥ 18 years)
- Patient admitted for suspected severe trauma (1 Vittel criteria)
- Injury Severity Score ≥ 9
- Health insurance
- Written consent obtained from the patient or trusted support person / family member / close friend, or inclusion in an emergency situation and written consent obtained from the patient (trusted support person / family member / close friend if necessary) as soon as possible (article L1122-1-2 of the CSP).
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- Healthy volunteers :
- Adult patients (≥ 18 years)
- Affiliated with health insurance
- Written informed consent́
- Patient respecting matching
Who cannot join
- Trauma patients :
- Pregnant patient
- Minor patient
- Adult under guardianship, curatorship or safeguard of justice
- Patient under Aide Médicale d'État
- Chronic renal failure on dialysis
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- Chronic respiratory disease
- Patient with chronic cardiac insufficiency
- Systemic inflammatory disease
- Healthy volunteers :
- Pregnant patient
- Minor patient
- Adult under guardianship, curatorship or safeguard of justice
- Patient under Aide Médicale d'État
- Patient with chronic renal failure on dialysis
- Chronic respiratory disease
- Patient with chronic cardiac insufficiency
- Systemic inflammatory disease
Trial locations and contacts
2 sites in 1 country.
France2 sites, 2 recruiting
- Recruiting
Bicetre hospital
Le Kremlin-Bicêtre, 94250
Marie Werner, 01 45 21 34 41, marie.werner@aphp.fr
- Not yet recruiting
Bicetre hospital
Le Kremlin-Bicêtre, 94250
Laurent Becquemont, 01 47 10 77 87, laurent.becquemont@aphp.fr
About this study
Severe trauma remains the leading cause of death in people under 50, and is associated with high morbidity, including severe disability, with a substantial socio-economic impact. Secondary to trauma, multiple mechanisms (inflammatory, ischemic, oxidative, etc.) setting in rapidly, leads to organ failure, one of the three first cause of death. Vascular damage, with vasoplegia, renal damage, with acute kidney injury (AKI), and pulmonary damage, with acute respiratory distress syndrome (ARDS), are the most frequently observed but all organs can be affected whatever the type of trauma. For these reasons, identifying the pathophysiological pathways involved in organ failure induced by severe trauma is a major step towards limiting the morbidity and mortality induced by trauma, and proposing therapies to prevent them.
Because of the variability of lesions in these patients, and the multiplicity of pathways activated, the mechanisms involved and their causality with organ failure following severe trauma, are still poorly understood. Given their frequency and importance in terms of morbidity and mortality, the investigators decided to take a particular interest in the mechanisms leading to renal and pulmonary injury. The investigators' hypothesis is that the study of urinary and blood markers not performed as part of clinical routine would provide a better understanding of the pathophysiological mechanisms leading to organ failure secondary to severe trauma, and more specifically to renal and pulmonary injuries. With TRAUMATEC study, the investigators will explore mechanisms leading to AKI and ARDS through blood and urine samples of 60 severe trauma patients sampled over the first 48 hours after ICU admission and a reference of 20 healthy volunteers.
Read the detailed description
The investigators plan to include 60 patients over 18 years old with severe trauma, defined with an ISS≥9 and 20 healthy volunteers 18 years old as a reference group.
Blood and urine samples will be collected at ICU arrival, 12-, 24- and 48- hours after ICU admission. Specific dosages will then be realized on blood and urines to study metabolic and hormonal pathway leading to AKI and ARDS.
The primary objective of the study is to explore the association between renal metabolic changes and renal function impairment following severe trauma.
Secondary objectives are (1) to explore mitochondrial changes observed at the renal cellular level, on in vitro renal culture cells after exposure to trauma patient serum (2) to explore the association between plasma metabolic changes and renal and pulmonary function impairment following severe trauma (3) to explore the association between hormonal metabolic changes and renal and pulmonary function impairment following severe trauma (4) to explore the association between red blood cell-induced oxidative stress and renal function impairment following severe trauma (5) to explore the association between changes in the hemoglobin recycling (chelation) system and impaired renal function following severe trauma (6) to explore renal tubular damage secondary to severe trauma (7) to explore the pathophysiological mechanisms associated with pulmonary damage following severe trauma (8) to describe mortality at day 30.
- Conditions
- Multi-organ Failure After Severe Trauma
- Keywords
- Severe trauma, hemorrhagic shock, Acute kidney Injury, Acute respiratory distress syndrome, Multi-organ failure
- Medical subject headings
- Wounds and Injuries, Shock, Hemorrhagic, Acute Kidney Injury, Respiratory Distress Syndrome, Multiple Organ Failure
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 |
|---|---|---|
| polytrauma patients | polytrauma patients | |
| healthy volunteers | healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Profile of urinary metabolite concentrations measured by mass spectometry
Metabolomic study of patients urine according to AKI and compared to healthy volunteers measured by mass spectometry
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Secondary outcomes (23)
mitochondrial enzymatic activities of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
In vitro mitochondrial function of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to healthy volunteer serum assessed by enzymatic activities by Seahorse XFe96 analyzer
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
mitochondrial membrane potential of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
In vitro mitochondrial function of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to healthy volunteer serum assessed by measurement of mitochondrial membrane potential by fluorescence
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
mitochondrial Adenosine TriPhosphate (ATP) content of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
In vitro mitochondrial function of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to healthy volunteer serum assessed by measurement of ATP content by spectrofluorimetry
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
expression levels of mitochondrial of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
In vitro mitochondrial function of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to healthy volunteer serum assessed by measurement of expression levels of mitochondrial by Western-blot
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Plasma metabolite concentration profile measured by mass spectrometry
Metabolomic study of patients plasma measured by mass spectrometry according to AKI and ARDS and compared to healthy volunteers
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
advanced glycation end products (AGEs) produced by red blood cells
Measurement of oxidative stress produced by red blood cells assessed by advanced glycation end products (AGEs)
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
reactive oxygen derivatives produced by red blood cells
Measurement of oxidative stress produced by red blood cells assessed by reactive oxygen derivatives
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
erythrocyte NO production produced by red blood cells
Measurement of oxidative stress produced by red blood cells assessed by erythrocyte NO production
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
haptoglobin level
Hemoglobin recycling system assessed by haptoglobin
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
haptoglobin-hemoglobin complexes level
Hemoglobin recycling system assessed by haptoglobin-hemoglobin complexes
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
free hemoglobin level
Hemoglobin recycling system assessed by free hemoglobin
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
monocyte CD163 receptor from peripheral blood mononuclear cell (PBMC) isolation level
Hemoglobin recycling system assessed by monocyte CD163 receptor from peripheral blood mononuclear cell (PBMC) isolation
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Heme oxygenase-1 (HO-1) enzyme catabolizing heme level
Hemoglobin recycling system assessed by Heme oxygenase-1 (HO-1) enzyme catabolizing heme
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
renin-angiotensin-aldosterone (RASS) profile
Measurement of RASS
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Antidiuretic hormone (ADH) profile
Measurement of ADH
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
cortisol profile
Measurement of cortisol
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
leptine profile
Measurement of leptine
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Intensity of renal tubular injury
Renal tubular injury assessed by standard urinary markers: neutrophil gelatinase-associated lipocalin (NGAL), Kidney injury molecule 1 (KIM-1), IGFB-7, tissue inhibitor of metalloproteinases-2 (TIMP-2), cystatin C
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
hypoxemia level
Pulmonary injury during hospitalization in intensive care evaluated by hypoxemia assessed by the PaO2/FiO2 ratio
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
use of mechanical ventilation
Pulmonary injury during hospitalization in intensive care evaluated by use of mechanical ventilation
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Radiographic Assessment of Lung Edema (RALE) score
Pulmonary injury during hospitalization in intensive care evaluated by Radiographic Assessment of Lung Edema (RALE) score
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
alveolar epithelial lesions
Pulmonary injury during hospitalization in intensive care evaluated by evaluation of alveolar epithelial lesions by circulating soluble Receptor for Advanced Glycation Endproducts (sRAGE) assay.
Measured: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Death
Vital status at day 30
Measured: Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2023
- Study start27 Jun 2024
- Primary completion27 Sep 2025 (estimated)
- Study completion27 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multi-organ Failure After Severe TraumaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06167512
- Sponsor's protocol ID
- APHP231084
- Other IDs
- 2023-A01597-38
- Acronym
- METAKIT
- Status last verified
- Jul 2024
- First submitted
- 21 Nov 2023
- Last updated
- 15 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma
- ClinicalTrials.gov ID
- NCT06167512
- Acronym / sponsor ID
- METAKIT / APHP231084
- Conditions
- Multi-organ Failure After Severe Trauma
- Keywords
- Severe trauma, hemorrhagic shock, Acute kidney Injury, Acute respiratory distress syndrome, Multi-organ failure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Jun 2024 (actual)
- Primary completion
- 27 Sep 2025 (estimated)
- Study completion
- 27 Oct 2025 (estimated)
- First posted
- 12 Dec 2023 (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.
Severe trauma remains the leading cause of death in people under 50, and is associated with high morbidity, including severe disability, with a substantial socio-economic impact. Secondary to trauma, multiple mechanisms (inflammatory, ischemic, oxidative, etc.) setting in rapidly, leads to organ failure, one of the three first cause of death. Vascular damage, with vasoplegia, renal damage, with acute kidney injury (AKI), and pulmonary damage, with acute respiratory distress syndrome (ARDS), are the most frequently observed but all organs can be affected whatever the type of trauma. For these reasons, identifying the pathophysiological pathways involved in organ failure induced by severe trauma is a major step towards limiting the morbidity and mortality induced by trauma, and proposing therapies to prevent them.
Because of the variability of lesions in these patients, and the multiplicity of pathways activated, the mechanisms involved and their causality with organ failure following severe trauma, are still poorly understood. Given their frequency and importance in terms of morbidity and mortality, the investigators decided to take a particular interest in the mechanisms leading to renal and pulmonary injury. The investigators' hypothesis is that the study of urinary and blood markers not performed as part of clinical routine would provide a better understanding of the pathophysiological mechanisms leading to organ failure secondary to severe trauma, and more specifically to renal and pulmonary injuries. With TRAUMATEC study, the investigators will explore mechanisms leading to AKI and ARDS through blood and urine samples of 60 severe trauma patients sampled over the first 48 hours after ICU admission and a reference of 20 healthy volunteers.
Detailed description
The investigators plan to include 60 patients over 18 years old with severe trauma, defined with an ISS≥9 and 20 healthy volunteers 18 years old as a reference group.
Blood and urine samples will be collected at ICU arrival, 12-, 24- and 48- hours after ICU admission. Specific dosages will then be realized on blood and urines to study metabolic and hormonal pathway leading to AKI and ARDS.
The primary objective of the study is to explore the association between renal metabolic changes and renal function impairment following severe trauma.
Secondary objectives are (1) to explore mitochondrial changes observed at the renal cellular level, on in vitro renal culture cells after exposure to trauma patient serum (2) to explore the association between plasma metabolic changes and renal and pulmonary function impairment following severe trauma (3) to explore the association between hormonal metabolic changes and renal and pulmonary function impairment following severe trauma (4) to explore the association between red blood cell-induced oxidative stress and renal function impairment following severe trauma (5) to explore the association between changes in the hemoglobin recycling (chelation) system and impaired renal function following severe trauma (6) to explore renal tubular damage secondary to severe trauma (7) to explore the pathophysiological mechanisms associated with pulmonary damage following severe trauma (8) to describe mortality at day 30.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| polytrauma patients | – | –polytrauma patients |
| healthy volunteers | – | –healthy volunteers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- polytrauma patients : a population of severe trauma patients at risk of failure secondary organs. healthy volonteers
Key inclusion criteria (11 listed)
- Adult patients (age ≥ 18 years)
- Patient admitted for suspected severe trauma (1 Vittel criteria)
- Injury Severity Score ≥ 9
- Health insurance
- Written consent obtained from the patient or trusted support person / family member / close friend, or inclusion in an emergency situation and written consent obtained from the patient (trusted support person / family member / close friend if necessary) as soon as possible (article L1122-1-2 of the CSP).
Key exclusion criteria (18 listed)
- Pregnant patient
- Minor patient
- Adult under guardianship, curatorship or safeguard of justice
- Patient under Aide Médicale d'État
- Chronic renal failure on dialysis
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
Profile of urinary metabolite concentrations measured by mass spectometry
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Metabolomic study of patients urine according to AKI and compared to healthy volunteers measured by mass spectometry
23 secondary outcomes
mitochondrial enzymatic activities of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
mitochondrial membrane potential of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
mitochondrial Adenosine TriPhosphate (ATP) content of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
expression levels of mitochondrial of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Plasma metabolite concentration profile measured by mass spectrometry
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
advanced glycation end products (AGEs) produced by red blood cells
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
reactive oxygen derivatives produced by red blood cells
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
erythrocyte NO production produced by red blood cells
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
haptoglobin level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
haptoglobin-hemoglobin complexes level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
free hemoglobin level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
monocyte CD163 receptor from peripheral blood mononuclear cell (PBMC) isolation level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Heme oxygenase-1 (HO-1) enzyme catabolizing heme level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
renin-angiotensin-aldosterone (RASS) profile
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Antidiuretic hormone (ADH) profile
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
cortisol profile
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
leptine profile
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Intensity of renal tubular injury
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
hypoxemia level
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
use of mechanical ventilation
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Radiographic Assessment of Lung Edema (RALE) score
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
alveolar epithelial lesions
Time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Death
Time frame: Day 30
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2024.
- Individual participant dataSharing planned: Undecided
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multi-organ Failure After Severe Trauma, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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 11 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 15 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Profile of urinary metabolite concentrations measured by mass spectometry (time frame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2024.