Systemic Inflammatory Response SyndromePROPOSeNCT03604731
Persistent Multiorgan Failure in Intensive Care Units
An observational study of Systemic Inflammatory Response Syndrome and Sepsis, run by Research Institute for Complex Problems of Cardiovascular Diseases, Russia.
Trial summary
Multiorgan failure (MOF) as a result of any critical condition is a complex set of immunological and biochemical interactions leading to death in patients who are effectively subjected to primary resuscitation (correction of circulatory hypoxia in trauma and blood loss, restoration of blood circulation after… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Inflammatory Response Syndrome, Sepsis, Multiorgan Failure
- What is being tested?
- cytokine adsorbtion during extracorporeal circulation
- Type of treatment
- Medical device
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2017to 1 Sep 2020
- How long will I take part?
- 2 Years
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients operated on the heart and trunk vessels under conditions of artificial circulation (coronary artery bypass grafting, prosthetic / cardiac valve repair, operations on the aorta and its branches)
Who may be able to join
- patients after planned cardiac surgey
- informed consent
Who cannot join
- age less 18 and more then 80 years
- unplanned cardiac surgery
About this study
Official title: Persistent Multiorgan Failure in Intensive Care Units: Risk Factors, Prognosis, Outcomes
Multiorgan failure (MOF) as a result of any critical condition is a complex set of immunological and biochemical interactions leading to death in patients who are effectively subjected to primary resuscitation (correction of circulatory hypoxia in trauma and blood loss, restoration of blood circulation after operations with artificial circulation. The frequency of MOF varies depending on the primary diagnosis of a critical patient and, according to a number of authors, is 60% for sepsis, and for severe co-occurring trauma up to 40% of all critical patients. However, if one remembers that the MOF is verified only by clinical scales of assessing the severity of the patient's condition, which presupposes the presence of the already existing pathophysiological mechanisms of MOF as multi-organ dysfunction, it is possible to declare a 100% presence of MOF in all critical patients. The data of Graetz et al (2016) show that none of the available three variants of pathophysiological mechanisms (anomaly of microcirculation, persistent inflammation, immune suppression and catabolism, cellular hibernation and staning) have been unambiguously demonstrated, which also reflected the lack of effectiveness of methods therapy, proposed, based on the pathogenesis options for MOF. A so-called danger-model has a special place in the genesis of the persistence of the MOF, which justifies an active search for distress-associated and pathogen-associated molecular patterns for their objectification and probable elimination. The systemic inflammatory response in patients. included in the study, is not a primary infection. It is also important to determine the role of danger-associated molecular patterns (DAMP) in the genesis of immune suppression as the leading immunological phenotype of MOF in later periods and to evaluate the relationship between DAMP expression and immunosuppressive cells of monocyte origin. The study has a mixed (retro- and prospective) character.
Read the detailed description
- Based on the patient database analysis, by the method of continuous sampling of the cardiac surgery patients to the intensive care unit for the period 2006-2018, to determine the clinical risk factors for the development of a persistent MOF (MOF + persistent MOF, which lasts more than 7 days and is determined primarily by based on indicators of objective assessment of the patient's condition - the SOFA scale is more than 8 points on the 7th day of the critical care). To form a prognostic model.
- By means of biochemical analysis of blood serum and cells, identify biological markers MES specific for distant organs and supplement the prognostic model of persistent MOF. It is planned to detect serum concentrations (1) of surfactant protein A (organ-specific lung marker for the development of acute respiratory distress syndrome as manifestations of MOF), (2) intestinal fatty acid binding protein (organ-specific marker of acute intestinal distress (3) S100 protein - a marker of brain damage) with an assessment of prognostic and diagnostic significance with respect to the MOF.
- To assess the prognostic and diagnostic significance of serum mitochondrial DNA as one of the variants of the danger-associated molecular pattern.
- To characterize the presence of an immunosuppressive phenotype of a critical patient with MOF by examining the expression and serum concentration of: (a) myeloid suppressor cells; (b) T-reg cells expressing CD39; (c) CD62 and CD11b expression on neutrophils on monocytes; (d) soluble sTREM-1, (e) HLA-DR on monocytes. In addition, it will be planned to study the "classic" serum cytokines (tumor necrosis factor alpha, interleukin 1,6,8,10, HMGB-1).
- On the basis of the diagnostic panel obtained, to try to conduct an individualized choice of methods of preventive therapy for MOF. It is proposed to use: (1) cytokine modulation of the systemic inflammatory response by sorption of cytokines on selective sorbents, (2) cytokine modulation by sorption of cytokines on polymethylmethacrylate membranes. It is assumed that in order for these methods to be preventative, they should be used not only in conditions of treatment in the intensive care unit, but also in the operating room at the time of extracorporeal perfusion.
- Being tested
- cytokine adsorbtion during extracorporeal circulation
- Keywords
- Immunology, Suppression, Inflammation, Cardiac, Surgery
- Medical subject headings
- Systemic Inflammatory Response Syndrome, Sepsis, Multiple Organ Failure, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytokine adsorbtion during extracorporeal circulationDevice
preventive use of cytokine adsorption and modulation of the cytokine response in the course of artificial circulation
| Study group | Role | What they receive |
|---|---|---|
| Uncomplicated cardiac surgery patients | Patients after schedulled cardiac surgery procedures | |
| Complicated cardiac surgery patients | Patients after schedulled cardiac surgery procedures complicated by multiorgan failure Receives: Device: cytokine adsorbtion during extracorporeal circulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intensive Care Unit (ICU) 28 day mortality
Mortality in ICU period within 28 day
Measured: 28 day
Secondary outcomes (4)
Free of multiorgan failure (MOF) days
Free of MOF period within 28 day
Measured: 28 day
Mechanical ventilation (MV) - dependent days
MV dependens period within 28 day
Measured: 28 day
Renal Replacement Therapy (RRT) dependens
Renal Replacement Therapy period within 28 day
Measured: 28 day
Assosiation of severity of ilness
Sequential Organ Failure Assesment
Measured: 28 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start1 Jan 2017
- Primary completion1 Dec 2017
- Study completion1 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Systemic Inflammatory Response SyndromeStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Research Institute for Complex Problems of Cardiovascular Diseases, Russia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Evgeny Grigoryev, Research Institute for Complex Problems of Cardiovascular Diseases, Russia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03604731
- Sponsor's protocol ID
- 201721
- Acronym
- PROPOSe
- Status last verified
- Oct 2020
- First submitted
- 19 Jul 2018
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers. 2016 Jun 30;2:16045. doi: 10.1038/nrdp.2016.45.
PubMed 28117397Gaudilliere B, Angst MS, Hotchkiss RS. Deep Immune Profiling in Trauma and Sepsis: Flow Is the Way to Go! Crit Care Med. 2017 Sep;45(9):1577-1578. doi: 10.1097/CCM.0000000000002594. No abstract available.
PubMed 28816846Graetz TJ, Hotchkiss RS. Sepsis: Preventing organ failure in sepsis - the search continues. Nat Rev Nephrol. 2017 Jan;13(1):5-6. doi: 10.1038/nrneph.2016.171. Epub 2016 Nov 21.
PubMed 27867191Asehnoune K, Hotchkiss RS, Monneret G. Understanding why clinicians should care about danger-associated molecular patterns. Intensive Care Med. 2016 Apr;42(4):611-614. doi: 10.1007/s00134-015-4198-y. Epub 2016 Feb 24. No abstract available.
PubMed 26912314Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp. 2018 May 4;6(1):12. doi: 10.1186/s40635-018-0177-2.
PubMed 29728790Rosenthal M, Gabrielli A, Moore F. The evolution of nutritional support in long term ICU patients: from multisystem organ failure to persistent inflammation immunosuppression catabolism syndrome. Minerva Anestesiol. 2016 Jan;82(1):84-96. Epub 2015 Feb 20.
PubMed 25697882
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Persistent Multiorgan Failure in Intensive Care Units: Risk Factors, Prognosis, Outcomes
- ClinicalTrials.gov ID
- NCT03604731
- Acronym / sponsor ID
- PROPOSe / 201721
- Keywords
- Immunology, Suppression, Inflammation, Cardiac, Surgery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Research Institute for Complex Problems of Cardiovascular Diseases, RussiaUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 1 Dec 2017 (actual)
- Study completion
- 1 Sep 2020 (actual)
- First posted
- 27 Jul 2018 (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.
Multiorgan failure (MOF) as a result of any critical condition is a complex set of immunological and biochemical interactions leading to death in patients who are effectively subjected to primary resuscitation (correction of circulatory hypoxia in trauma and blood loss, restoration of blood circulation after operations with artificial circulation. The frequency of MOF varies depending on the primary diagnosis of a critical patient and, according to a number of authors, is 60% for sepsis, and for severe co-occurring trauma up to 40% of all critical patients. However, if one remembers that the MOF is verified only by clinical scales of assessing the severity of the patient's condition, which presupposes the presence of the already existing pathophysiological mechanisms of MOF as multi-organ dysfunction, it is possible to declare a 100% presence of MOF in all critical patients. The data of Graetz et al (2016) show that none of the available three variants of pathophysiological mechanisms (anomaly of microcirculation, persistent inflammation, immune suppression and catabolism, cellular hibernation and staning) have been unambiguously demonstrated, which also reflected the lack of effectiveness of methods therapy, proposed, based on the pathogenesis options for MOF. A so-called danger-model has a special place in the genesis of the persistence of the MOF, which justifies an active search for distress-associated and pathogen-associated molecular patterns for their objectification and probable elimination. The systemic inflammatory response in patients. included in the study, is not a primary infection. It is also important to determine the role of danger-associated molecular patterns (DAMP) in the genesis of immune suppression as the leading immunological phenotype of MOF in later periods and to evaluate the relationship between DAMP expression and immunosuppressive cells of monocyte origin. The study has a mixed (retro- and prospective) character.
Detailed description
- Based on the patient database analysis, by the method of continuous sampling of the cardiac surgery patients to the intensive care unit for the period 2006-2018, to determine the clinical risk factors for the development of a persistent MOF (MOF + persistent MOF, which lasts more than 7 days and is determined primarily by based on indicators of objective assessment of the patient's condition - the SOFA scale is more than 8 points on the 7th day of the critical care). To form a prognostic model.
- By means of biochemical analysis of blood serum and cells, identify biological markers MES specific for distant organs and supplement the prognostic model of persistent MOF. It is planned to detect serum concentrations (1) of surfactant protein A (organ-specific lung marker for the development of acute respiratory distress syndrome as manifestations of MOF), (2) intestinal fatty acid binding protein (organ-specific marker of acute intestinal distress (3) S100 protein - a marker of brain damage) with an assessment of prognostic and diagnostic significance with respect to the MOF.
- To assess the prognostic and diagnostic significance of serum mitochondrial DNA as one of the variants of the danger-associated molecular pattern.
- To characterize the presence of an immunosuppressive phenotype of a critical patient with MOF by examining the expression and serum concentration of: (a) myeloid suppressor cells; (b) T-reg cells expressing CD39; (c) CD62 and CD11b expression on neutrophils on monocytes; (d) soluble sTREM-1, (e) HLA-DR on monocytes. In addition, it will be planned to study the "classic" serum cytokines (tumor necrosis factor alpha, interleukin 1,6,8,10, HMGB-1).
- On the basis of the diagnostic panel obtained, to try to conduct an individualized choice of methods of preventive therapy for MOF. It is proposed to use: (1) cytokine modulation of the systemic inflammatory response by sorption of cytokines on selective sorbents, (2) cytokine modulation by sorption of cytokines on polymethylmethacrylate membranes. It is assumed that in order for these methods to be preventative, they should be used not only in conditions of treatment in the intensive care unit, but also in the operating room at the time of extracorporeal perfusion.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Uncomplicated cardiac surgery patients | – | –Patients after schedulled cardiac surgery procedures |
| Complicated cardiac surgery patients | – | Device: cytokine adsorbtion during extracorporeal circulationPatients after schedulled cardiac surgery procedures complicated by multiorgan failure |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients operated on the heart and trunk vessels under conditions of artificial circulation (coronary artery bypass grafting, prosthetic / cardiac valve repair, operations on the aorta and its branches)
Key inclusion criteria (2 listed)
- patients after planned cardiac surgey
- informed consent
Key exclusion criteria (2 listed)
- age less 18 and more then 80 years
- unplanned cardiac surgery
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 |
|---|---|---|
| cytokine adsorbtion during extracorporeal circulationpreventive use of cytokine adsorption and modulation of the cytokine response in the course of artificial circulation | Device | Complicated cardiac surgery patients |
Primary outcome
Intensive Care Unit (ICU) 28 day mortality
Time frame: 28 day
Mortality in ICU period within 28 day
4 secondary outcomes
Free of multiorgan failure (MOF) days
Time frame: 28 day
Mechanical ventilation (MV) - dependent days
Time frame: 28 day
Renal Replacement Therapy (RRT) dependens
Time frame: 28 day
Assosiation of severity of ilness
Time frame: 28 day
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 8 Oct 2020.
- Background: PubMed 28117397Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers. 2016 Jun 30;2:16045. doi: 10.1038/nrdp.2016.45.
- Background: PubMed 28816846Gaudilliere B, Angst MS, Hotchkiss RS. Deep Immune Profiling in Trauma and Sepsis: Flow Is the Way to Go! Crit Care Med. 2017 Sep;45(9):1577-1578. doi: 10.1097/CCM.0000000000002594. No abstract available.
- Background: PubMed 27867191Graetz TJ, Hotchkiss RS. Sepsis: Preventing organ failure in sepsis - the search continues. Nat Rev Nephrol. 2017 Jan;13(1):5-6. doi: 10.1038/nrneph.2016.171. Epub 2016 Nov 21.
- Background: PubMed 26912314Asehnoune K, Hotchkiss RS, Monneret G. Understanding why clinicians should care about danger-associated molecular patterns. Intensive Care Med. 2016 Apr;42(4):611-614. doi: 10.1007/s00134-015-4198-y. Epub 2016 Feb 24. No abstract available.
- Background: PubMed 29728790Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp. 2018 May 4;6(1):12. doi: 10.1186/s40635-018-0177-2.
- Background: PubMed 25697882Rosenthal M, Gabrielli A, Moore F. The evolution of nutritional support in long term ICU patients: from multisystem organ failure to persistent inflammation immunosuppression catabolism syndrome. Minerva Anestesiol. 2016 Jan;82(1):84-96. Epub 2015 Feb 20.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Inflammatory Response Syndrome and Sepsis, run by Research Institute for Complex Problems of Cardiovascular Diseases, Russia.
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 2 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 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Intensive Care Unit (ICU) 28 day mortality (time frame: 28 day). 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 NCT03604731, which also lists 6 linked publications.
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 8 Oct 2020.