Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03604731
Other study ID # 201721
Secondary ID
Status Completed
Phase
First received
Last updated
Start date January 1, 2017
Est. completion date September 1, 2020

Study information

Verified date October 2020
Source Research Institute for Complex Problems of Cardiovascular Diseases, Russia
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical 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 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.


Description:

1. 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.

2. 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.

3. To assess the prognostic and diagnostic significance of serum mitochondrial DNA as one of the variants of the danger-associated molecular pattern.

4. 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).

5. 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.


Recruitment information / eligibility

Status Completed
Enrollment 300
Est. completion date September 1, 2020
Est. primary completion date December 1, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria:

- patients after planned cardiac surgey

- informed consent

Exclusion Criteria:

- age less 18 and more then 80 years

- unplanned cardiac surgery

Study Design


Related Conditions & MeSH terms


Intervention

Device:
cytokine adsorbtion during extracorporeal circulation
preventive use of cytokine adsorption and modulation of the cytokine response in the course of artificial circulation

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Research Institute for Complex Problems of Cardiovascular Diseases, Russia

References & Publications (6)

Asehnoune 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. — View Citation

Gaudilliere 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. — View Citation

Graetz 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. — View Citation

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. Review. — View Citation

Malard 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. — View Citation

Rosenthal 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. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Intensive Care Unit (ICU) 28 day mortality Mortality in ICU period within 28 day 28 day
Secondary Free of multiorgan failure (MOF) days Free of MOF period within 28 day 28 day
Secondary Mechanical ventilation (MV) - dependent days MV dependens period within 28 day 28 day
Secondary Renal Replacement Therapy (RRT) dependens Renal Replacement Therapy period within 28 day 28 day
Secondary Assosiation of severity of ilness Sequential Organ Failure Assesment 28 day
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05095324 - The Biomarker Prediction Model of Septic Risk in Infected Patients
Completed NCT02714595 - Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens Phase 3
Completed NCT03644030 - Phase Angle, Lean Body Mass Index and Tissue Edema and Immediate Outcome of Cardiac Surgery Patients
Completed NCT02867267 - The Efficacy and Safety of Ta1 for Sepsis Phase 3
Completed NCT04804306 - Sepsis Post Market Clinical Utility Simple Endpoint Study - HUMC
Recruiting NCT05578196 - Fecal Microbial Transplantation in Critically Ill Patients With Severe Infections. N/A
Terminated NCT04117568 - The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
Completed NCT03550794 - Thiamine as a Renal Protective Agent in Septic Shock Phase 2
Completed NCT04332861 - Evaluation of Infection in Obstructing Urolithiasis
Completed NCT04227652 - Control of Fever in Septic Patients N/A
Enrolling by invitation NCT05052203 - Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Recruiting NCT04005001 - Machine Learning Sepsis Alert Notification Using Clinical Data Phase 2
Completed NCT03258684 - Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis and Septic Shock N/A
Recruiting NCT05217836 - Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
Completed NCT05018546 - Safety and Efficacy of Different Irrigation System in Retrograde Intrarenal Surgery N/A
Completed NCT03295825 - Heparin Binding Protein in Early Sepsis Diagnosis N/A
Not yet recruiting NCT06045130 - PUFAs in Preterm Infants
Not yet recruiting NCT05361135 - 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia N/A
Not yet recruiting NCT05443854 - Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01) Phase 3