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Septic shock remains a significant clinical problem associated with high rates of mortality among neutropenic patient despite antimicrobial therapy and supportive care. Recently, mesenchymal stromal cells (MSC) have demonstrated remarkable potential effect in sepsis. MSC treatment significantly reduced mortality in septic mice receiving appropriate antimicrobial therapy. MSCs reduced systemic inflammatory cytokine levels in mice, down-regulated of inflammation and inflammation-related genes (such as interleukin-10, interleukin-6). Bacterial clearance was greater in MSC-treated mice. Thus, MSCs have beneficial effects on experimental sepsis and suggest that MSСs-therapy may be an effective adjunctive treatment to reduce sepsis-related mortality.
The safety of MSCs is proved by Graft-versus-host disease treatment MSCs in patients after bone marrow transplantation.
This study hypothesis is that MSCs reduce organ dysfunction/injury, systemic inflammation and mortality in patients with septic shock and severe neutropenia.
The main goal of the study is to evaluate the impact of MSCs therapy on organ dysfunction/injury, systemic inflammation and 28-day mortality in patients with septic shock and severe neutropenia. All patients will be randomized in two groups: control group (standard treatment of septic shock) and MSCs-group (standard treatment of septic shock + MSCs infusion of 1-2 millions/kg/ day).
All activities related to this human subjects research have been guided by ethical principles and have been reviewed and approved Federalwide Assurance National Ctr for Hematology, FWA00006482. The goal of the trial is to evaluate plasma concentration of proinflammatory cytokine interleukin-6 and the antiinflammatory cytokine interleukin-10, plasma levels of blood creatinine, bilirubin, procalcitonin, C-reactive protein. Then we will evaluate requirement for renal replacement therapy, requirement for mechanical ventilation or non-invasive mechanical ventilation, pulmonary function-coefficient, partial oxygen pressure arterial blood level, electrocardiograms, Kaplan - Meier curve,28-days mortality.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard therapy of septic shock | Active Comparator | according to Surviving Sepsis Campaign 2012 Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids |
|
| Mesenchymal stromal cells+ standard therapy of septic shock | Experimental | MSCs intravenous infusion of 1-2 millions/kg/day will be performed not more than 10 hs after onset of septic shock in patients with severe neutropenia(≤ 1x10^9/l). according to Surviving Sepsis Campaign 2012: Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesenchymal stromal cells | Genetic | MSCs intravenous infusion of 1-2 millions/kg/day will be performed not more than 10 hs after onset of septic shock in patients with severe neutropenia(≤ 1x10^9/l). |
| Measure | Description | Time Frame |
|---|---|---|
| mortality | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of MSC therapy effects on organ dysfunction |
|
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Inclusion Criteria:
septic shock
≤10 hs after onset of septic shock severe neutropenia(≤ 1 10^9/l) Patients ≥17 years Signed Informed Consent to treatment
Exclusion Criteria:
oncohematological patients with resistance to chemotherapy Unsigned Informed Consent to treatment Age >75 years; Pregnancy
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gennady Galstyan, MD PhD | Contact | +7(495)6124859 | gengalst@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Gennady M. Galstyan, MD PhD | National Research center of Hematology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Research Center for Hematology | Recruiting | Moscow | 125167 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23361625 | Background | Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30. | |
| 20558630 |
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| Standard therapy of septic shock | Drug | Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids |
|
| At Baseline and at day 2,3,7,14,21,28 |
| Evaluation of MSC therapy effects on systemic inflammatory parameters | plasma concentration of proinflammatory cytokine IL-6 and the antiinflammatory cytokine IL-10, concentration of procalcitonin, C-reactive protein Fibrinogen level, lactate level , the factor XII-dependent fibrinolytic activity blood routine examination | At Baseline and at day 2,3,7,14,21,28 |
| Evaluation of MSC therapy effects on septic shock reversal | SOFA score | At Baseline and at day 2,3,7,14,21,28 |
| Background |
| Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 2010 Oct 15;182(8):1047-57. doi: 10.1164/rccm.201001-0010OC. Epub 2010 Jun 17. |
| 21231805 | Background | Kebriaei P, Robinson S. Treatment of graft-versus-host-disease with mesenchymal stromal cells. Cytotherapy. 2011 Mar;13(3):262-8. doi: 10.3109/14653249.2010.549688. Epub 2011 Jan 13. |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D009503 | Neutropenia |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D000380 | Agranulocytosis |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007960 | Leukocyte Disorders |
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