Clinical trial NCT01849237: Russian Clinical Trial of Mesenchymal Cells in Patients With Septic Shock and Severe Neutropenia
Official title: Russian Single-center Open Randomized Clinical Trial of the Impact of Mesenchymal Stromal Cells Therapy on Organ Dysfunction and 28-day Mortality in Patients With Septic Shock and Severe Neutropenia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Septic Shock
Nonchemotherapy Drug-induced Neutropenia
Neutropenia After Chemotherapy in Oncohematological Patients
Neutropenia in Patients With Aplastic Anemia
Keywords: Mesenchymal Stromal Cells
Septic Shock
Neutropenia
Procalcitonin
Interleukin-6
Interleukin-10
C-reactive protein
Survival
Organ dysfunction
Lead sponsor: National Research Center for Hematology, Russia
Sponsor class: NETWORK
First posted: 2013-05-08
Enrollment: 30
Sex: ALL
Minimum age (years): 17
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: mortality
timeFrame: 28 days
Secondary outcomes:
measure: Evaluation of MSC therapy effects on organ dysfunction
timeFrame: At Baseline and at day 2,3,7,14,21,28
measure: Evaluation of MSC therapy effects on systemic inflammatory parameters
timeFrame: At Baseline and at day 2,3,7,14,21,28
measure: Evaluation of MSC therapy effects on septic shock reversal
timeFrame: At Baseline and at day 2,3,7,14,21,28
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Research Center for Hematology
Study officials:
affiliation: National Research center of Hematology
name: Gennady M. Galstyan, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.