Russian Clinical Trial of Mesenchymal Cells in Patients With Septic Shock and Severe Neutropenia

NCT ID: NCT01849237

Last Updated: 2013-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-05-31

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.

Conditions

Septic Shock; Nonchemotherapy Drug-induced Neutropenia; Neutropenia After Chemotherapy in Oncohematological Patients; Neutropenia in Patients With Aplastic Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard therapy of septic shock

according to Surviving Sepsis Campaign 2012 Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids

Group Type: ACTIVE_COMPARATOR

Standard therapy of septic shock

Intervention Type: DRUG

Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids

Mesenchymal stromal cells+ standard therapy of septic shock

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

Group Type: EXPERIMENTAL

Mesenchymal stromal cells

Intervention Type: 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).

Standard therapy of septic shock

Intervention Type: DRUG

Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids

Interventions

Mesenchymal stromal cells

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).

Intervention Type: GENETIC

Standard therapy of septic shock

Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids

Intervention Type: DRUG

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

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Center for Hematology, Russia

NETWORK

Sponsor Role: lead

Responsible Party

Elena N.Parovichnikova

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gennady M. Galstyan, MD PhD

Role: PRINCIPAL_INVESTIGATOR

National Research center of Hematology

Locations

National Research Center for Hematology

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Gennady Galstyan, MD PhD

Role: CONTACT

gengalst@gmail.com

+7(495)6124859

Facility Contacts

Gennady M Galstyan, MD PhD

Role: primary

gengalst@gmail.com

+7(495)6124859

References

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.

Reference Type: BACKGROUND

PMID: 23361625 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20558630 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21231805 (View on PubMed)

Other Identifiers

RuMCeSS

Identifier Type: -

Identifier Source: org_study_id