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

Septic Shock Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01849237
• Other study ID #: RuMCeSS
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 1, 2013
• Last updated: May 8, 2013
• Start date: December 2012
• Est. completion date: May 2015

Study information

• Verified date: May 2013
• Source: National Research Center for Hematology, Russia
• Contact: Gennady Galstyan, MD PhD
• Phone: +7(495)6124859
• Email: gengalst[@]gmail.com
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2015
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Genetic:
• 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).

Drug:
• Standard therapy of septic shock
Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids

Locations

Country	Name	City	State
Russian Federation	National Research Center for Hematology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
National Research Center for Hematology, Russia

Country where clinical trial is conducted

Russian Federation, 

References & Publications (3)

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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mortality		28 days	Yes
Secondary	Evaluation of MSC therapy effects on organ dysfunction	Liver: levels of serum total bilirubin, transaminases, lactate dehydrogenase, plasma protrombin level; Pancreas: amylase level; Renal: number of hemodialysis/ hemodiafiltration, blood urea and creatinine levels; Pulmonary: requirement for mechanical ventilation or non-invasive mechanical ventilation, pulmonary function-coefficient, partial oxygen pressure arterial blood level; Cardiac: requirement for vasopressors, main parameters obtained from Transpulmonary Thermodilution- Systemic Vascular Resistance Index ( SVRI ), Cardiac Output (CO)	At Baseline and at day 2,3,7,14,21,28	Yes
Secondary	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	Yes
Secondary	Evaluation of MSC therapy effects on septic shock reversal	SOFA score	At Baseline and at day 2,3,7,14,21,28	Yes