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

Phase 1

• Conditions: Septic Shock; Nonchemotherapy Drug-induced Neutropenia; Neutropenia After Chemotherapy in Oncohematological Patients; Neutropenia in Patients With Aplastic Anemia
• Interventions: Drug: Standard therapy of septic shock; Genetic: Mesenchymal stromal cells

• Registration Number: NCT01849237
• Lead Sponsor: National Research Center for Hematology, Russia

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.

Study Timeline

• Study Start: 2012-12
• Primary Completion: 2013-04
• Status Verified: 2013-05
• Study First Submitted: 2013-05-01
• Study First Submitted QC: 2013-05-05
• Study First Posted: 2013-05-08
• Last Update Submitted: 2013-05-08
• Last Update Posted: 2013-05-10
• Study Completion: 2015-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapy of septic shock	Standard therapy of septic shock	according to Surviving Sepsis Campaign 2012 Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids
Mesenchymal stromal cells+ standard therapy of septic shock	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). according to Surviving Sepsis Campaign 2012: Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids
Mesenchymal stromal cells+ standard therapy of septic shock	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

Primary Outcome Measures

Name	Time	Method
mortality	28 days

Secondary Outcome Measures

Name	Time	Method
Evaluation of MSC therapy effects on organ dysfunction	At Baseline and at day 2,3,7,14,21,28	1. Liver: levels of serum total bilirubin, transaminases, lactate dehydrogenase, plasma protrombin level; 2. Pancreas: amylase level; 3. Renal: number of hemodialysis/ hemodiafiltration, blood urea and creatinine levels; 4. Pulmonary: requirement for mechanical ventilation or non-invasive mechanical ventilation, pulmonary function-coefficient, partial oxygen pressure arterial blood level; 5. Cardiac: requirement for vasopressors, main parameters obtained from Transpulmonary Thermodilution- Systemic Vascular Resistance Index ( SVRI ), Cardiac Output (CO)
Evaluation of MSC therapy effects on systemic inflammatory parameters	At Baseline and at day 2,3,7,14,21,28	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
Evaluation of MSC therapy effects on septic shock reversal	At Baseline and at day 2,3,7,14,21,28	SOFA score

Trial Locations

Locations (1)

National Research Center for Hematology; 🇷🇺 Moscow, Russian Federation