Septic ShockPhase 1/2NCT01849237
Russian Clinical Trial of Mesenchymal Cells in Patients With Septic Shock and Severe Neutropenia
A Phase 1/2 study testing Mesenchymal stromal cells and Standard therapy of septic shock in people with Septic Shock and Nonchemotherapy Drug-induced Neutropenia, run by National Research Center for Hematology, Russia at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 17 to 75 years
- Conditions the study is for
- Septic Shock, Nonchemotherapy Drug-induced Neutropenia, Neutropenia After Chemotherapy in Oncohematological Patients
- What is being tested?
- Mesenchymal stromal cells and Standard therapy of septic shock
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteRussia
- Study dates
- Dec 2012to May 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- septic shock
- ≤10 hs after onset of septic shock severe neutropenia(≤ 1 10^9/l) Patients ≥17 years Signed Informed Consent to treatment
Who cannot join
- oncohematological patients with resistance to chemotherapy Unsigned Informed Consent to treatment Age >75 years; Pregnancy
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
National Research Center for Hematology
Moscow, 125167
Gennady M Galstyan, MD PhD, +7(495)6124859, gengalst@gmail.com
: Gennady M. Galstyan,, MD PhD
About this study
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.
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.
Read more
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).
Read the 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
- Being tested
- Mesenchymal stromal cells, Standard therapy of septic shock
- Keywords
- Mesenchymal Stromal Cells, Septic Shock, Neutropenia, Procalcitonin, Interleukin-6, Interleukin-10, C-reactive protein, Survival, Organ dysfunction
- Medical subject headings
- Shock, Septic, Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stromal cellsGenetic
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 shockDrug
Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids
| Study group | Role | What they receive |
|---|---|---|
| Standard therapy of septic shock | Active comparator | according to Surviving Sepsis Campaign 2012 Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids Receives: Drug: Standard therapy of septic shock |
| 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 Receives: Genetic: Mesenchymal stromal cells; Drug: Standard therapy of septic shock |
What is being measured
The primary outcome is the main question the study is designed to answer.
mortality
Measured: 28 days
Secondary outcomes (3)
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)
Measured: 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
Measured: At Baseline and at day 2,3,7,14,21,28
Evaluation of MSC therapy effects on septic shock reversal
SOFA score
Measured: At Baseline and at day 2,3,7,14,21,28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startDec 2012
- Primary completionApr 2013
- Study completionMay 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Research Center for Hematology, Russia
- Sponsor type
- Research network
- Responsible party
- Principal investigator, Elena N.Parovichnikova, National Research Center for Hematology, Russia
- Investigators
- Gennady M. Galstyan, MD PhD, Principal investigator, National Research center of Hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849237
- Sponsor's protocol ID
- RuMCeSS
- Status last verified
- May 2013
- First submitted
- 1 May 2013
- Last updated
- 10 May 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23361625Mei 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.
PubMed 20558630Kebriaei 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.
PubMed 21231805
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01849237
- Acronym / sponsor ID
- RuMCeSS
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National Research Center for Hematology, RussiaResearch network
- Study start
- Dec 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- May 2015 (estimated)
- First posted
- 8 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard therapy of septic shock | Active comparator | Drug: Standard therapy of septic shockaccording to Surviving Sepsis Campaign 2012 Antibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids |
| Mesenchymal stromal cells+ standard therapy of septic shock | Experimental | Genetic: Mesenchymal stromal cells, Drug: Standard therapy of septic shockMSCs 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 |
Who may qualify
- Ages
- 17 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- septic shock
- ≤10 hs after onset of septic shock severe neutropenia(≤ 1 10^9/l) Patients ≥17 years Signed Informed Consent to treatment
Key exclusion criteria (1 listed)
- oncohematological patients with resistance to chemotherapy Unsigned Informed Consent to treatment Age >75 years; Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal stromal cellsMSCs 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). | Genetic | Mesenchymal stromal cells+ standard therapy of septic shock |
| Standard therapy of septic shockAntibiotic therapy Fluid therapy Vasopressors Inotropic therapy Steroids | Drug | Mesenchymal stromal cells+ standard therapy of septic shock, Standard therapy of septic shock |
Primary outcome
mortality
Time frame: 28 days
3 secondary outcomes
Evaluation of MSC therapy effects on organ dysfunction
Time frame: At Baseline and at day 2,3,7,14,21,28
Evaluation of MSC therapy effects on systemic inflammatory parameters
Time frame: At Baseline and at day 2,3,7,14,21,28
Evaluation of MSC therapy effects on septic shock reversal
Time frame: At Baseline and at day 2,3,7,14,21,28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2013.
- Background: PubMed 23361625Dellinger 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.
- Background: PubMed 20558630Mei 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.
- Background: PubMed 21231805Kebriaei 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gennady M. Galstyan, MD PhD principal investigator
National Research center of Hematology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal stromal cells and Standard therapy of septic shock in people with Septic Shock and Nonchemotherapy Drug-induced Neutropenia, run by National Research Center for Hematology, Russia at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gennady Galstyan, MD PhD (+7(495)6124859, gengalst@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01849237, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2013.