Back to resultsEfficacy of Infusions of MSC From Wharton Jelly in the SARS-Cov-2 (COVID-19) Related Acute Respiratory Distress Syndrome (MSC-COVID19)
Primary Purpose
COVID19 ARDS
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID19 ARDS focused on measuring COVID, ARDS, MSC, mesenchymal stem cells, Wharton's Jelly, inflammation
Eligibility Criteria
Inclusion Criteria:
- Man or woman 18 years of age or older
- Patient with a biologically confirmed SARS-CoV-2 infection (by positive RT-PCR on a nasopharyngeal sample or any other sample)
- Patient with moderate to severe ARDS according to the BERLIN definition defined by a PaO2 / FiO2 ratio <200 and with endotracheal intubation and under invasive mechanical ventilation
- Patient hospitalized in the intensive care unit
- Provision of a written informed consent to participate to the study or for whom the consent of a family member or support person has been obtained (if the patient is unable to give consent) or inclusion in an immediate vital emergency if applicable
- Any woman of childbearing age with a negative Beta HCG test
- Social Security affiliation
Exclusion Criteria:
- Patient under invasive mechanical ventilation for more than 48 hours
- Patient with a chronic respiratory disease under oxygen therapy
- Patients with a history of Class III or IV pulmonary arterial hypertension (WHO classification)
- Patients under ECMO
- Immunosuppressive therapy (including corticosteroid therapy> 20 mg prednisolone)
- Active solid tumor or in remission for less than 2 years, malignant hematological disease, asplenia
- Patient who has received a hematopoietic stem transplantation or an organ transplant
- Therapeutic limitations like progression to expected death within 24 hours (according to the opinion of the medical team)
- Hypersensitivity to albumin or to any of the excipients (caprylic acid or sodium caprylate)
- Patient included in another ongoing interventional therapeutic trial
- Pregnant woman, parturient, nursing mother
- Minor (not emancipated)
- Person without liberty by judiciary or administrative decision
- Person undergoing psychiatric care under Articles L. 3212-1 and L. 3213-1 which do not fall under the provisions of Article L. 1121-8 (hospitalization without consent).
- Adult over 18 who are under a legal protection measure
Sites / Locations
- Nancy University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MSC Arm
Placebo Arm
Arm Description
Ex vivo expanded Wharton's Jelly derived mesenchymal stem cells will be infused at day 0, day 3 and day 5 (+/- 1 day), in patients with moderate to severe ARDS with a mechanical ventilation. day 0: 1.10^6 MSC/kg day 3: 0.5. 10^6 MSC/kg day 5: 0.5 . 10^6 MSC/kg
Only the vehicle solution, without MSCs, containing albumin 4% , NaCl 0,9% and ACD will be injected to patients at day 0, 3 and 5 (+/-1 day).
Outcomes
Primary Outcome Measures
PaO2 / FiO2 ratio
The primary endpoint is the percentage of patients with a PaO2/FiO2 ratio > 200 at D10 of treatment with MSC-GW or placebo.
Secondary Outcome Measures
respiratory function evolution
The evolution of the PaO2/FiO2 ratio between Day 0 (or Day 1) and Day 14 of treatment with MSC-GW or placebo is a secondary endpoint.
respiratory assistance
The effect of WJ-MSC on respiratory assistance is evaluated by the proportion of days without invasive respiratory assistance during the hospital stay and maximum on Day 28 (number of days without invasive respiratory assistance / number of hospital days fixed at day 28)
organ failures 1
Difference in sequential organ failure assessment score (SOFA score), grading 0 (best) to 4 (worst), between Day 5-Day 0 and D14-Day 0
organ failures 2
number of days without extra-renal treatment / number of hospital days fixed at day 28
organ failures 3
number of days without vasopressor support
duration of intensive care
The duration of stay in intensive care unit
Cause of death
Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90
respiratory morbidity (TDM, functional respiratory measures)
respiratory morbidity on Day 90
viral load
The evolution of the viral load is evaluated by RT PCR SARS-Cov-2 monitoring on a nasopharyngeal swab (or any other sample) at diagnosis, at Day 7, Day 14, Day 21, Day 28 or on the last day of hospitalisation
Anti-HLA antibody rate
- The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90
immediate hypersensitivity reactions
The occurrence of immediate hypersensitivity reactions (chills, hyperthermia associated with hypotension) within 4 to 6 hours of the WJ MSC or placebo infusion.
thromboembolic adverse events 1
The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)
thromboembolic adverse events 2
daily monitoring of transthoracic echocardiography
infectious adverse events
blood cultures in case of T° > 38,5°C
Full Information
NCT ID
NCT04625738
First Posted
November 4, 2020
Last Updated
October 28, 2021
Sponsor
Central Hospital, Nancy, France
1. Study Identification
Unique Protocol Identification Number
NCT04625738
Brief Title
Efficacy of Infusions of MSC From Wharton Jelly in the SARS-Cov-2 (COVID-19) Related Acute Respiratory Distress Syndrome
Acronym
MSC-COVID19
Official Title
Efficacy of Infusions of Mesenchymal Stem Cells From Wharton Jelly in the Moderate to Severe SARS-Cov-2 Related Acute Respiratory Distress Syndrome (COVID-19): A Phase IIa Double-blind Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
November 6, 2020 (Actual)
Primary Completion Date
May 14, 2021 (Actual)
Study Completion Date
September 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central Hospital, Nancy, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Mesenchymal stem cells (MSCs) are of potential help in acute respiratory distress syndrome (ARDS), due to their anti-inflammatory properties.
The investigators will analyze the effect of 3 iterative infusions of ex vivo expanded Wharton's Jelly MSCs (total dose 2.10^6/kg) in patients with ARDS due to COVID19, who require mechanical ventilation.
Detailed Description
This study is designed to analyze the impact of Wharton's Jelly Mesenchymal Stem Cells on moderate to severe ARDS due to COVID19 in adult patients who require mechanical ventilation. It is a Phase IIa double-blind randomized controlled trial.
30 patients are planned.
Patients will be randomized and will receive, with the conventional treatment recommended to treat ARDS:
Either Wharton's Jelly MSCs in a solution of albumin 4% (40% of final volume), NaCl 0,9% (50% of the final volume) et ACD formule A (10% of the final volume) . Treatment will be administered intravenously during 10 minutes following that scheme:
Day 0 (or 1): 1. 10^6 MSC/kg (maximum 80.10^6 MSC)
Day 3 (or 4): 0.5 . 10^6 MSC/kg (maximum 40. 10^6 MSC)
Day 5 (or 6): 0.5 . 10^6 MSC/kg (maximum 40. 10^6 MSC) An interval of 2 days will be respected between 2 infusions.
Either a placebo, which contains the same solution of albumin, NaCl 0.9% and ACD without cells. The volume will be of 75 ml, infused in 10 minutes.
The main objective is to investigate efficacy of WJ-MSCs, compared to a placebo, on respiratory function evolution during the first 14 days of study treatment in patients with SARS-CoV-2 related moderate to severe ARDS.
Secondary objectives are to assess the effect of WJ-MSC, compared to placebo, in patients with SARS-CoV-2 related moderate to severe ARDS, on:
the duration of invasive mechanical ventilation during the hospital stay and maximum for 28 days
the evolution of organ failures during the hospital stay and maximum for 28 days
the duration of stay in intensive care unit, the mortality during intensive care unit, during hospitalization, on D28 and D90, and the respiratory morbidity.
the evolution of viral load between D0 and D28
the immediate or delayed tolerance following the WJ-MSCs injection
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19 ARDS
Keywords
COVID, ARDS, MSC, mesenchymal stem cells, Wharton's Jelly, inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase IIa double-blind randomized controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MSC Arm
Arm Type
Experimental
Arm Description
Ex vivo expanded Wharton's Jelly derived mesenchymal stem cells will be infused at day 0, day 3 and day 5 (+/- 1 day), in patients with moderate to severe ARDS with a mechanical ventilation.
day 0: 1.10^6 MSC/kg day 3: 0.5. 10^6 MSC/kg day 5: 0.5 . 10^6 MSC/kg
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Only the vehicle solution, without MSCs, containing albumin 4% , NaCl 0,9% and ACD will be injected to patients at day 0, 3 and 5 (+/-1 day).
Intervention Type
Biological
Intervention Name(s)
Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
Intervention Description
Ex vivo expanded Wharton's Jelly derived mesenchymal stem cells will be infused at day 0, day 3 and day 5 (+/- 1 day), in patients with moderate to severe ARDS with a mechanical ventilation.
day 0: 1.10^6 MSC/kg day 3: 0.5. 10^6 MSC/kg day 5: 0.5 . 10^6 MSC/kg
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Only the vehicle solution, without MSCs, containing albumin 4% , NaCl 0,9% and ACD will be injected to patients at day 0, 3 and 5 (+/-1 day).
Primary Outcome Measure Information:
Title
PaO2 / FiO2 ratio
Description
The primary endpoint is the percentage of patients with a PaO2/FiO2 ratio > 200 at D10 of treatment with MSC-GW or placebo.
Time Frame
day 10
Secondary Outcome Measure Information:
Title
respiratory function evolution
Description
The evolution of the PaO2/FiO2 ratio between Day 0 (or Day 1) and Day 14 of treatment with MSC-GW or placebo is a secondary endpoint.
Time Frame
between Day 0 (or Day 1) and Day 14 of treatment
Title
respiratory assistance
Description
The effect of WJ-MSC on respiratory assistance is evaluated by the proportion of days without invasive respiratory assistance during the hospital stay and maximum on Day 28 (number of days without invasive respiratory assistance / number of hospital days fixed at day 28)
Time Frame
between day 0 (or 1) and day 28 (or last day of hospitalization if before day 28)
Title
organ failures 1
Description
Difference in sequential organ failure assessment score (SOFA score), grading 0 (best) to 4 (worst), between Day 5-Day 0 and D14-Day 0
Time Frame
Day 0 to day 14
Title
organ failures 2
Description
number of days without extra-renal treatment / number of hospital days fixed at day 28
Time Frame
day 0 to day 28
Title
organ failures 3
Description
number of days without vasopressor support
Time Frame
day 0 to day 28
Title
duration of intensive care
Description
The duration of stay in intensive care unit
Time Frame
day 0 to 90
Title
Cause of death
Description
Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90
Time Frame
day 0 to 90
Title
respiratory morbidity (TDM, functional respiratory measures)
Description
respiratory morbidity on Day 90
Time Frame
day 90
Title
viral load
Description
The evolution of the viral load is evaluated by RT PCR SARS-Cov-2 monitoring on a nasopharyngeal swab (or any other sample) at diagnosis, at Day 7, Day 14, Day 21, Day 28 or on the last day of hospitalisation
Time Frame
day 0 to day 28 (or last day of hospitalization if before day 28)
Title
Anti-HLA antibody rate
Description
- The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90
Time Frame
day 0 to day 90
Title
immediate hypersensitivity reactions
Description
The occurrence of immediate hypersensitivity reactions (chills, hyperthermia associated with hypotension) within 4 to 6 hours of the WJ MSC or placebo infusion.
Time Frame
day 0, day 3, day 5 (+/- 1day)
Title
thromboembolic adverse events 1
Description
The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)
Time Frame
day 0 to day 14
Title
thromboembolic adverse events 2
Description
daily monitoring of transthoracic echocardiography
Time Frame
day 0 to day 14
Title
infectious adverse events
Description
blood cultures in case of T° > 38,5°C
Time Frame
day 0 to day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Man or woman 18 years of age or older
Patient with a biologically confirmed SARS-CoV-2 infection (by positive RT-PCR on a nasopharyngeal sample or any other sample)
Patient with moderate to severe ARDS according to the BERLIN definition defined by a PaO2 / FiO2 ratio <200 and with endotracheal intubation and under invasive mechanical ventilation
Patient hospitalized in the intensive care unit
Provision of a written informed consent to participate to the study or for whom the consent of a family member or support person has been obtained (if the patient is unable to give consent) or inclusion in an immediate vital emergency if applicable
Any woman of childbearing age with a negative Beta HCG test
Social Security affiliation
Exclusion Criteria:
Patient under invasive mechanical ventilation for more than 48 hours
Patient with a chronic respiratory disease under oxygen therapy
Patients with a history of Class III or IV pulmonary arterial hypertension (WHO classification)
Patients under ECMO
Immunosuppressive therapy (including corticosteroid therapy> 20 mg prednisolone)
Active solid tumor or in remission for less than 2 years, malignant hematological disease, asplenia
Patient who has received a hematopoietic stem transplantation or an organ transplant
Therapeutic limitations like progression to expected death within 24 hours (according to the opinion of the medical team)
Hypersensitivity to albumin or to any of the excipients (caprylic acid or sodium caprylate)
Patient included in another ongoing interventional therapeutic trial
Pregnant woman, parturient, nursing mother
Minor (not emancipated)
Person without liberty by judiciary or administrative decision
Person undergoing psychiatric care under Articles L. 3212-1 and L. 3213-1 which do not fall under the provisions of Article L. 1121-8 (hospitalization without consent).
Adult over 18 who are under a legal protection measure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoine KIMMOUN, MD, PhD
Organizational Affiliation
Central Hospital, Nancy, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sébastien GIBOT, MD, PhD
Organizational Affiliation
Central Hospital, Nancy, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nancy University Hospital
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54500
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Infusions of MSC From Wharton Jelly in the SARS-Cov-2 (COVID-19) Related Acute Respiratory Distress Syndrome
We'll reach out to this number within 24 hrs