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Efficacy of Infusions of MSC From Wharton Jelly in the SARS-Cov-2 (COVID-19) Related Acute Respiratory Distress Syndrome (MSC-COVID19)

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ClinicalTrials.gov Identifier: NCT04625738
Recruitment Status : Completed
First Posted : November 12, 2020
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
POCHON Cécile, Central Hospital, Nancy, France

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.


Condition or disease Intervention/treatment Phase
COVID19 ARDS Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells Biological: Placebo Phase 2

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:

  1. the duration of invasive mechanical ventilation during the hospital stay and maximum for 28 days
  2. the evolution of organ failures during the hospital stay and maximum for 28 days
  3. the duration of stay in intensive care unit, the mortality during intensive care unit, during hospitalization, on D28 and D90, and the respiratory morbidity.
  4. the evolution of viral load between D0 and D28
  5. the immediate or delayed tolerance following the WJ-MSCs injection

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase IIa double-blind randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2020
Actual Primary Completion Date : May 14, 2021
Actual Study Completion Date : September 1, 2021


Arm Intervention/treatment
Experimental: MSC Arm

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

Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells

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


Placebo Comparator: Placebo Arm
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).
Biological: Placebo
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 Measures :
  1. PaO2 / FiO2 ratio [ Time Frame: day 10 ]
    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 :
  1. respiratory function evolution [ Time Frame: between Day 0 (or Day 1) and Day 14 of treatment ]
    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.

  2. respiratory assistance [ Time Frame: between day 0 (or 1) and day 28 (or last day of hospitalization if before day 28) ]
    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)

  3. organ failures 1 [ Time Frame: Day 0 to day 14 ]
    Difference in sequential organ failure assessment score (SOFA score), grading 0 (best) to 4 (worst), between Day 5-Day 0 and D14-Day 0

  4. organ failures 2 [ Time Frame: day 0 to day 28 ]
    number of days without extra-renal treatment / number of hospital days fixed at day 28

  5. organ failures 3 [ Time Frame: day 0 to day 28 ]
    number of days without vasopressor support

  6. duration of intensive care [ Time Frame: day 0 to 90 ]
    The duration of stay in intensive care unit

  7. Cause of death [ Time Frame: day 0 to 90 ]
    Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90

  8. respiratory morbidity (TDM, functional respiratory measures) [ Time Frame: day 90 ]
    respiratory morbidity on Day 90

  9. viral load [ Time Frame: day 0 to day 28 (or last day of hospitalization if before day 28) ]
    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

  10. Anti-HLA antibody rate [ Time Frame: day 0 to day 90 ]
    - The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90

  11. immediate hypersensitivity reactions [ Time Frame: day 0, day 3, day 5 (+/- 1day) ]
    The occurrence of immediate hypersensitivity reactions (chills, hyperthermia associated with hypotension) within 4 to 6 hours of the WJ MSC or placebo infusion.

  12. thromboembolic adverse events 1 [ Time Frame: day 0 to day 14 ]
    The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)

  13. thromboembolic adverse events 2 [ Time Frame: day 0 to day 14 ]
    daily monitoring of transthoracic echocardiography

  14. infectious adverse events [ Time Frame: day 0 to day 14 ]
    blood cultures in case of T° > 38,5°C



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Man or woman 18 years of age or older
  2. Patient with a biologically confirmed SARS-CoV-2 infection (by positive RT-PCR on a nasopharyngeal sample or any other sample)
  3. 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
  4. Patient hospitalized in the intensive care unit
  5. 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
  6. Any woman of childbearing age with a negative Beta HCG test
  7. Social Security affiliation

Exclusion Criteria:

  1. Patient under invasive mechanical ventilation for more than 48 hours
  2. Patient with a chronic respiratory disease under oxygen therapy
  3. Patients with a history of Class III or IV pulmonary arterial hypertension (WHO classification)
  4. Patients under ECMO
  5. Immunosuppressive therapy (including corticosteroid therapy> 20 mg prednisolone)
  6. Active solid tumor or in remission for less than 2 years, malignant hematological disease, asplenia
  7. Patient who has received a hematopoietic stem transplantation or an organ transplant
  8. Therapeutic limitations like progression to expected death within 24 hours (according to the opinion of the medical team)
  9. Hypersensitivity to albumin or to any of the excipients (caprylic acid or sodium caprylate)
  10. Patient included in another ongoing interventional therapeutic trial
  11. Pregnant woman, parturient, nursing mother
  12. Minor (not emancipated)
  13. Person without liberty by judiciary or administrative decision
  14. 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).
  15. Adult over 18 who are under a legal protection measure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04625738


Locations
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France
Nancy University Hospital
Vandœuvre-lès-Nancy, France, 54500
Sponsors and Collaborators
Central Hospital, Nancy, France
Investigators
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Principal Investigator: Antoine KIMMOUN, MD, PhD Central Hospital, Nancy, France
Principal Investigator: Sébastien GIBOT, MD, PhD Central Hospital, Nancy, France
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Responsible Party: POCHON Cécile, Coordinator, Central Hospital, Nancy, France
ClinicalTrials.gov Identifier: NCT04625738    
Other Study ID Numbers: 2020-002772-12
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: November 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by POCHON Cécile, Central Hospital, Nancy, France:
COVID
ARDS
MSC
mesenchymal stem cells
Wharton's Jelly
inflammation
Additional relevant MeSH terms:
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COVID-19
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury