COVID19 ARDSPhase 2MSC-COVID19NCT04625738

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

A Phase 2 study testing Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells in people with COVID19 ARDS, run by Central Hospital, Nancy, France at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: COVID19 ARDS
What is being tested?: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 30 participants
Where: 1 siteFrance
Study dates: 6 Nov 2020to 1 Sep 2021
Phase: Phase 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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 15Show fewer

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

Trial locations and contacts

1 site in 1 country.

France1 site

Nancy University Hospital
Vandœuvre-lès-Nancy, 54500

Other trials in France

About this study

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

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.

Read the 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

Conditions: COVID19 ARDS
Being tested: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells, Placebo
Keywords: COVID, ARDS, MSC, mesenchymal stem cells, Wharton's Jelly, inflammation
Medical subject headings: Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ex vivo expanded Wharton's Jelly Mesenchymal Stem CellsBiological
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
PlaceboBiological
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).

Study groups in NCT04625738
Study group	Role	What they receive
MSC Arm	Experimental	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 Receives: Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
Placebo Arm	Placebo comparator	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). Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: day 10

Secondary outcomes (14)

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.
Measured: between Day 0 (or Day 1) and Day 14 of treatment
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)
Measured: between day 0 (or 1) and day 28 (or last day of hospitalization if before 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
Measured: Day 0 to day 14
organ failures 2
number of days without extra-renal treatment / number of hospital days fixed at day 28
Measured: day 0 to day 28
organ failures 3
number of days without vasopressor support
Measured: day 0 to day 28
duration of intensive care
The duration of stay in intensive care unit
Measured: day 0 to 90
Cause of death
Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90
Measured: day 0 to 90
respiratory morbidity (TDM, functional respiratory measures)
respiratory morbidity on Day 90
Measured: 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
Measured: day 0 to day 28 (or last day of hospitalization if before day 28)
Anti-HLA antibody rate
- The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90
Measured: day 0 to 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.
Measured: day 0, day 3, day 5 (+/- 1day)
thromboembolic adverse events 1
The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)
Measured: day 0 to day 14
thromboembolic adverse events 2
daily monitoring of transthoracic echocardiography
Measured: day 0 to day 14
infectious adverse events
blood cultures in case of T° > 38,5°C
Measured: day 0 to day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Nov 20201 Sep 2021

First posted12 Nov 2020
Study start6 Nov 2020
Primary completion14 May 2021
Study completion1 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for COVID19 ARDSStudies of the same condition, open and under way.
More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Phase IIa double-blind randomized controlled trial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04625738
Sponsor's protocol ID: 2020-002772-12
Acronym: MSC-COVID19
Status last verified: Oct 2021
First submitted: 4 Nov 2020
Last updated: 5 Nov 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Pochon C, Laroye C, Kimmoun A, Reppel L, Dhuyser A, Rousseau H, Gauthier M, Petitpain N, Chabot JF, Valentin S, de Carvalho Bittencourt M, Peres M, Aarnink A, Decot V, Bensoussan D, Gibot S. Efficacy of Wharton Jelly Mesenchymal Stromal Cells infusions in moderate to severe SARS-Cov-2 related acute respiratory distress syndrome: a phase 2a double-blind randomized controlled trial. Front Med (Lausanne). 2023 Aug 29;10:1224865. doi: 10.3389/fmed.2023.1224865. eCollection 2023.
PubMed 37706025

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All COVID19 ARDS trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04625738
Acronym / sponsor ID: MSC-COVID19 / 2020-002772-12
Conditions: COVID19 ARDS
Keywords: COVID, ARDS, MSC, mesenchymal stem cells, Wharton's Jelly, inflammation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Central Hospital, Nancy, FranceUniversity, hospital or other
Study start: 6 Nov 2020 (actual)
Primary completion: 14 May 2021 (actual)
Study completion: 1 Sep 2021 (actual)
First posted: 12 Nov 2020 (actual)
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.

Mesenchymal stem cells (MSCs) are of potential help in acute respiratory distress syndrome (ARDS), due to their anti-inflammatory properties.

Detailed description

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.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Phase IIa double-blind randomized controlled trial

Arm	Type	Receives
MSC Arm	Experimental	Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem CellsEx 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 Arm	Placebo comparator	Biological: PlaceboOnly 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (15 listed)

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)

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
Ex vivo expanded Wharton's Jelly Mesenchymal Stem CellsEx 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	MSC Arm
PlaceboOnly 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 Arm

Primary outcome

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.

14 secondary outcomes

respiratory function evolution
Time frame: between Day 0 (or Day 1) and Day 14 of treatment
respiratory assistance
Time frame: between day 0 (or 1) and day 28 (or last day of hospitalization if before day 28)
organ failures 1
Time frame: Day 0 to day 14
organ failures 2
Time frame: day 0 to day 28
organ failures 3
Time frame: day 0 to day 28
duration of intensive care
Time frame: day 0 to 90
Cause of death
Time frame: day 0 to 90
respiratory morbidity (TDM, functional respiratory measures)
Time frame: day 90
viral load
Time frame: day 0 to day 28 (or last day of hospitalization if before day 28)
Anti-HLA antibody rate
Time frame: day 0 to day 90
immediate hypersensitivity reactions
Time frame: day 0, day 3, day 5 (+/- 1day)
thromboembolic adverse events 1
Time frame: day 0 to day 14
thromboembolic adverse events 2
Time frame: day 0 to day 14
infectious adverse events
Time frame: day 0 to day 14

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
Derived from this study: PubMed 37706025Pochon C, Laroye C, Kimmoun A, Reppel L, Dhuyser A, Rousseau H, Gauthier M, Petitpain N, Chabot JF, Valentin S, de Carvalho Bittencourt M, Peres M, Aarnink A, Decot V, Bensoussan D, Gibot S. Efficacy of Wharton Jelly Mesenchymal Stromal Cells infusions in moderate to severe SARS-Cov-2 related acute respiratory distress syndrome: a phase 2a double-blind randomized controlled trial. Front Med (Lausanne). 2023 Aug 29;10:1224865. doi: 10.3389/fmed.2023.1224865. eCollection 2023.
Individual participant dataSharing planned: No

Related trials for COVID19 ARDS

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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.

Antoine KIMMOUN, MD, PhD principal investigator

Central Hospital, Nancy, France

Sébastien GIBOT, MD, PhD principal investigator

Central Hospital, Nancy, France

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells in people with COVID19 ARDS, run by Central Hospital, Nancy, France at 1 site in France.

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 7 inclusion and 15 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: finished, as of the sponsor's last update on 5 Nov 2021. 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 France. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PaO2 / FiO2 ratio (time frame: day 10). 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 NCT04625738, which also lists 1 linked publication.

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 5 Nov 2021.