Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS (STROMA-CoV2)
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|ClinicalTrials.gov Identifier: NCT04333368|
Recruitment Status : Active, not recruiting
First Posted : April 3, 2020
Last Update Posted : December 4, 2020
Whereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment.
Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record.
The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care.
The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.
|Condition or disease||Intervention/treatment||Phase|
|Severe Acute Respiratory Syndrome Coronavirus 2 Severe Acute Respiratory Distress Syndrome||Biological: Umbilical cord Wharton's jelly-derived human Other: NaCl 0.9%||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||47 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS|
|Actual Study Start Date :||April 6, 2020|
|Estimated Primary Completion Date :||January 30, 2021|
|Estimated Study Completion Date :||April 6, 2022|
Biological: Umbilical cord Wharton's jelly-derived human
Umbilical cord Wharton's jelly-derived human MSC (at the dose of 1 Million / kg) will be administered via a peripheral or central venous line over 60 minutes, using tubing with a 200-μm filter. Cells, in a 150 mL volume, will be delivered at D1 - D3 - D5.
|Placebo Comparator: NaCl||
Other: NaCl 0.9%
NaCl 0.9% (150 mL) given via an intravenous route at D1 - D3 - D5
- Respiratory efficacy evaluated by the increase in PaO2/FiO2 ratio from baseline to day 7 in the experimental group compared with the placebo group [ Time Frame: From baseline to day 7 ]
- Lung injury score [ Time Frame: From baseline to day 28 ]
- Oxygenation index [ Time Frame: From baseline to day 28 ]
- In-hospital mortality [ Time Frame: From baseline to day 28 ]
- Mortality [ Time Frame: At day 28 ]
- Ventilator-free days [ Time Frame: From baseline to day 28 ]
- Number of days between randomization and the first day the patient meets weaning criteria o Number of days between randomization and the first day the patient meets PaO2/FiO2 > 200 (out of a prone positioning session) [ Time Frame: From baseline to day 28 ]
- Cumulative use of sedatives [ Time Frame: From baseline to day 28 ]
- Cumulative duration of use of sedatives [ Time Frame: From baseline to day 28 ]
- Cumulative duration of use of neuromuscular blocking agents (other than used for intubation) [ Time Frame: From baseline to day 28 ]
- Cumulative use of neuromuscular blocking agents (other than used for intubation) [ Time Frame: From baseline to day 28 ]
- ICU-acquired weakness and delirium [ Time Frame: From baseline to day 28 ]
- Treatment-induced toxicity rate and adverse events up to day 28 [ Time Frame: From baseline to day 28 ]
- Quality of life at one year (EQ5D-3L quality of life questionnaire) [ Time Frame: At 6 months and 12 months ]
- Measurements of plasmatic cytokines (IL1, IL6, IL8, TNF-alpha, IL10, TGF-beta, sRAGE, Ang2) level [ Time Frame: At day 1, 3, 5, 7 and 14 ]
- Anti-HLA antibodies plasmatic dosage [ Time Frame: From baseline to day 14, and at 6 months ]
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): NCT04333368
|Hôpital Pitié-Salpêtrière - APHP|
|Paris, France, 75013|
|Hôpital Européen Georges Pompidou - APHP|
|Paris, France, 75015|
|Principal Investigator:||Antoine MONSEL, MD, PhD||Hôpital Pitié-Salpêtrière - Assitance Publique - Hôpitaux de Paris|