COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.
The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has unprecedentedly spread in the worldwide and been declared as a pandemic by the world health organization. COVID-19 is characterized by sustained cytokines production and hyper-inflammation, can cause clusters of severe respiratory illness with a fatality rate around 2-5%. There are currently no prophylactic vaccine and no specific antiviral treatment agents available recommended for COVID-19. Therefore, it is urgent to find a safe and effective therapeutic approach to COVID-19. During the last decade, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. These findings seem to highlight that the beneficial effect of MSC-based treatment could be principally due by the immunomodulation and regenerative potential of these cells. MSCs could significantly reduce the pathological changes of lung and inhibit the cell-mediated immune inflammatory response induced by influenza virus in animal model . MSCs has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. Our phase I preliminary data of parallel assignment study(NCT04252118) showed that three doses of MSCs was safe in patients with COVID-19. Randomized control trial is needed to assess efficacy and safety. The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 90 severe COVID-19 patients will be recruited in China. 60 patients will receive i.v. transfusion 3 times of MSCs (4.0\*10E7 cells per time) and the standard of care as the treated group. In addition, the 30 patients will receive placebo and standard of care as control group. Change in lesion proportion (%) of full lung volume from baseline to day 10, day28 and 90, change in consolidation/ ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90, time to clinical improvement in 28 days, mMRC (Modified Medical Research Council) dyspnea scale, 6-minute walk test, maximum vital capacity (VCmax), Diffusing Capacity (DLCO), oxygen saturation, oxygenation index, duration of oxygen therapy, side effects, immunological characteristics (immune cells, inflammatory factors, etc.) will be evaluated during the 90 days follow up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
100
3 does of UC-MSCs(4.0\*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
3 does of placebo（intravenously at Day 0, Day 3, Day 6）
General Hospital of Central Theater Command
Wuhan, Hubei, China
Maternal and Child Hospital of Hubei Province
Wuhan, Hubei, China
Wuhan Huoshenshan Hospital
Wuhan, Hubei, China
Change in lesion proportion (%) of full lung volume from baseline to day 28.
Evaluation of Pneumonia Improvement
Time frame: Day 28
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
Evaluation of Pneumonia Improvement
Time frame: Day 10, Day 90
Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Evaluation of Pneumonia Improvement
Time frame: Day 10, Day 28, Day 90
Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Evaluation of Pneumonia Improvement
Time frame: Day 10, Day 28, Day 90
Pulmonary fibrosis - related morphological features in CT scan at day 90 a. cord-like shadow b. honeycomb-like shadows c. interlobular septal thickening d. intralobular interstitial thickening e. pleural thickening
Evaluation of Pneumonia Improvement
Time frame: Day 90
Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
Evaluation of Pneumonia Improvement
Time frame: Day 10, Day 28, Day 90
Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.
Evaluation of Pneumonia Improvement
Time frame: Day 10, Day 28, Day 90
Time to clinical improvement in 28 days.
Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale: 1. Not hospitalized; 2. Hospitalized, not requiring supplemental oxygen; 3. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5. Hospitalized, on invasive mechanical ventilation or ECMO; 6. Death.
Time frame: Day 28
Oxygenation index( PaO2/FiO2)
Evaluation of Pneumonia Improvement
Time frame: Day 6, Day 10, Day 28
Duration of oxygen therapy(days)
Evaluation of Pneumonia Improvement
Time frame: Day 28, Day 90
Blood oxygen saturation
Evaluation of Pneumonia Improvement
Time frame: Day 6, Day 10, Day 28
6-minute walk test
Evaluation of Pneumonia Improvement
Time frame: Day 28, Day 90
Maximum vital capacity (VCmax)
Evaluation of Pneumonia Improvement
Time frame: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Diffusing Capacity (DLCO)
Evaluation of Pneumonia Improvement
Time frame: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
mMRC (Modified Medical Research Council) dyspnea scale
Evaluation of Pneumonia Improvement No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.
Time frame: Day 28, Day 90
Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
Marker of Immunological function
Time frame: Day 6, Day 10, Day 28, Day 90
Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
Marker of Immunological function
Time frame: Day 6, Day 10, Day 28, Day 90
Adverse events
Safety endpoints
Time frame: Day 0 through Day 90
Serious adverse events
Safety endpoints
Time frame: Day 0 through Day 90
All-cause mortality
Safety endpoints
Time frame: Day 0 through Day 90
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.