Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)
A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Hubei
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Wuhan, Hubei, China, 430000
- General Hospital of Central Theater Command
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Wuhan, Hubei, China, 430000
- Maternal and Child Hospital of Hubei Province
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Wuhan, Hubei, China, 430000
- Wuhan Huoshenshan Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Male or female, aged at 18 years (including) -75 years old
- Hospitalized
- Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source
- Pneumonia that is judged by computed tomography
- In accordance with any one of the following : 1)dyspnea (RR ≥ 30 times / min), 2)finger oxygen saturation ≤ 93% in resting state, 3)arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG, 4)pulmonary imaging shows that the focus progress > 50% in 24-48 hours
- Interstitial lung damage is judged by computed tomography.
Exclusion Criteria:
- Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;
- Patients with malignant tumor, other serious systemic diseases and psychosis;
- Patients who are participating in other clinical trials;
- Inability to provide informed consent or to comply with test requirements.
- Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
- Invasive ventilation
- Shock
- Combined with other organ failure( need organ support)
- Interstitial lung damage caused by other reasons ( in 2 weeks)
- The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
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3 does of UC-MSCs(4.0*10E7
cells per time) intravenously at Day 0, Day 3, Day 6.
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Comparador de Placebo: Placebo
Participants will receive standard of care plus 3 does of placebo
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3 does of placebo（intravenously at Day 0, Day 3, Day 6）
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in lesion proportion (%) of full lung volume from baseline to day 28.
Prazo: Day 28
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Evaluation of Pneumonia Improvement
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Day 28
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
Prazo: Day 10, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 90
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Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Prazo: Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Prazo: Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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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
Prazo: Day 90
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Evaluation of Pneumonia Improvement
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Day 90
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Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
Prazo: Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.
Prazo: Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Time to clinical improvement in 28 days.
Prazo: Day 28
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Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale:
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Day 28
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Oxygenation index( PaO2/FiO2)
Prazo: Day 6, Day 10, Day 28
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Evaluation of Pneumonia Improvement
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Day 6, Day 10, Day 28
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Duration of oxygen therapy(days)
Prazo: Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 28, Day 90
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Blood oxygen saturation
Prazo: Day 6, Day 10, Day 28
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Evaluation of Pneumonia Improvement
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Day 6, Day 10, Day 28
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6-minute walk test
Prazo: Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 28, Day 90
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Maximum vital capacity (VCmax)
Prazo: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Diffusing Capacity (DLCO)
Prazo: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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mMRC (Modified Medical Research Council) dyspnea scale
Prazo: Day 28, Day 90
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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. |
Day 28, Day 90
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Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
Prazo: Day 6, Day 10, Day 28, Day 90
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Marker of Immunological function
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Day 6, Day 10, Day 28, Day 90
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Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
Prazo: Day 6, Day 10, Day 28, Day 90
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Marker of Immunological function
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Day 6, Day 10, Day 28, Day 90
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Adverse events
Prazo: Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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Serious adverse events
Prazo: Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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All-cause mortality
Prazo: Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: Fu-Sheng Wang, MD, PhD, Beijing 302 Hospital
Publicações e links úteis
Publicações Gerais
- Shi L, Yuan X, Yao W, Wang S, Zhang C, Zhang B, Song J, Huang L, Xu Z, Fu JL, Li Y, Xu R, Li TT, Dong J, Cai J, Li G, Xie Y, Shi M, Li Y, Zhang Y, Xie WF, Wang FS. Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial. EBioMedicine. 2022 Jan;75:103789. doi: 10.1016/j.ebiom.2021.103789. Epub 2021 Dec 25.
- Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, Wang S, Zhang C, Yuan X, Xu Z, Huang L, Fu JL, Li Y, Zhang Y, Yao WQ, Liu T, Song J, Sun L, Yang F, Zhang X, Zhang B, Shi M, Meng F, Song Y, Yu Y, Wen J, Li Q, Mao Q, Maeurer M, Zumla A, Yao C, Xie WF, Wang FS. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021 Feb 10;6(1):58. doi: 10.1038/s41392-021-00488-5.
Datas de registro do estudo
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Conclusão Primária (Real)
Conclusão do estudo (Real)
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Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
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Outros números de identificação do estudo
- 2020-013-D
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