Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)
Condition: Corona Virus Disease 2019(COVID-19)
MeSH terms: COVID-19; Virus Diseases; Coronavirus Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): UC-MSCs; Saline containing 1% Human serum albumin（solution without UC-MSCs）
Intervention type(s): Biological; Biological
Intervention description(s): 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）
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, placebo-controlled study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment