Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)

18. august 2020 opdateret af: Fu-Sheng Wang, Beijing 302 Hospital

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

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

100

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Kina
    • Hubei
      • Wuhan, Hubei, Kina, 430000
        • General Hospital of Central Theater Command
      • Wuhan, Hubei, Kina, 430000
        • Maternal and Child Hospital of Hubei Province
      • Wuhan, Hubei, Kina, 430000
        • Wuhan Huoshenshan Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Male or female, aged at 18 years (including) -75 years old
  2. Hospitalized
  3. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source
  4. Pneumonia that is judged by computed tomography
  5. 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
  6. Interstitial lung damage is judged by computed tomography.

Exclusion Criteria:

  1. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;
  2. Patients with malignant tumor, other serious systemic diseases and psychosis;
  3. Patients who are participating in other clinical trials;
  4. Inability to provide informed consent or to comply with test requirements.
  5. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
  6. Invasive ventilation
  7. Shock
  8. Combined with other organ failure( need organ support)
  9. Interstitial lung damage caused by other reasons ( in 2 weeks)
  10. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
Biologisk: UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
Placebo komparator: Placebo
Participants will receive standard of care plus 3 does of placebo
Biologisk: Saline containing 1% Human serum albumin（solution without UC-MSCs）
3 does of placebo（intravenously at Day 0, Day 3, Day 6）

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in lesion proportion (%) of full lung volume from baseline to day 28.
Tidsramme: Day 28
Evaluation of Pneumonia Improvement
Day 28

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
Tidsramme: Day 10, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 90
Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Tidsramme: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
Tidsramme: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
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
Tidsramme: Day 90
Evaluation of Pneumonia Improvement
Day 90
Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
Tidsramme: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
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.
Tidsramme: Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Time to clinical improvement in 28 days.
Tidsramme: Day 28

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.
Day 28
Oxygenation index( PaO2/FiO2)
Tidsramme: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
Duration of oxygen therapy(days)
Tidsramme: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Blood oxygen saturation
Tidsramme: Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
6-minute walk test
Tidsramme: Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Maximum vital capacity (VCmax)
Tidsramme: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Diffusing Capacity (DLCO)
Tidsramme: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
mMRC (Modified Medical Research Council) dyspnea scale
Tidsramme: Day 28, Day 90

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
Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
Tidsramme: Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
Tidsramme: Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Adverse events
Tidsramme: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
Serious adverse events
Tidsramme: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
All-cause mortality
Tidsramme: Day 0 through Day 90
Safety endpoints
Day 0 through Day 90

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Beijing 302 Hospital

Samarbejdspartnere

Maternal and Child Health Hospital of Hubei Province
Huoshenshan Hospital
VCANBIO Cell & Gene Engineering Corporation, Ltd
The General Hospital of Central Theater Command

Efterforskere

  • Studiestol: Fu-Sheng Wang, MD, PhD, Beijing 302 Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

5. marts 2020

Primær færdiggørelse (Faktiske)

12. maj 2020

Studieafslutning (Faktiske)

9. juli 2020

Datoer for studieregistrering

Først indsendt

24. februar 2020

Først indsendt, der opfyldte QC-kriterier

25. februar 2020

Først opslået (Faktiske)

28. februar 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

19. august 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. august 2020

Sidst verificeret

1. august 2020

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2020-013-D

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Corona Virus sygdom 2019 (COVID-19)

Kliniske forsøg med UC-MSCs

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Malaysia

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

3
Abonner