Last reviewed · How we verify

NCT04355728

Use of UC-MSCs for COVID-19 Patients

Completed Phase 1, PHASE2 Results posted Last updated 6 December 2021
What this trial tests

Phase 1, PHASE2 trial testing Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. in Corona Virus Infection in 24 participants. Completed in 31 October 2020.

Timeline
25 April 2020
Primary endpoint
31 October 2020
31 October 2020

Quick facts

Lead sponsorCamillo Ricordi
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment24
Start date25 April 2020
Primary completion31 October 2020
Estimated completion31 October 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Camillo Ricordi — full company profile →

Who can join

18 and older, any sex, with Corona Virus Infection or ARDS. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Pre-Specified Infusion Associated Adverse Events Primary · 6 and 24 hours

Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion: 1. An increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg/min * Phenylephrine: 100 μg/min * Dopamine: 10 μg/kg/min * Epinephrine: 10 μg/min 2. In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of \>20%. 3. In patients receiving high fl

Number of subjects with an increase in vasopressor dose at 6 h
GroupValue95% CI
UC-MSCs Group1
Control Group1
In subjects receiving mechanical ventilation, Number of subjects with worsening of hypoxemia at 6 h
GroupValue95% CI
UC-MSCs Group1
Control Group1
In subjects on high flow oxygen therapy:worsening hypoxemia(req intubat, mechanical ventilat) at 6 h
GroupValue95% CI
UC-MSCs Group0
Control Group0
Number of subjects with new cardiac arrhythmia requiring cardioversion at 6 h
GroupValue95% CI
UC-MSCs Group0
Control Group1
Number of subjects with new ventricular tachycardia, ventricular fibrillation, or asystole at 6 h
GroupValue95% CI
UC-MSCs Group0
Control Group1
A clinical scenario consistent with transfusion incompatibility or transfusion-rel infection at 6h
GroupValue95% CI
UC-MSCs Group0
Control Group0
Number of subjects with cardiac arrest or death within 24 h post infusion
GroupValue95% CI
UC-MSCs Group0
Control Group0
Number of Subjects With Serious Adverse Events by 31 Days After First Infusion Primary · 31 days

The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).

GroupValue95% CI
UC-MSCs Group2
Control Group8
Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90 Primary · 90 days

Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.

GroupValue95% CI
UC-MSCs Group41.67
Control Group66.67
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · 90 days

Total number of adverse events and serious adverse events as assessed by treating physician

Number of Adverse Events (not including SAEs)
GroupValue95% CI
UC-MSCs Group40
Control Group37
Number of Serious Adverse Events
GroupValue95% CI
UC-MSCs Group6
Control Group16
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity Primary · 90 days

Total number of adverse events plus serious adverse events categorized by severity.

Mild
GroupValue95% CI
UC-MSCs Group15
Control Group13
Moderate
GroupValue95% CI
UC-MSCs Group22
Control Group21
Severe
GroupValue95% CI
UC-MSCs Group9
Control Group19
Subjects With Adverse Events and Serious Adverse Events by Severity Primary · 90 days

Total number of subjects with adverse events and serious adverse events categorized by severity.

Mild
GroupValue95% CI
UC-MSCs Group7
Control Group5
Moderate
GroupValue95% CI
UC-MSCs Group7
Control Group8
Severe
GroupValue95% CI
UC-MSCs Group5
Control Group7
Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment Primary · 90 days

Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.

Unrelated
GroupValue95% CI
UC-MSCs Group42
Control Group45
Unlikely
GroupValue95% CI
UC-MSCs Group3
Control Group7
Possible
GroupValue95% CI
UC-MSCs Group1
Control Group1
Probably
GroupValue95% CI
UC-MSCs Group0
Control Group0
Definite
GroupValue95% CI
UC-MSCs Group0
Control Group0
Subjects With Adverse Events by Relatedness to Treatment Primary · 90 days

Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional

Unrelated
GroupValue95% CI
UC-MSCs Group8
Control Group10
Unlikely
GroupValue95% CI
UC-MSCs Group1
Control Group4
Possible
GroupValue95% CI
UC-MSCs Group1
Control Group1
Probable
GroupValue95% CI
UC-MSCs Group0
Control Group0
Defininte
GroupValue95% CI
UC-MSCs Group0
Control Group0
Survival at 31 Days Post First Infusion Secondary · 31 Days

Number of participants that are alive at 31 days post first infusion follow up corresponding to 28 day post second infusion.

GroupValue95% CI
UC-MSCs Group10
Control Group5
Survival at 60 Days Post First Infusion Secondary · 60 days

Number of participants alive at 60 days post first infusion follow up.

GroupValue95% CI
UC-MSCs Group9
Control Group5
Time to Recovery Secondary · 31 days

Time to discharge or, if the subject was hospitalized, no longer requiring supplemental oxygen and no longer requiring COVID-19-related medical care by 31 days. The numbers represent days at which 25%, 50%, 75% subjects within the treatment group had recovered.

Days by which 75% of subjects were recovered
GroupValue95% CI
UC-MSCs Group2313.00 – NA
Control GroupNANA – NA
Days by which 50% of subjects were recovered
GroupValue95% CI
UC-MSCs Group156 – 23
Control GroupNA10 – NA
Days by which 25% of subjects were recovered
GroupValue95% CI
UC-MSCs Group83 – 15
Control Group129 – NA
Ventilator-Free Days Throughout 28 Days Post Second Infusion Secondary · 28 days post second infusion

Number of days participants were off ventilators during 28 days post second infusion.

GroupValue95% CI
UC-MSCs Group2824 – 28
Control Group00 – 28

Adverse events — posted to ClinicalTrials.gov

Time frame: 3 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

UC-MSCs Group
Serious: 5/12 (42%)
Deaths: 3/12
Control Group
Serious: 8/12 (67%)
Deaths: 7/12

Serious adverse events (15 terms)

ReactionSystemUC-MSCs GroupControl Group
[DEATH] Cardiac Arrest-Death/Cardiopulmonary Arrest-Death/Asystole -DeathCardiac disorders——
Cardiac Arrest/Pulseless Electrical Activity Cardiac Arrest/Cardiac Arrest Secondary to Acute RespirCardiac disorders——
[DEATH] Multisystem Organ Failure (Death)/Multiple Organ Dysfunction Syndrome-DeathGeneral disorders——
GI Bleeding 2ry to Clostridium Difficile InfectionGastrointestinal disorders——
Colon PerforationGastrointestinal disorders——
Cardiact Arrest-Death due to Difficult IntubationCardiac disorders——
Acute respiratory Failure 2ry to COVID-DeathRespiratory, thoracic and mediastinal disorders——
Atrial FlutterCardiac disorders——
Death-Acute Hypoxemic Respiratory Failure Secondary to COVID-19 PneumonitisRespiratory, thoracic and mediastinal disorders——
PsychosisPsychiatric disorders——
Traumatic Tension Pneumotorax post-CPRRespiratory, thoracic and mediastinal disorders——
Severe Respiratory AcidosisRespiratory, thoracic and mediastinal disorders——
HyperkalemiaMetabolism and nutrition disorders——
Severe Metabolic AcidosisMetabolism and nutrition disorders——
Septic Shock-Hospital acquired Pseudomona Aeruginosa bacteremiaInfections and infestations——
Other adverse events (46 terms — click to expand)

ReactionSystemUC-MSCs GroupControl Group
Acute Kidney Injury/Oliguric Acute Kidney Injury/ Anuric Acute Kidney Injury/Acute Kidney Injury (AKRenal and urinary disorders——
Worsening of Hypoxemia/Deterioration of HypoxiaRespiratory, thoracic and mediastinal disorders——
Leukocytosis/Leukocytosis (Increased WBC)Blood and lymphatic system disorders——
FeverGeneral disorders——
TachycardiaCardiac disorders——
HyperglycemiaEndocrine disorders——
Transaminitis/Transaminitis-Liver ShockHepatobiliary disorders——
AnemiaBlood and lymphatic system disorders——
Thrombocytopenia/Heparin-induced ThrombocytopeniaBlood and lymphatic system disorders——
HypernatremiaMetabolism and nutrition disorders——
MRSA Hospital Acquired PneumoniaRespiratory, thoracic and mediastinal disorders——
Atrial FibrillationCardiac disorders——
BradycardiaCardiac disorders——
Exacerbation of COVID ARDS-Septic ShockInfections and infestations——
Tachycardia after infusion of Investigational ProductCardiac disorders——
Clostridium Difficile InfectionGastrointestinal disorders——
Mild Gastrointestinal BleedingGastrointestinal disorders——
Increased ALT, AST, and Alkaline PhosphataseHepatobiliary disorders——
Increased Direct BilirubinHepatobiliary disorders——
Abnormal UrinalysisRenal and urinary disorders——
CandiduriaRenal and urinary disorders——
Severe ThrombocytopeniaBlood and lymphatic system disorders——
ThrombocytosisBlood and lymphatic system disorders——
Bilateral Common Femoral Vein DVTVascular disorders——
Candida Albicans FungemiaInfections and infestations——
Mild HyponatremiaMetabolism and nutrition disorders——
HypokalemiaMetabolism and nutrition disorders——
HyperkalemiaMetabolism and nutrition disorders——
MRSA BacteremiaInfections and infestations——
Paenebacillus Pabuli BacteremiaInfections and infestations——
Positive Blood Culture Streptococcus Mitis and Streptococcus OralisInfections and infestations——
Staphylococcus haemolyticus bacteremia and Candida orthopsilosi FungemiaInfections and infestations——
Staphylococcus Hominis Bacteremia/Staphylococcus BacteremiaInfections and infestations——
Left Calf CollectionMusculoskeletal and connective tissue disorders——
EncephalopathyNervous system disorders——
Dysconjugated gazeNervous system disorders——
Urinary Tract InfectionRenal and urinary disorders——
PneumoperitoneumRespiratory, thoracic and mediastinal disorders——
Aspiration Pneumonitis, suspectedRespiratory, thoracic and mediastinal disorders——
BradypneaRespiratory, thoracic and mediastinal disorders——

Most-reported serious reactions: [DEATH] Cardiac Arrest-Death/Cardiopulmonary Arrest-Death/Asystole -Death, Cardiac Arrest/Pulseless Electrical Activity Cardiac Arrest/Cardiac Arrest Secondary to Acute Respir, [DEATH] Multisystem Organ Failure (Death)/Multiple Organ Dysfunction Syndrome-Death, GI Bleeding 2ry to Clostridium Difficile Infection, Colon Perforation, Cardiact Arrest-Death due to Difficult Intubation, Acute respiratory Failure 2ry to COVID-Death, Atrial Flutter.

Data from ClinicalTrials.gov NCT04355728 adverse events section.

Sponsor's own description

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Challenges and advances in clinical applications of mesenchymal stromal cells.
    Zhou T, Yuan Z, Weng J, Pei D, et al · · 2021 · cited 489× · PMID 33579329 · DOI 10.1186/s13045-021-01037-x
  2. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.
    Lanzoni G, Linetsky E, Correa D, Messinger Cayetano S, et al · · 2021 · cited 313× · PMID 33400390 · DOI 10.1002/sctm.20-0472
  3. A Brief Overview of Global Trends in MSC-Based Cell Therapy.
    Jovic D, Yu Y, Wang D, Wang K, et al · · 2022 · cited 186× · PMID 35344199 · DOI 10.1007/s12015-022-10369-1
  4. Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?
    Galderisi U, Peluso G, Di Bernardo G. · · 2022 · cited 175× · PMID 34398443 · DOI 10.1007/s12015-021-10231-w
  5. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.
    Markov A, Thangavelu L, Aravindhan S, Zekiy AO, et al · · 2021 · cited 174× · PMID 33736695 · DOI 10.1186/s13287-021-02265-1
  6. Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.
    Huang Y, Wu Q, Tam PKH. · · 2022 · cited 143× · PMID 36077421 · DOI 10.3390/ijms231710023
  7. Mesenchymal stem cell therapy for severe COVID-19.
    Shi L, Wang L, Xu R, Zhang C, et al · · 2021 · cited 76× · PMID 34497264 · DOI 10.1038/s41392-021-00754-6
  8. Extracellular vesicles: new players in regulating vascular barrier function.
    Chatterjee V, Yang X, Ma Y, Wu MH, et al · · 2020 · cited 56× · PMID 33035434 · DOI 10.1152/ajpheart.00579.2020

Verify or expand the search:

Other recruiting trials for Corona Virus Infection

Currently open trials in the same condition.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04355728.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing