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Human Umbilical Cord Mesenchymal Stem Cells (MSCs) Therapy in ARDS (ARDS)

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ClinicalTrials.gov Identifier: NCT03608592
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Lv Haijin, Sun Yat-sen University

Brief Summary:
Acute respiratory distress syndrome (ARDS) is a devastating inflammatory and destructive disease in critical ill patients. Preclinical studies have shown a promising perspective of mesenchymal stem cells (MSCs) therapies in ARDS. But the safety and efficacy of umbilical cord MSCs (UCMSCs) have not yet been convinced in clinical trails. This study will explore the safety and life-rescue potential of UCMSCs in refracotry ARDS.

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Biological: umbilical cord derived mesenchymal stem cells (UCMSCs) suspension Biological: normal saline Not Applicable

Detailed Description:

This is a single arm study. According Berlin definition (2012), moderate or severe adult ARDS patients who fail to improve oxygenation (PaO2/FiO2 increase over 20%) in the first 24h or 8h after diagnosis will be enrolled. A salvage package of 10^6/kg suspended UCMSCs in 100ml normal saline or only 100ml normal saline will be infused through central venous catheter. Infusion associated events (IAEs) in 24 hours will be closely monitored. Compared with propensity score matched controls, mortality in 28 days as the primary outcomes. oxygenation index, ventilator parameters, lung injury biomarkers and clinical outcomes as secondary outcomes will be analyzed.

This is a revised trail from its previous registered pilot RCT, approved by Ethic Committe of Stem Cells Trails (ECSCT) of 3rd affiliated hospital of Sun Yat-Sen university


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group Assignment
Intervention Model Description: A package of 100ml normal saline with 10^6/kg umbilical cord derived MSCs suspension will infused from central venous catheter.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Human Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Acute Respiratory Distress Syndrome
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
Experimental: UCMSCs group
Intravenous infusion of 1million UCMSCs per kilogram body weight suspended in 100ml normal saline, infusion duration 30-60min.
Biological: umbilical cord derived mesenchymal stem cells (UCMSCs) suspension
Clinical grade human umbilical cord derived mesenchymal stem cells (passage 3-5) suspension are provided by biotherapy center of the third affiliated hospital of Sun Yat Sen University. Cells are made of suspension packages (60million cells in 100ml normal saline per bag) and infused intravenously in 2 hours.

Biological: normal saline
A bag of 100ml clinical grade normal saline are also provided by biotherapy center of the third affiliated hospital of Sun Yat Sen University.




Primary Outcome Measures :
  1. Infusion associated events [ Time Frame: From infusion beginning to the second day, 24 hours ]
    Incidence of prescribed adverse events or unprescribed events agreed by investigators and consultant .

  2. Mortality [ Time Frame: In 60 days after enrolled ]
    All cause mortality. Cause of death, exact survival status (death/survival) and time (days) will also be recorded


Secondary Outcome Measures :
  1. Ventilation free days(VFDs) [ Time Frame: From the day of UCMSCs use(day 0) to day 28 ]

    The days without invasive ventilator support(at least 2 consecutive calendar days) in 28 days.

    If the ventilator weaned multiple times, VFDs is the sum of the days without ventilator support.

    If any of following occurring in 28 days, VFDs equals 0:

    1. The patient dies in 28 days;
    2. Ventilator never be weaned;
    3. Censored case with ventilator never being weaned.

  2. Oxygenation index(OI) changes [ Time Frame: From day 0 to day 7, each day ]
    The oxygenation index(OI)=partial pressure of oxygen in arterial blood(PaO2) divide inspiration fraction of oxygen(FiO2). OI is measured at day0, day1,day3,day7.

  3. Lung injury score(LIS) [ Time Frame: From day 0 to day 7, day0,1,3,7 ]

    Murray lung injury scores (LIS) consist of the following 4 parts:

    A.Hypoxemia (PaO2/FiO2≥300, 225-299,175-224,100-174,<100, assigned 0,1,2,3,4 scores respectively); B.PEEP (cmH2O) (≤5,6-8,9-11,11-14,≥15, assigned 0,1,2,3,4 scores respectively) ; C.Compliance (ml/cmH2O)(≥80,60-79,40-59,20-39,≤19, assigned 0,1,2,3,4 scores respectively); D.Quadrants infiltrated in Chest X-Ray(CXR) (0,1,2,3,4, assigned 0,1,2,3,4 scores respectively).

    The total LIS score is obtained by dividing the total sum of points by the number of criteria present. For example, if only 3 criteria are answered to, the total sum is divided by 3 to reveal the final score.

    The LIS score ranges between 0 and 4, with scores closer to 4 indicating severe acute lung injury.


  4. Positive end expiratory pressure(PEEP) [ Time Frame: From day 0 to day 7, each day ]
    Monitored by ventilator and recorded per hour, obtain the average value of the day. unit-cmH20

  5. Plateau pressure(Pplat) [ Time Frame: From day 0 to day 7, each day ]
    Monitored by ventilator in one inspiration pause, measured 4 times a day. Record the average value of the day. unit-cmH20

  6. Driving pressure [ Time Frame: From day 0 to day 7, each day ]
    Calculate the driving pressure by Pplat minus PEEP, measured 4 times a day. Record the average value of the day. unit-cmH20

  7. Static compliance [ Time Frame: From day 0 to day 7, each day ]

    Calculate the static compliance by the following formula:

    static compliance=tidal volume/(Pplat-PEEP), unit-ml/cmH2O



Other Outcome Measures:
  1. Epithelial injury biomarker-KL6 [ Time Frame: From day 0 to day 7, day0, 1,3,7 ]
    Detect Krebs von den Lungen-6(KL6) level in bronchoalveolar fluid (BALF), unit-U/ml

  2. Endothelial injury biomarker-Ang2 [ Time Frame: From day 0 to day 7, day0, 1,3,7 ]
    Detect the angiopoietin (Ang2) level in plasma, unit-pg/ml

  3. Tumor necrosis factor a(TNFa) [ Time Frame: From day 0 to day 7, day0, 1,3,7 ]
    Detect the TNFa in plasma and in BALF, unit-pg/ml

  4. Interleukin 8(IL8) [ Time Frame: From day 0 to day 7, day0, 1,3,7 ]
    Detect the IL8 in plasma and in BALF, unit-pg/ml

  5. Interleukin 6(IL6) [ Time Frame: From day 0 to day 7, day0, 1,3,7 ]
    Detect the IL6 in plasma and in BALF, unit-pg/ml



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged≥18 years old;
  2. Including all the criteria:

(1) Invasive ventilation, OI(PaO2/FiO2)<200; (2) PEEP≥8cmH2O; (3) Bilateral infiltration of lung in X-ray or CT; (4) In 1 week after onset; (5) Still OI<200 after protective ventilation or conservative fluid management.

Exclusion Criteria:

  1. Any malignant disease;
  2. Cardiogenic pulmonary edema;
  3. Over 50% atelectasis either lung lobe in X-ray;
  4. Pregnancy or perinatal or lactation;
  5. Previous end stage respiratory disease;
  6. More than 3 organs failure;
  7. Liver failure with MELD(Model For End-Stage Liver Disease) score>40;
  8. Stage III or IV pulmonary hypertension;
  9. None invasive arterial and central venous catheter;
  10. Concurrent deep venous thrombus or pulmonary embolism in 3 months;
  11. Cerebral hernia;
  12. More than 96 hours after ARDS onset.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03608592


Contacts
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Contact: Huimin Yi, Doctor 86-020-85252673 ylhmin@hotmail.com

Locations
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China, Guangdong
Huimin Yi Recruiting
Guangzhou, Guangdong, China, 510630
Contact: Haijin Lv    2082179173      
Sponsors and Collaborators
Sun Yat-sen University
Investigators
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Principal Investigator: Huimin Yi The 3rd affiliated hospital of Sun Yat-sen University

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Responsible Party: Lv Haijin, attending physician, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT03608592     History of Changes
Other Study ID Numbers: QHJH201804
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lv Haijin, Sun Yat-sen University:
refractory acuter respiratory distress syndrome
mesenchymal stem cells
salvage therapy
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Syndrome
Respiratory Tract Diseases
Infant, Newborn, Diseases
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiration Disorders
Infant, Premature, Diseases
Lung Injury