Back to resultsHuman Umbilical Cord Mesenchymal Stem Cells (MSCs) Therapy in ARDS (ARDS)
Primary Purpose
Acute Respiratory Distress Syndrome
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
umbilical cord derived mesenchymal stem cells (UCMSCs) suspension
normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring refractory acuter respiratory distress syndrome, mesenchymal stem cells, salvage therapy
Eligibility Criteria
Inclusion Criteria:
- Aged≥18 years old;
- 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:
- Any malignant disease;
- Cardiogenic pulmonary edema;
- Over 50% atelectasis either lung lobe in X-ray;
- Pregnancy or perinatal or lactation;
- Previous end stage respiratory disease;
- More than 3 organs failure;
- Liver failure with MELD(Model For End-Stage Liver Disease) score>40;
- Stage III or IV pulmonary hypertension;
- None invasive arterial and central venous catheter;
- Concurrent deep venous thrombus or pulmonary embolism in 3 months;
- Cerebral hernia;
- More than 96 hours after ARDS onset.
Sites / Locations
- Huimin YiRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
UCMSCs group
Arm Description
Intravenous infusion of 1million UCMSCs per kilogram body weight suspended in 100ml normal saline, infusion duration 30-60min.
Outcomes
Primary Outcome Measures
Infusion associated events
Incidence of prescribed adverse events or unprescribed events agreed by investigators and consultant .
Mortality
All cause mortality. Cause of death, exact survival status (death/survival) and time (days) will also be recorded
Secondary Outcome Measures
Ventilation free days(VFDs)
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:
The patient dies in 28 days;
Ventilator never be weaned;
Censored case with ventilator never being weaned.
Oxygenation index(OI) changes
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.
Lung injury score(LIS)
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.
Positive end expiratory pressure(PEEP)
Monitored by ventilator and recorded per hour, obtain the average value of the day. unit-cmH20
Plateau pressure(Pplat)
Monitored by ventilator in one inspiration pause, measured 4 times a day. Record the average value of the day. unit-cmH20
Driving pressure
Calculate the driving pressure by Pplat minus PEEP, measured 4 times a day. Record the average value of the day. unit-cmH20
Static compliance
Calculate the static compliance by the following formula:
static compliance=tidal volume/(Pplat-PEEP), unit-ml/cmH2O
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03608592
Brief Title
Human Umbilical Cord Mesenchymal Stem Cells (MSCs) Therapy in ARDS
Acronym
ARDS
Official Title
Human Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Acute Respiratory Distress Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
August 1, 2020 (Anticipated)
Study Completion Date
December 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
refractory acuter respiratory distress syndrome, mesenchymal stem cells, salvage therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
UCMSCs group
Arm Type
Experimental
Arm Description
Intravenous infusion of 1million UCMSCs per kilogram body weight suspended in 100ml normal saline, infusion duration 30-60min.
Intervention Type
Biological
Intervention Name(s)
umbilical cord derived mesenchymal stem cells (UCMSCs) suspension
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
normal saline
Intervention Description
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 Measure Information:
Title
Infusion associated events
Description
Incidence of prescribed adverse events or unprescribed events agreed by investigators and consultant .
Time Frame
From infusion beginning to the second day, 24 hours
Title
Mortality
Description
All cause mortality. Cause of death, exact survival status (death/survival) and time (days) will also be recorded
Time Frame
In 60 days after enrolled
Secondary Outcome Measure Information:
Title
Ventilation free days(VFDs)
Description
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:
The patient dies in 28 days;
Ventilator never be weaned;
Censored case with ventilator never being weaned.
Time Frame
From the day of UCMSCs use(day 0) to day 28
Title
Oxygenation index(OI) changes
Description
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.
Time Frame
From day 0 to day 7, each day
Title
Lung injury score(LIS)
Description
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.
Time Frame
From day 0 to day 7, day0,1,3,7
Title
Positive end expiratory pressure(PEEP)
Description
Monitored by ventilator and recorded per hour, obtain the average value of the day. unit-cmH20
Time Frame
From day 0 to day 7, each day
Title
Plateau pressure(Pplat)
Description
Monitored by ventilator in one inspiration pause, measured 4 times a day. Record the average value of the day. unit-cmH20
Time Frame
From day 0 to day 7, each day
Title
Driving pressure
Description
Calculate the driving pressure by Pplat minus PEEP, measured 4 times a day. Record the average value of the day. unit-cmH20
Time Frame
From day 0 to day 7, each day
Title
Static compliance
Description
Calculate the static compliance by the following formula:
static compliance=tidal volume/(Pplat-PEEP), unit-ml/cmH2O
Time Frame
From day 0 to day 7, each day
Other Pre-specified Outcome Measures:
Title
Epithelial injury biomarker-KL6
Description
Detect Krebs von den Lungen-6(KL6) level in bronchoalveolar fluid (BALF), unit-U/ml
Time Frame
From day 0 to day 7, day0, 1,3,7
Title
Endothelial injury biomarker-Ang2
Description
Detect the angiopoietin (Ang2) level in plasma, unit-pg/ml
Time Frame
From day 0 to day 7, day0, 1,3,7
Title
Tumor necrosis factor a(TNFa)
Description
Detect the TNFa in plasma and in BALF, unit-pg/ml
Time Frame
From day 0 to day 7, day0, 1,3,7
Title
Interleukin 8(IL8)
Description
Detect the IL8 in plasma and in BALF, unit-pg/ml
Time Frame
From day 0 to day 7, day0, 1,3,7
Title
Interleukin 6(IL6)
Description
Detect the IL6 in plasma and in BALF, unit-pg/ml
Time Frame
From day 0 to day 7, day0, 1,3,7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged≥18 years old;
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:
Any malignant disease;
Cardiogenic pulmonary edema;
Over 50% atelectasis either lung lobe in X-ray;
Pregnancy or perinatal or lactation;
Previous end stage respiratory disease;
More than 3 organs failure;
Liver failure with MELD(Model For End-Stage Liver Disease) score>40;
Stage III or IV pulmonary hypertension;
None invasive arterial and central venous catheter;
Concurrent deep venous thrombus or pulmonary embolism in 3 months;
Cerebral hernia;
More than 96 hours after ARDS onset.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huimin Yi, Doctor
Phone
86-020-85252673
Email
ylhmin@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huimin Yi
Organizational Affiliation
The 3rd affiliated hospital of Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huimin Yi
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haijin Lv
Phone
2082179173
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Human Umbilical Cord Mesenchymal Stem Cells (MSCs) Therapy in ARDS
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