Acute Respiratory Distress Syndrome
Conditions
Keywords
refractory acuter respiratory distress syndrome, mesenchymal stem cells, salvage therapy
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
Interventions
BIOLOGICALumbilical 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.
BIOLOGICALnormal 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.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A package of 100ml normal saline with 10\^6/kg umbilical cord derived MSCs suspension will infused from central venous catheter.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | In 60 days after enrolled | All cause mortality. Cause of death, exact survival status (death/survival) and time (days) will also be recorded |
| Infusion associated events | From infusion beginning to the second day, 24 hours | Incidence of prescribed adverse events or unprescribed events agreed by investigators and consultant . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lung injury score(LIS) | 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. |
| Oxygenation index(OI) changes | 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. |
| Positive end expiratory pressure(PEEP) | From day 0 to day 7, each day | Monitored by ventilator and recorded per hour, obtain the average value of the day. unit-cmH20 |
| Plateau pressure(Pplat) | 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 |
| Driving pressure | 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 |
| Static compliance | 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 |
| Ventilation free days(VFDs) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Interleukin 8(IL8) | From day 0 to day 7, day0, 1,3,7 | Detect the IL8 in plasma and in BALF, unit-pg/ml |
| Interleukin 6(IL6) | From day 0 to day 7, day0, 1,3,7 | Detect the IL6 in plasma and in BALF, unit-pg/ml |
| Tumor necrosis factor a(TNFa) | From day 0 to day 7, day0, 1,3,7 | Detect the TNFa in plasma and in BALF, unit-pg/ml |
| Endothelial injury biomarker-Ang2 | From day 0 to day 7, day0, 1,3,7 | Detect the angiopoietin (Ang2) level in plasma, unit-pg/ml |
| Epithelial injury biomarker-KL6 | 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 |
Countries
China
Contacts
Primary ContactHuimin Yi, Doctor
Outcome results
None listed