Clinical trial NCT03608592: Human Umbilical Cord Mesenchymal Stem Cells (MSCs) Therapy in ARDS
Official title: Human Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Keywords: refractory acuter respiratory distress syndrome
mesenchymal stem cells
salvage therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2018-08-01
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A package of 100ml normal saline with 10\^6/kg umbilical cord derived MSCs suspension will infused from central venous catheter.
Primary purpose: TREATMENT

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

Eligibility 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.

Primary outcomes:
measure: Infusion associated events
timeFrame: From infusion beginning to the second day, 24 hours
measure: Mortality
timeFrame: In 60 days after enrolled
Secondary outcomes:
measure: Ventilation free days(VFDs)
timeFrame: From the day of UCMSCs use(day 0) to day 28
measure: Oxygenation index(OI) changes
timeFrame: From day 0 to day 7, each day
measure: Lung injury score(LIS)
timeFrame: From day 0 to day 7, day0,1,3,7
measure: Positive end expiratory pressure(PEEP)
timeFrame: From day 0 to day 7, each day
measure: Plateau pressure(Pplat)
timeFrame: From day 0 to day 7, each day
measure: Driving pressure
timeFrame: From day 0 to day 7, each day
measure: Static compliance
timeFrame: From day 0 to day 7, each day
Other outcomes:
measure: Epithelial injury biomarker-KL6
timeFrame: From day 0 to day 7, day0, 1,3,7
measure: Endothelial injury biomarker-Ang2
timeFrame: From day 0 to day 7, day0, 1,3,7
measure: Tumor necrosis factor a(TNFa)
timeFrame: From day 0 to day 7, day0, 1,3,7
measure: Interleukin 8(IL8)
timeFrame: From day 0 to day 7, day0, 1,3,7
measure: Interleukin 6(IL6)
timeFrame: From day 0 to day 7, day0, 1,3,7
Locations:
city: Guangzhou
country: China
facility: Huimin Yi
state: Guangdong
Study officials:
affiliation: The 3rd affiliated hospital of Sun Yat-sen University
name: Huimin Yi
role: PRINCIPAL_INVESTIGATOR
References: