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

Not Applicable

• Conditions: Acute Respiratory Distress Syndrome
• Interventions: Biological: umbilical cord derived mesenchymal stem cells (UCMSCs) suspension; Biological: normal saline

• Registration Number: NCT03608592
• Lead Sponsor: 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.

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

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2018-07-10
• Study First Submitted QC: 2018-07-23
• Study First Posted: 2018-08-01
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-31
• Last Update Posted: 2019-09-04
• Primary Completion: 2020-08-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
UCMSCs group	normal saline	Intravenous infusion of 1million UCMSCs per kilogram body weight suspended in 100ml normal saline, infusion duration 30-60min.
UCMSCs group	umbilical cord derived mesenchymal stem cells (UCMSCs) suspension	Intravenous infusion of 1million UCMSCs per kilogram body weight suspended in 100ml normal saline, infusion duration 30-60min.

Primary Outcome Measures

Name	Time	Method
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 .
Mortality	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

Name	Time	Method
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
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
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.
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
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.
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.

Trial Locations

Locations (1)

Huimin Yi; 🇨🇳 Guangzhou, Guangdong, China