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

Human Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Acute Respiratory Distress Syndrome

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.

Study Overview

• Status: Unknown
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Biological: umbilical cord derived mesenchymal stem cells (UCMSCs) suspension; Biological: normal saline

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 Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Huimin Yi
      • Contact: Haijin Lv; Phone Number: 2082179173

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infusion associated events	Incidence of prescribed adverse events or unprescribed events agreed by investigators and consultant .	From infusion beginning to the second day, 24 hours
Mortality	All cause mortality. Cause of death, exact survival status (death/survival) and time (days) will also be recorded	In 60 days after enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the day of UCMSCs use(day 0) to day 28
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.	From day 0 to day 7, each day
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.	From day 0 to day 7, day0,1,3,7
Positive end expiratory pressure(PEEP)	Monitored by ventilator and recorded per hour, obtain the average value of the day. unit-cmH20	From day 0 to day 7, each day
Plateau pressure(Pplat)	Monitored by ventilator in one inspiration pause, measured 4 times a day. Record the average value of the day. unit-cmH20	From day 0 to day 7, each day
Driving pressure	Calculate the driving pressure by Pplat minus PEEP, measured 4 times a day. Record the average value of the day. unit-cmH20	From day 0 to day 7, each day
Static compliance	Calculate the static compliance by the following formula: static compliance=tidal volume/(Pplat-PEEP), unit-ml/cmH2O	From day 0 to day 7, each day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epithelial injury biomarker-KL6	Detect Krebs von den Lungen-6(KL6) level in bronchoalveolar fluid (BALF), unit-U/ml	From day 0 to day 7, day0, 1,3,7
Endothelial injury biomarker-Ang2	Detect the angiopoietin (Ang2) level in plasma, unit-pg/ml	From day 0 to day 7, day0, 1,3,7
Tumor necrosis factor a(TNFa)	Detect the TNFa in plasma and in BALF, unit-pg/ml	From day 0 to day 7, day0, 1,3,7
Interleukin 8(IL8)	Detect the IL8 in plasma and in BALF, unit-pg/ml	From day 0 to day 7, day0, 1,3,7
Interleukin 6(IL6)	Detect the IL6 in plasma and in BALF, unit-pg/ml	From day 0 to day 7, day0, 1,3,7

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Huimin Yi, The 3rd affiliated hospital of Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ANTICIPATED): August 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 31, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: mesenchymal stem cells; salvage therapy; refractory acuter respiratory distress syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: QHJH201804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No