Mesenchymal Stem Cell in Patients With Acute Severe Respiratory Failure

Study Overview
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Brief Summary
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Although the advent of advanced medical support for respiratory failure, the mortality rate of acute severe respiratory failure is still high and the life quality is frequently compromised from pulmonary fibrosis. The investigators hypothesize that the treatment using mesenchymal stem cell can be beneficial in patients with respiratory failure. The present study is a pilot study evaluating the efficacy and safety of mesenchymal stem cell treatment in patients with respiratory failure.

Detailed Description
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Although the advent of advanced medical support for respiratory failure, the mortality rate of acute severe respiratory failure is still reported to be more than 40%. The respiratory distress syndrome may develop in all ages resulting in progressive pulmonary fibrosis. A number of survivors from respiratory failure suffer from the sequelas of pulmonary fibrosis. However, the treatments of respiratory failure are limited to the correction of baseline disease, cardiopulmonary support, and conservative management to minimize the lung injury. There has not been any effective and specific treatment for respirator distress nor medicine to reduce mortality. There have been reports of mesenchymal stem cell experimental animals with chronic obstructive pulmonary disease, interstitial lung disease, and sepsis. In addition, the mesenchymal stem cell treatment showed beneficial effect in bleomycin endotoxin induced lung injury. Authors hypothesize that the mesenchymal stem cell treatment in patients with respiratory failure will show efficacy. We would conduct the present pilot study to evaluate the efficacy and safety in patients with respiratory failure and intend to suggest an additional alternative treatment option for those without additional treatment option.

Official Title
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A Pilot Study for the Efficacy and Safety of Mesenchymal Stem Cell in Acute Severe Respiratory Failure.

Conditions
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Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Biological: Mesenchymal Stem Cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ventilator care from respiratory failure Ventilator care for 7 or more days at least one of the followings PaO2/FiO2 = 200 or less when PEEP 5 cmH2O or more. PaCO2 = 50 mmHg or more when plateau pressure of 30 cmH2O or more. pH = 7.25 or less when plateau pressure of 30 cmH2O or more. No other treatment option except for lung transplantation and not candidate for recipient (organ failure, comorbid infection, economy,...) Ventilatory care with weaning failure 3 times or more Ventilator care requiring 7 days or more from the first self respiration to weaning of ventilator. PEEP, positive endexpiratory pressure Exclusion Criteria: Severe aplastic anemia Malignant hematologic disorder or history of stem cell treatment. Currently uncontrolled malignancy or history of solid cancer within 2 years HIV Infection Expected life < 3 months from other cause than the respiratory failure Pregnancy or breast feeding Expected hypersensitivity for study drug

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stem Cell Infusion<br>Mesenchymal stem cells cultured and extracted from bone marrow of enrolled patients are infused. | Biological: Mesenchymal Stem Cell<br>* Mesenchymal stem cells will be intravenously infused. Mesenchymal stem cells will be cultured and extracted from the bone marrow of the patients.<br>* Other names: Lungcellgram;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen index at 3 days after mesenchymal stem cell infusion | Oxygen index at 3 days after mesenchymal stem cell infusion. Oxygen index is calculated as follows; ((FiO2) x (Mean airway pressure)) / (PaO2) | 3 days after mesenchymal stem cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung mechanics | Lung mechanics includes arterial oxygen saturation, tidal volume, minute ventilation, and ratio of PaO2/FiO2. | at 3, 14, and 28 days after mesenchymal stem cell infusion | 
| Hemodynamic parameters | Systolic, diastolic, and mean arterial blood pressure Amount of required vasopressor Heart rate | at 3, 14, and 28 days after mesenchymal stem cell infusion | 
| Mortality | Death from any cause at 14 and 28 days after mesenchymal stem cell infusion | at 14 and 28 days after mesenchymal stem cell infusion | 
| Plasma cytokines | Interleukin (IL)-1, IL-6, IL-8, and IL-10 | at 3, 14, and 28 days after mesenchymal stem cell infusion | 
| Markers for inflammation and infection | Lactate, DIC score, SOFA score, C-reactive protein, and procalcitonin | at 3, 14, and 28 days after mesenchymal stem cell infusion | 
| Ventilator weaning parameters | Failure of ventilator weaning, weaning time, ventilation time | at 3, 14, and 28 days after mesenchymal stem cell infusion | 
| ICU and hospital stay | Total duration of ICU stay and hospital stay | at 28 days after mesenchymal stem cell infusion |