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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mesenchymal Stem Cell Infusion | Experimental | Mesenchymal stem cells cultured and extracted from bone marrow of enrolled patients are infused. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesenchymal Stem Cell | Biological | Mesenchymal stem cells will be intravenously infused. Mesenchymal stem cells will be cultured and extracted from the bone marrow of the patients. |
| 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 |
| 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 |
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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.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sang Bum Hong, MD | Contact | +82-10-6824-9767 | hongsangbum@gmail.com | |
| Dong Hyun Lee, MD | Contact | +82-10-6476-0706 | rvotvt@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Sang Bum Hong, M.D. | Asan Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Recruiting | Seoul | 138-736 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17356114 | Background | Calfee CS, Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest. 2007 Mar;131(3):913-920. doi: 10.1378/chest.06-1743. | |
| 16236739 | Background | Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. doi: 10.1056/NEJMoa050333. |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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|
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 |
| 20384521 | Background | D'Agostino B, Sullo N, Siniscalco D, De Angelis A, Rossi F. Mesenchymal stem cell therapy for the treatment of chronic obstructive pulmonary disease. Expert Opin Biol Ther. 2010 May;10(5):681-7. doi: 10.1517/14712591003610614. |
| 19691441 | Background | Lee JW, Gupta N, Serikov V, Matthay MA. Potential application of mesenchymal stem cells in acute lung injury. Expert Opin Biol Ther. 2009 Oct;9(10):1259-70. doi: 10.1517/14712590903213651. |
| 17212702 | Background | Stagg J. Immune regulation by mesenchymal stem cells: two sides to the coin. Tissue Antigens. 2007 Jan;69(1):1-9. doi: 10.1111/j.1399-0039.2006.00739.x. |
| 17641052 | Background | Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. doi: 10.4049/jimmunol.179.3.1855. |
| 19721001 | Background | Lee JW, Fang X, Gupta N, Serikov V, Matthay MA. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16357-62. doi: 10.1073/pnas.0907996106. Epub 2009 Aug 31. |
| 17569781 | Background | Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11002-7. doi: 10.1073/pnas.0704421104. Epub 2007 Jun 14. |
| 19497992 | Background | Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009 Jul;175(1):303-13. doi: 10.2353/ajpath.2009.080629. Epub 2009 Jun 4. |
| 15891110 | Background | Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005 Aug;33(2):145-52. doi: 10.1165/rcmb.2004-0330OC. Epub 2005 May 12. |
| 18508443 | Background | Zhen G, Liu H, Gu N, Zhang H, Xu Y, Zhang Z. Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Front Biosci. 2008 May 1;13:3415-22. doi: 10.2741/2936. |