Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome (START)

We carried out a randomized, double-blind placebo-controlled trial on allogeneic bone marrow
derived mesenchymal stromal cells for treatment of moderate to severe ARDS in 60 patients, 40
MSC and 20 placebo, in a 2:1 randomization. The primary endpoint was safety. The results
showed no safety issues. Secondary endpoints for clinical and biological variables were
studied as well. Plasma Ang-2 significantly decline in the MSC treated group compared to the
Placebo patients. There were no other significant differences in the other secondary
endpoints.

Inclusion Criteria:

Patients will be eligible for inclusion if they meet all of the below criteria. Criteria
1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a
PaO2/FiO2 ratio < 200 with at least 8 cm H2O positive end-expiratory airway pressure
(PEEP)

2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph

3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

Exclusion Criteria:

1. Age less than 18 years

2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of
ARDS

3. Pregnant or breast-feeding

4. Prisoner

5. Presence of any active malignancy (other than non-melanoma skin cancer) that required
treatment within the last 2 years

6. Any other irreversible disease or condition for which 6-month mortality is estimated
to be greater than 50%

7. Moderate to severe liver failure (Childs-Pugh Score > 12)

8. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen

9. Patient, surrogate, or physician not committed to full support (exception: a patient
will not be excluded if he/she would receive all supportive care except for attempts
at resuscitation from cardiac arrest)

10. Major trauma in the prior 5 days

11. Lung transplant patient

12. No consent/inability to obtain consent

13. Moribund patient not expected to survive 24 hours

14. WHO Class III or IV pulmonary hypertension

15. Documented deep venous thrombosis or pulmonary embolism within past 3 months

16. No arterial line/no intent to place an arterial line

17. No intent/unwillingness to follow lung protective ventilation strategy or fluid
management protocol

18. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory
ventilation (HFOV)