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

We carried out a randomized, double-blind placebo-controlled trial of allogeneic bone marrow derived human mesenchymal stromal cells for treatment of moderate to severe ARDS in 60 patients, 40 MSC and 20 placebo, in a 2:1 randomization. This trial is the extension of the Phase 1 pilot trial (NCT01775774). Patients were followed daily for adverse events through day 28, death or hospital discharge, whichever occurs first. Vital status was collected at 6 and 12 months after study enrollment.

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:

• 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)
• Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
• No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

Exclusion criteria

• Age less than 18 years
• Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
• Pregnant or breast-feeding
• Prisoner
• Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
• Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
• Moderate to severe liver failure (Childs-Pugh Score > 12)
• Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
• 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)
• Major trauma in the prior 5 days
• Lung transplant patient
• No consent/inability to obtain consent
• Moribund patient not expected to survive 24 hours
• World Health Organization (WHO) Class III or IV pulmonary hypertension
• Documented deep venous thrombosis or pulmonary embolism within past 3 months
• No arterial line/no intent to place an arterial line
• No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
• Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)