Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Annals of Intensive Care

Table 1 Pre-specified infusion associated adverse events for START

Within six hours of the MSCs infusion	Within 24 hours of the MSCs infusion^b
1. An increase in vasopressor dose greater than or equal to a predefined threshold:	1. Cardiac arrest
> 10 mcg/minute norepinephrine	2. Death
> 100 mcg/minute phenylephrine
> 10 mcg/kg/minute dopamine
> 0.1 mcg/kg/minute of epinephrine^a
Addition of a third vasopressor
2. New ventricular tachycardia, ventricular fibrillation or asystole
3. New cardiac arrhythmia requiring cardioversion
4. Hypoxemia requiring an increase in the fraction of inspired oxygen of 0.2 or more and an increase in the level of PEEP of 5 cmH₂0 or more to maintain transcutaneous oxygen saturations in the target range of 88 to 95%
5. A clinical scenario consistent with transfusion incompatibility or transfusion-related infection (urticaria, wheezing)

^aAlthough patients on epinephrine were excluded from the original clinical trial protocol, because of the current Surviving Sepsis Guidelines and the use of epinephrine as a first line vasopressor in at least one study hospital ICU, the protocol was amended to allow patients on a modest dose of epinephrine to be included in the trial and to define a pre-specified infusion associated event based on epinephrine dosing.
^bSince patients who are moribund and not expected to survive 24 hours are excluded from the study.