Methods: A computer program was created to generate stopping rules based on specified error rates, trial size, and RR and median TTP of interest and disinterest for a two-stage phase II trial. Rules were generated for stage II such that the null hypothesis (H(nul)) was rejected if either RR or TTP met desired thresholds, and accepted if both did not. Assuming an exponential distribution for progression, EPD thresholds

were determined based on specified TTP values. Stopping rules were generated for stage I such that H(nul) was accepted and the study stopped if both RR and EPD were unacceptable.

Results: Patient thresholds were generated for RR, median TTP, and EPD which achieved specified error rates and which allowed early stopping based on RR and EPD. For smaller proportional differences between interesting and disinteresting values CA4P mouse HTS assay of RR or TTP, larger trials

are required to maintain alpha error, and early stopping is more common with a larger first stage.

Conclusion: Stopping rules are provided for phase II trials for drugs which have either a desirable RR or TTP. In addition, early stopping can be achieved using RR and EPD.”
“Background: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. Acute coronary obstruction is a major cause of OHCA. We hypothesize that early coronary reperfusion will improve 24 h-survival Ganetespib order and neurological outcomes.

Methods: Total occlusion of the mid LAD was induced by balloon inflation in 27 pigs. After 5 min, VF was induced and left untreated for 8 min. If return of spontaneous circulation (ROSC) was achieved within 15 min (21/27 animals) of cardiopulmonary resuscitation

(CPR), animals were randomized to a total of either 45 min (group A) or 4 h (group B) of LAD occlusion. Animals without ROSC after 15 min of CPR were classified as refractory VF (group C). In those pigs, CPR was continued up to 45 min of total LAD occlusion at which point reperfusion was achieved. CPR was continued until ROSC or another 10 min of CPR had been performed. Primary endpoints for groups A and B were 24-h survival and cerebral performance category (CPC). Primary endpoint for group C was ROSC before or after reperfusion.

Results: Early compared to late reperfusion improved survival (10/11 versus 4/10, p = 0.02), mean CPC (1.4 +/- 0.7 versus 2.5 +/- 0.6, p = 0.017), LVEF (43 +/- 13 versus 32 +/- 9%, p = 0.01), troponin I (37 +/- 28 versus 99 +/- 12, p = 0.005) and CK-MB (11 +/- 4 versus 20.1 +/- 5, p = 0.031) at 24-h after ROSC. ROSC was achieved in 4/6 animals only after reperfusion in group C.

Conclusions: Early reperfusion after ischemic cardiac arrest improved 24 h survival rate and neurological function.