Inhomogeneity and temporal effects in AutoPulse Assisted Prehospital International Resuscitation--an exception from consent trial terminated early

Abstract

Background: The ASPIRE trial (AutoPulse Assisted Prehospital International Resuscitation) was multicenter exception from consent clinical trial that compared mechanical cardiopulmonary resuscitation (CPR) with a device (AutoPulse-CPR) to traditional manual CPR (manual-CPR) in out-of-hospital cardiac arrest. Enrollment was suspended early due to safety concerns. One site (site C) made a potentially important protocol change midtrial, and enrollment at that site was noted to be independently associated with outcome.

Methods: The study used a post hoc reanalysis of source data and documentation using standard statistical approaches evaluating for possible secular, temporal, and trial design, factors that may have related to the trial's outcome.

Results: The protocol change at site C also appears to have resulted in a delay in application of AutoPulse-CPR. Before and after the protocol change survival in patients receiving AutoPulse-CPR decreased from 19.6% to 4% (P = .024). Logistic regression analysis showed site C was significantly different (P = .008) from the remaining sites with respect to survival. Unlike site C, the other sites actually showed an increase over time in the primary end point of 4-hour survival (P = .008) favorable to AutoPulse-CPR. There did not appear to be significant safety (P = .42) nor efficacy concerns (P = .17) at these sites.

Conclusions: The difference in survival that caused early suspension of ASPIRE appears to have been limited to one site after its protocols change. At the time the trial was suspended, the outcomes of patients at the other sites appear to have been trending in favor of the intervention.

Trial registration: ClinicalTrials.gov NCT00120965.