Nobody likes a tie. People want clear winners and losers in their contests, with outcomes that are neat, clean and indisputable.
But sometimes a draw can be a pretty positive thing. For ZOLL Medical Corp., that was the case with the CIRC trial, which compared out-of-hospital cardiac arrest survival among patients treated with traditional CPR and CPR using ZOLL’s AutoPulse cardiac support pump, which automates compressions with a load-distributing band across the chest.
At November’s Resuscitation Science Symposium, investigators reported equivalent results between the groups. That had been known since January 2011, when the board monitoring the trial’s safety data shut down enrollment after concluding additional subjects couldn’t change an outcome that, based on more than 4,200 patients, was already statistically conclusive.
“I will confess, when the trial ended enrollment and the outcome was statistically equivalent, we’d hoped for something better,” says ZOLL President Jon Rennert. “But now I think of equivalence a little differently than I might have last January. What the trial really showed was that the AutoPulse was equivalent to probably the highest quality manual CPR ever recorded in a trial of this magnitude. We think that’s a big deal, because CPR isn’t performed very well in general.”
That’s not just corporate spin. The CIRC trial (for Circulation Improving Resuscitation Care; it was sponsored by ZOLL) had a unique design formulated to ensure the manual CPR against which the AutoPulse would be tested was of the highest caliber possible to obtain. To that end, trial designers incorporated some features:
• All providers were trained in a standardized deployment strategy crafted to minimize hands-off time, then monitored for compliance during the trial;
• A pretrial simulation study to ensure provider compliance with the trial protocol;
• Three distinct trial phases (training, run-in, statistical inclusion) to reduce biases like the Hawthorne effect;
• CPR monitoring using transthoracic impedance and accelerometer data;
• To reduce selection bias, subjects were randomized after the decision to resuscitate was made;
• Use of the Group Sequential Double Triangular test to determine superiority/inferiority/equivalence.
“We wanted to make sure we set the bar high for the control arm,” says Rennert. “We put a lot of measures in place to ensure the quality of the CPR was monitored religiously, and that feedback was provided after every case to each of the rescuing paramedics. It required an enormous investment of time and training and record-keeping and analysis to get the manual CPR quality as high as it was.”
It was worth it, though: Overall, the all-comers survival rate it achieved might be the highest ever recorded in a trial of this magnitude. Full results will be published in 2012, but it appears CIRC emphatically reinforces the value of good CPR; both arms had CPR fractions of an impressive 80%-plus over the first 20 minutes. Says Rennert: “We think it’s pretty clear that’s what drove the higher survival.”
The CIRC trial began in 2007 with sites in the U.S., Austria and the Netherlands, and involved deployment of more than 500 AutoPulses and training of more than 5,000 medics to use them. Its design was fully described in the journal Resuscitation in 2010.1 The authors of that piece, led by Brooke Lerner, PhD, of the Medical College of Wisconsin, noted conflicting results among previous human prehospital AutoPulse studies, and their desire to address “methodological issues that may have influenced [those] results.”
One of those instances may have been the ASPIRE (AutoPulse Assisted Prehospital International Resuscitation) trial, which was stopped early in 2005 when no difference was found in survival to four hours, but survival to and cerebral performance at hospital discharge were worse among the AutoPulse group.2 A potential queering factor was recognized later: One trial site changed protocols midstream, resulting in a subsequent delay to first chest compressions among its AutoPulse group that its manual group didn’t have. Survival decreased precipitously at that site after that change. Other sites, later investigators found, were trending in favor of the AutoPulse.3
To avoid such a problem, the CIRC crews integrated the AutoPulse after beginning manual CPR in a sequence structured to reduce hands-off time. Providers utilized the “pit crew” model of resuscitation, where each provider performs specific assigned duties, to minimize interruptions.
So the AutoPulse is as good as the best human CPR. Why should a system pay good money for equivalence? Why not just work to ensure your human CPR is as good as it can be?
A couple of reasons, if you’re ZOLL. The big one is that humans don’t generally provide top-quality CPR in the mayhem of the field or a moving ambulance. They push too slow or not deep enough; they tire; they’re distracted and interrupted and thrown off balance. Mechanical compressions are relentlessly regular and uniform. And of course, automating CPR frees providers to do other things, including remaining seated and restrained if they’re transporting with CPR in progress.
There’s also the effort and expense of achieving and maintaining top-notch human CPR, which doesn’t exactly occur naturally in the wild.
“I think if you’re an EMS agency looking at this trial,” says Ward Hamilton, ZOLL’s senior vice president and VP of marketing, “and your own survival statistics aren’t as good as what was demonstrated here, you have to ask how you can get better—how you can achieve the improved survival that’s possible here. Well, the reality is there are two paths forward. You can either commit to a very expensive ongoing effort of training and certification and postcase data review and debriefing, literally reading EKG strips compression by compression on every cardiac arrest forever. Or you can invest in an AutoPulse program. I think a lot of systems are going to look at that and say the AutoPulse is actually probably more cost-effective over time.”
The CIRC trial’s respected principal investigator also saw the tie as a win for the machine: “EMS around the world will look at the CIRC result as positive for the AutoPulse,” said Lars Wik, MD, PhD, of the National Competence Center of Emergency Medicine at Oslo University Hospital in Norway. “They know how difficult it is to perform manual CPR on a regular basis. My gut feeling is that the CIRC results will increase AutoPulse interest.”
“It’s a hard idea to get your mind around, because equivalence here is not a bad thing,” Hamilton adds. “Clearly you’d like to think some new technology is going to be better than something else. But to show that it’s as good as the best, that’s a pretty good outcome for a manufacturer.”
1. Lerner EB, Persse D, Souders CM, et al. Design of the Circulation Improving Resuscitation Care (CIRC) trial: a new state-of-the-art design for out-of-hospital cardiac arrest research. Resuscitation 82(3): 294–9, Mar 2011.
2. Hallstrom A, Rea TD, Sayre MR, et al. Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial. JAMA 295(22): 2,620–8, Jun 14, 2006.
3. Paradis NA, Young G, Lemeshow S, et al. Inhomogeneity and temporal effects in AutoPulse Assisted Prehospital International Resuscitation—an exception from consent trial terminated early. Am J Emerg Med 28(4): 391–8, May 2010.