August 31, 2012 (Örebro, Sweden) — In an unexpected move, the data safety and monitoring board (DSMB) for the world's largest study of thrombus aspiration in MI, Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE), has recommended that researchers continue enrollment in the trial .
The investigators had anticipated they would be asked to stop the trial, lead researcher Dr Ole Fröbert (Örebro University Hospital, Örebro, Sweden), told heartwire . They had adjudicated an interim analysis of the study, because as they approached the 5000 participants originally planned, "we could see that mortality was somewhat lower than expected for the entire group," he explained. "We thought in light of the other trials--especially INFUSE-AMI, which came out neutral--that probably TASTE would be neutral as well, so we had expected that the DSMB would advise us to terminate it."
We don't know which direction it's tipping in. Thrombus aspiration either saves lives or is a killer, we don't know.
Fröbert stressed, however, that this decision doesn't necessarily mean the trial is positive. "We don't know which direction it's tipping in. Thrombus aspiration either saves lives or is a killer, we don't know." But he added that any current signal toward a positive or negative outcome will likely just be a trend right now. Had there been a large enough signal suggesting harm of thrombus aspiration or an overt indication of its benefit, the DSMB would have recommended stopping the trial.
This decision is of great interest to observers worldwide, says Fröbert, "as TASTE most likely will dictate future guidelines, especially in the light of skepticism about the TAPAS trial and the disappointing results of INFUSE-AMI." The most recent ACC and AHA guidelines upgraded thrombus aspiration to a class IIa recommendation--it is reasonable to perform the procedure--with a level of evidence B (ie, limited populations evaluated). But it is widely acknowledged that large outcomes trials are needed to establish whether this procedure should be firmly adopted or discarded, he says.
"There have been so many inquiries to TASTE. In the past couple of months we have been continuously contacted by regulatory authorities (including the FDA), editors of guidelines, two leading scientific journals (wishing to publish), and colleagues about the status of TASTE," he added.
"Impressive" TASTE Trial, Plus TOTAL Results, Will Inform Guidelines
TASTE is important because of mixed results in previous trials of thrombus aspiration in STEMI, many of which were not adequately powered for hard clinical end points such as mortality. The large-scale TAPAS study demonstrated a survival benefit with this approach, but death was a secondary end point. And in the most recent study, INFUSE-AMI, the use of aspiration thrombectomy failed to have any demonstrable effect on myocardial infarct size, nor did it improve myocardial reperfusion, ST-segment resolution, or clinical event rates at 30 days.
We have been continuously contacted by regulatory authorities (including the FDA), editors of guidelines, and two leading scientific journals (wishing to publish).
Thrombus aspiration is "not rocket science," says Fröbert, explaining that it is easy, quick to perform, and a relatively cheap adjunct to PCI. But the relatively low-tech nature of it and the limited possibilities of future patents and economic revenue of thrombus-aspiration devices have meant that interest from medical-device companies to perform large scale studies in this area is low.
TASTE is completely investigator-driven, he observed, adding, "It's impressive that we've managed to include this many patients without much funding." It is a multicenter, prospective, randomized controlled clinical trial based on the Swedish Coronary Angiography and Angioplasty Registry [SCAAR] and is unusual because it uses an online national registry as a platform for case records, randomization, and follow-up." The latter will ensure 100% follow-up, unless any of the participants emigrate, Fröbert explained.
The original TASTE protocol recommended 5000 patients with STEMI to be randomly assigned to either conventional PCI or to thrombus aspiration followed by PCI . The primary end point is time to all-cause death at 30 days.
"The DSMB has now suggested we continue enrollment, to 7300 patients. We are currently at about 5600, and we hope to have this final number by the beginning of 2013," Fröbert said.
As well as TASTE, another large North American trial is ongoing, called TOTAL, which is enrolling 4000 patients with STEMI randomized to PCI with or without manual aspiration thrombectomy. The primary end point of that is a composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class 4 heart failure at six months. Fröbert understands TOTAL is due to report in 2014.
The TASTE investigators report no conflicts of interest.
Heartwire from Medscape © 2012 Medscape, LLC
Cite this: Surprise as DSMB Says TASTE Study of Thrombus Aspiration Should Continue - Medscape - Aug 31, 2012.