The International Subarachnoid Aneurysm Trial (ISAT) was a large multicenter, prospective, randomised clinical medical trial, comparing the safety and efficacy of endovascular coil treatment and surgical clipping for the treatment of brain aneurysms. The study began in 1994. The first results were published in The Lancet in 2002, and the 10-year data were published again in The Lancet in early September 2005. A total of 2,143 study participants were mostly drawn from U.K. hospitals with the rest drawn from North American and European hospitals. The study found superior results with endovascular coil treatment compared to surgical clipping. However, subsequent studies have questioned this conclusion. The study was criticised by many clinicians and not well accepted by surgeons. Primary criticisms were related to the study's generalisability and the long-term prognosis of coil embolisation.

Study design and results

ISAT sought to measure outcomes of cerebral aneurysm patients at 2 and 12 months using a type of a Rankin scale. The study was prematurely terminated in 2002 after the oversight committee determined there was increased morbidity with surgical clipping compared to endovascular coiling.

Criticism

ISAT was criticised on several factors related to the randomization of the patient population. The patient population was on average younger, and the majority had aneurysms under 10 mm and in anterior circulation. The randomized patient population in the ISAT was younger on average than the population of subarachnoid hemorrhage patients in the U.S. and Japan. In response to these criticisms, a facility that participated in ISAT compared the clinical outcomes of their patients who were not selected for the study to those who were. They reported similar outcomes to the ISAT.

Subsequent analysis

Although the initial ISAT analysis appeared to favor endovascular coiling over microsurgical clipping, subsequent meta-analysis have questioned that conclusion finding higher incidences of recurrence. A large meta-analysis from Johns Hopkins University published in Neurosurgery concluded that "there is no clear consensus in these two studies or in the 45 observational studies included." Updated data from the ISAT group in March 2008 shows that the higher aneurysm rate of recurrence is also associated with a higher re-bleeding rate, given that the re-bleed rate of coiled aneurysms appears to be 8 times higher than that of aneurysms treated with surgical clipping in this study. The ISAT authors conclude that "when treating ruptured cerebral aneurysms, the advantage of coil embolization over clip ligation cannot be assumed for patients younger than 40 years old." Other studies have directly questioned the ISAT's conclusions. This conclusion is based on a number of methodological assumptions itself and other authors have cautioned about extending it to other patient populations. It appears that although endovascular coiling is associated with a shorter recovery period as compared to surgical clipping, it is also associated with a significantly higher recurrence rate after treatment. The long-term data for unruptured aneurysms are still being gathered.