International Subarachnoid Aneurysm Trial
Encyclopedia
The International Subarachnoid Aneurysm Trial (ISAT) was a large multicentre, prospective randomised
clinical medical trial
, comparing the safety and efficacy of endovascular coil
treatment and surgical clipping for the treatment of ruptured 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. 2,143 study participants were mostly drawn from U.K.
hospitals with the rest drawn from North American and European hospitals.
The study found better results with endovascular coil treatment compared to surgical clipping. The study was criticised by many clinicians and not well accepted by surgeons. Primary criticisms were related to the study's patient population's generalisability to the wider population, and the long term prognosis of coil embolisation.
patients at 2 and 12 months using a type of a Rankin scale. The study was halted and too no new patients in 2002 after the oversight committee found increased morbidity with clipping over endovascular coiling.
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 that were not selected for the study to those that were. They reported finding outcomes similar to the ISAT.
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 rebleeding rate, given that the rebleed rate of coiled aneurysms appears to be 8 times higher than that of clipping treated aneurysms 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 < 40 years old." Other subsequent studies have questioned the ISAT's conclusions directly. 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 aneurysm
s are still being gathered.
Randomization
Randomization is the process of making something random; this means:* Generating a random permutation of a sequence .* Selecting a random sample of a population ....
clinical medical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
, comparing the safety and efficacy of endovascular coil
Endovascular coiling
Endovascular coiling, or endovascular emobilization, is a surgical treatment for cerebral aneurysms. It was developed in 1991 by Guido Guglielmi at UCLA. It is one of two surgical treatments for aneurysms, the other being surgical clipping.-Procedure:...
treatment and surgical clipping for the treatment of ruptured brain aneurysms. The study began in 1994. The first results were published in The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
in 2002, and the 10 year data were published again in The Lancet in early September 2005. 2,143 study participants were mostly drawn from U.K.
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
hospitals with the rest drawn from North American and European hospitals.
The study found better results with endovascular coil treatment compared to surgical clipping. The study was criticised by many clinicians and not well accepted by surgeons. Primary criticisms were related to the study's patient population's generalisability to the wider population, and the long term prognosis of coil embolisation.
Study design and results
ISAT sought to measure outcomes of cerebral aneurysmCerebral aneurysm
A cerebral or brain aneurysm is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel.- Signs and symptoms :...
patients at 2 and 12 months using a type of a Rankin scale. The study was halted and too no new patients in 2002 after the oversight committee found increased morbidity with clipping over endovascular coiling.
Criticism
ISAT was criticised on a number of factors, many 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 hemorrhageSubarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
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 that were not selected for the study to those that were. They reported finding outcomes similar 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 John Hopkins University published in NeurosurgeryNeurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
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 rebleeding rate, given that the rebleed rate of coiled aneurysms appears to be 8 times higher than that of clipping treated aneurysms 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 < 40 years old." Other subsequent studies have questioned the ISAT's conclusions directly. 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
Recurrence
Recurrence and recurrent may refer to:*Recurrence relation, an equation which defines a sequence recursively*Poincaré recurrence theorem, Henri Poincaré's theorem on dynamical systems...
rate after treatment. The long-term data for unruptured aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
s are still being gathered.