Every year an estimated 30,000 persons in the United States will experience rupture of an intracranial aneurysm resulting in subarachnoid hemorrhage (SAH), resulting in significant functional, social, and economic consequences. Almost half of the patients will survive the first year following SAH; more than half will not.
Until recently, surgical clipping to obliterate the aneurysm and reduce the risk of subsequent rupture has been the sole treatment option. Now with the recent development of endovascular treatment using Guglielmi detachable coils, two options for treatment of intracranial aneurysms are available.
A study comparing the efficacy of endovascular to surgical treatment of aneurysms was recently completed. The International Subarachnoid Aneurysm Trial (ISAT), involving centers located predominantly in Europe, reported a reduction in death and disability one year after treatment for patients with ruptured intracranial aneurysms who had undergone endovascular coiling compared to those who were treated with surgical clipping.
To provide a more in-depth comparison between the two treatment modalities and to illuminate the efficacy and associated risks of each, another trial is being planned: the North American Trial for Unruptured and Ruptured Aneurysms (NATURE), a prospective, multicenter study. The NATURE group, led by principal investigator L.N. Hopkins, MD, and Adnan I. Qureshi, MD, was formed approximately two years ago. The group includes nominated representatives from the AANS/CNS Section on Cerebrovascular Surgery: Robert E. Harbaugh, MD, Marc R. Mayberg, MD, Robert H. Rosenwasser, MD, Robert F. Spetzler, MD, and Philip E. Stieg, MD. In addition to neurosurgery, interventional neuroradiology is represented through members of the American Society of Interventional and Therapeutic Neuroradiology: John D. Barr, MD, Jacques E. Dion, MD, and Robert W. Hurst, MD.
During the past two years the NATURE group met several times to identify essential components of the study. The decision was made to limit the study to patients with ruptured aneurysms, excluding patients with unruptured aneurysms. The biggest challenge was developing a design that ensured the objective selection of patients with the least amount of investigator-to-investigator variability. The prime concern raised by experienced investigators was the possibility that most patients would not be randomized in the study, but rather treated outside the protocol. Another area of concern was ensuring that the time frame for post-treatment follow-up was of sufficient length to accurately evaluate the sustained benefit of endovascular or surgical treatment.
In light of these concerns, the strategies considered in the trial design included randomizing all SAH patients presenting to the study centers, and performing cerebral angiography for all treated patients at five years. In September 2002 Drs. Hopkins, Qureshi, Dion, Harbaugh, and Stieg discussed these strategies with a group from the National Institute of Neurological Disorders and Stroke (NINDS) and John R. Marler, MD, associate director for clinical trials at NINDS. The approach of upfront randomization eventually was abandoned because of the possibility of inducing a large heterogeneity in the randomized population. Another strategy presently under consideration is the independent adjudication of all randomized and nonrandomized patients.
In the past few months, the Cerebrovascular Section critically reviewed the NATURE study and ultimately endorsed it based on the merit of the concept, and the commitment of the key investigators to work closely with the neurosurgical and interventional communities to develop an objective and unbiased trial. To be successful, however, the NATURE study will require devoted participation from the all neurosurgeons, together with interventional neuroradiologists. Without an intense level of commitment from both groups, any intracranial aneurysm trial may result in an inadequate assessment.
The results of clinical trials such as NATURE can have a profound effect on treatment protocols, reimbursement, and patient outcomes. Therefore, neurosurgeons and interventionalists must critically review the design of any study and participate with complete dedication.
The NATURE study is to be submitted to NINDS on June 1, 2003, for possible funding. Further information regarding the design, participation, and progress of the study can be obtained from Dr. Qureshi ([email protected]) or Dr. Hopkins.
Adnan I. Qureshi, MD, is a member of the Dept. of Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey in Newark, N.J. L.N. Hopkins, MD, is a neurosurgeon at Millard Fillmore Hospital in Buffalo, N.Y.
For Further Information
|