Flow diversion in the treatment of aneurysms: a randomized care trial and registry.

OBJECTIVE The Flow Diversion in the Treatment of Intracranial Aneurysm Trial (FIAT) was designed to guide the clinical use of flow diversion, an innovative method to treat intracranial aneurysms, within a care trial and to study safety and efficacy. METHODS FIAT, conducted in 3 Canadian hospitals, proposed randomized allocation to flow diversion or standard management options (observation, coil embolization, parent vessel occlusion, or clip placement), and a registry of non-randomized patients treated with flow diversion. The primary safety outcome was death or dependency (modified Rankin Scale score > 2) at 3 months, to be determined for all patients who received flow diversion at any time. The primary efficacy outcome was angiographic occlusion at 3-12 months combined with an independent clinical outcome. RESULTS Of 112 participating patients recruited between May 2, 2011, and February 25, 2015, 78 were randomized (39 in each arm), and 34 received flow diversion within the registry. The study was halted due to safety concerns. Twelve (16%) of 75 patients (95% CI 8.9%-26.7%) who were allocated to or received flow diversion at any time were dead (n = 8) or dependent (n = 4) at 3 months or more, crossing a predefined safety boundary. Death or dependency occurred in 5 (13.2%) of 38 patients randomly allocated and treated by flow diversion (95% CI 5.0%-28.9%) and in 5 (12.8%) of 39 patients allocated to standard treatment (95% CI 4.8%-28.2%). Efficacy was below expectations of the trial hypothesis: 16 (42.1%) of 38 patients (95% CI 26.7%-59.1%) randomly allocated to flow diversion failed to reach the primary outcome, as compared with 14 (35.9%) of 39 patients allocated to standard treatment (95% CI 21.7%-52.9%). CONCLUSIONS Flow diversion was not as safe and effective as hypothesized. More randomized trials are needed to determine the role of flow diversion in the management of aneurysms. Clinical trial registration no.: NCT01349582 (clinicaltrials.gov).

[1]  K. Fargen,et al.  Review of reported complications associated with the Pipeline Embolization Device. , 2012, World neurosurgery.

[2]  S. Tjoumakaris,et al.  Flow diversion for complex middle cerebral artery aneurysms , 2014, Neuroradiology.

[3]  J. Mocco,et al.  Utilization of Pipeline embolization device for treatment of ruptured intracranial aneurysms: US multicenter experience , 2014, Journal of NeuroInterventional Surgery.

[4]  D. Kallmes,et al.  Periprocedural and mid-term technical and clinical events after flow diversion for intracranial aneurysms , 2014, Journal of NeuroInterventional Surgery.

[5]  A. Weill,et al.  In Vitro Reproduction of Device Deformation Leading to Thrombotic Complications and Failure of Flow Diversion , 2013, Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences.

[6]  F Guilbert,et al.  Flow Diversion in Aneurysms Trial: The Design of the FIAT Study , 2011, Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences.

[7]  A. Fox,et al.  Bioactive versus Bare Platinum Coils in the Treatment of Intracranial Aneurysms: The MAPS (Matrix and Platinum Science) Trial , 2014, American Journal of Neuroradiology.

[8]  J. Mocco,et al.  Patients Prone to Recurrence after Endovascular Treatment: Periprocedural Results of the PRET Randomized Trial on Large and Recurrent Aneurysms , 2014, American Journal of Neuroradiology.

[9]  J. Wardlaw,et al.  Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial , 2011, The Lancet.

[10]  A. Weill,et al.  Uncertainty and Agreement Regarding the Role of Flow Diversion in the Management of Difficult Aneurysms , 2015, American Journal of Neuroradiology.

[11]  M. Sluzewski,et al.  Flow Diverters for Unruptured Internal Carotid Artery Aneurysms: Dangerous and Not Yet an Alternative for Conventional Endovascular Techniques , 2013, American Journal of Neuroradiology.

[12]  David F. Kallmes,et al.  Endovascular Treatment of Intracranial Aneurysms With Flow Diverters: A Meta-Analysis , 2013, Stroke.

[13]  A. Bonafe,et al.  EVIDENCE Trial: design of a phase 2, randomized, controlled, multicenter study comparing flow diversion and traditional endovascular strategy in unruptured saccular wide-necked intracranial aneurysms , 2014, Neuroradiology.

[14]  T E Darsaut,et al.  Aneurysm Rupture after Endovascular Flow Diversion: The Possible Role of Persistent Flows through the Transition Zone Associated with Device Deformation , 2013, Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences.

[15]  S. Tjoumakaris,et al.  Comparison of Flow Diversion and Coiling in Large Unruptured Intracranial Saccular Aneurysms , 2013, Stroke.

[16]  Adnan H Siddiqui,et al.  Panacea or problem: flow diverters in the treatment of symptomatic large or giant fusiform vertebrobasilar aneurysms. , 2012, Journal of neurosurgery.

[17]  R. Blanc,et al.  Flow Diverters at and Beyond the Level of the Circle of Willis for the Treatment of Intracranial Aneurysms , 2012, Stroke.

[18]  T. Masaryk,et al.  Posterior circulation flow diversion: a single-center experience and literature review , 2014, Journal of NeuroInterventional Surgery.

[19]  Flow Diversion versus Traditional Endovascular Coiling Therapy: Design of the Prospective LARGE Aneurysm Randomized Trial , 2014, American Journal of Neuroradiology.

[20]  S. Tjoumakaris,et al.  Extending the Indications of Flow Diversion to Small, Unruptured, Saccular Aneurysms of the Anterior Circulation , 2014, Stroke.

[21]  D. Altman,et al.  Pragmatic trials can be designed as optimal medical care: principles and methods of care trials. , 2014, Journal of clinical epidemiology.

[22]  I. Saatci,et al.  Treatment of Intracranial Aneurysms Using the Pipeline Flow-Diverter Embolization Device: A Single-Center Experience with Long-Term Follow-Up Results , 2012, American Journal of Neuroradiology.

[23]  A. Kühn,et al.  Flow diverter stents for unruptured saccular anterior circulation perforating artery aneurysms: safety, efficacy, and short-term follow-up , 2014, Journal of NeuroInterventional Surgery.

[24]  A. Fox,et al.  Cerecyte Coil Trial: Angiographic Outcomes of a Prospective Randomized Trial Comparing Endovascular Coiling of Cerebral Aneurysms With Either Cerecyte or Bare Platinum Coils , 2012, Stroke.

[25]  Min S. Park,et al.  Critical assessment of complications associated with use of the Pipeline Embolization Device , 2014, Journal of NeuroInterventional Surgery.

[26]  Efficacy and Safety of Flow Diversion for Paraclinoid Aneurysms: A Matched-Pair Analysis Compared with Standard Endovascular Approaches , 2012, American Journal of Neuroradiology.

[27]  D. Roy,et al.  Fatal arterial rupture during angioplasty of a flow diverter in a recurrent, previously Y-stented giant MCA bifurcation aneurysm , 2016, Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences.

[28]  Adnan H Siddiqui,et al.  Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. , 2013, Radiology.

[29]  R. Sarabia,et al.  Flow-diverter devices for intracranial aneurysms: systematic review and meta-analysis. , 2013, Neurosurgery.

[30]  A Whitehead,et al.  Stopping rules for phase II studies. , 2001, British journal of clinical pharmacology.

[31]  S S Ellenberg,et al.  Randomized consent designs for clinical trials: an update. , 1992, Statistics in Medicine.

[32]  C. Oppenheim,et al.  Intracranial Aneurysms: Recurrences More than 10 Years after Endovascular Treatment-A Prospective Cohort Study, Systematic Review, and Meta-Analysis. , 2015, Radiology.

[33]  Chalmers Tc.  Randomize the first patient , 1977 .

[34]  C. Gandhi,et al.  The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms Trial , 2012 .