The rationale and design of the Shockless IMPLant Evaluation (SIMPLE) trial: A randomized, controlled trial of defibrillation testing at the time of defibrillator implantation Jeff S. Healey, MD, MSc, a Stefan H. Hohnloser, MD, b Michael Glikson, MD, c Joerg Neuzner, MD, d Xavier Viñolas, MD, e Philippe Mabo, MD, f Josef Kautzner, MD, g Gilles O'Hara, MD, h Liselot Van Erven, MD, i Frederick Gadler, MD, j Ursula Appl, BSBME, k and Stuart J. Connolly, MD a Ontario, and Quebec City, Canada; Frankfurt, and Kassel, Germany; Tel Hashomer, Israel; Barcelona, Spain; Rennes, France; Praha, Czech Republic; Leiden, The Netherlands; Stockholm, Sweden; and Brussels, Belgium Defibrillation testing (DT) has been an integral part of defibrillator (implantable cardioverter defibrillator [ICD]) implantation; however, there is little evidence that it improves outcomes. Surveys show a trend toward ICD implantation without DT, which now exceeds 30% to 60% in some regions. Because there is no evidence to support dramatic shift in practice, a randomized trial is urgently needed. The SIMPLE trial will determine if ICD implantation without any DT is noninferior to implantation with DT. Patients will be eligible if they are receiving their first ICD using a Boston Scientific device (Boston Scientific, Natick, MA). Patients will be randomized to DT or no DT at the time of ICD implantation. In the DT arm, physicians will make all reasonable efforts to ensure 1 successful intraoperative defibrillation at 17 J or 2 at 21 J. The first clinical shock in all tachycardia zones will be set to 31 J for all patients. The primary outcome of SIMPLE will be the composite of ineffective appropriate shock or arrhythmic death. The safety outcome of SIMPLE will include a composite of potentially DT-related procedural complications within 30 days of ICD implantation. Several secondary outcomes will be evaluated, including all-cause mortality and heart failure hospitalization. Enrollment of 2,500 patients with 3.5-year mean follow-up will provide sufficient statistical power to demonstrate noninferiority. The study is being performed at approximately 90 centers in Canada, Europe, Israel, and Asia Pacific with final results expected in 2013. (Am Heart J 2012;164:146-52.) Randomized trials have clearly demonstrated that the implantable cardioverter defibrillator (ICD) improves survival in patients with left ventricular systolic dysfunc- tion 1 and in those with a history of ventricular arrhythmias. 2 In all of these trials, 1,3 ICD implantation was conducted with some form of intraoperative evaluation of defibrillation efficacy. Thus, the proven benefits of ICD therapy should only be generalized to patients in whom the ICD is implanted with defibrillation testing (DT). Conventional DT, with induction of ventricular fibrilla- tion (VF), permits clinicians to confirm the adequacy of all lead connections, to ensure adequate sensing of VF, and to confirm that the ICD can terminate VF, typically at energies below the maximum output of the ICD. 4,5 However, as ICD technology has matured, the likelihood of successful defibrillation with the initial ICD configura- tion is now N 95%. 5-7 Furthermore, the efficacy of clinical shocks is N 90% and does not seem to differ between patients who had DT and those who did not. 5,7 At the same time, several large registries have demonstrated that DT is associated with infrequent but potentially serious complications, including stroke and death. 8,9 Finally, recent information suggests that ICD shocks could possibly increase the rate of heart failure events. 10-12 The uncertainty regarding the balance of risks and benefits of DT has led some to question the routine conduct of DT at the time of ICD implantation. 13,14 Despite a lack of evidence supporting the safety of ICD From the a Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, b J.W. Goethe University, Frankfurt, Germany, c Sheba Medical Centre, Tel Hashomer, Israel, d Klinikum Kassel, Kassel, Germany, e Hospital de Sant Pau, Barcelona, Spain, f Centre Hospitalier Universitaire and Inserm U 1099, Rennes, France, g Institute for Clinical and Experimental Medicine (IKEM), Praha, Czech Republic, h Universite Laval, Quebec City, Canada, i Leiden University Medical Centre, Leiden, The Netherlands, j Karolinska Hospital, Stockholm, Sweden, and k Boston Scientific, Brussels, Belgium. Submitted February 23, 2012; accepted May 6, 2012. Reprint requests: Jeff S. Healey, MD, MSc, Room C3-121, DBCVSRI Building, Hamilton Health Sciences, General Site, 237 Barton St. East, Hamilton, Ontario, Canada, L8L 2X2. E-mail: Jeff.Healey@phri.ca 0002-8703/$ - see front matter © 2012, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2012.05.007