The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED).

Background: The UNTOUCHED study will assess the safety and efficacy of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the most common cohort of patients receiving ICDs. The primary goal is to evaluate the inappropriate shock (IAS)-free rate in primary prevention patients with a reduced ejection fraction (EF) and compare with a historical control of transvenous ICD patients with similar programming. Methods and Results: The UNTOUCHED study is a global, multicenter, prospective, nonrandomized study of patients undergoing de novo S-ICD implantation for primary prevention of sudden cardiac death with a left ventricular EF <= 35%. The primary end point of this trial is freedom from IAS at 18 months. The lower 95% confidence bound of the observed incidence will be compared to a performance goal of 91.6%, which was derived from the IAS rate in MADIT-RIT. The secondary end points are all-cause shock-free rate at 18 months, and system-and procedure-related complication-free rate at 1 month and 6 months. Enrollment of a minimum of 1,100 subjects from up to 200 centers worldwide is planned based on power calculations of the primary and principal secondary end points. Conclusions: This trial will provide important data regarding the rates of inappropriate and appropriate shock therapy in real-world use of the S-ICD in the most common group of patients receiving ICDs.