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\begin{document}

\title{Rationale and Design of the Lead EvaluAtion for Defibrillation and
Reliability (LEADR) Study: Safety and Efficacy of a Novel ICD Lead
Design}



\author[1]{George Crossley}%
\author[2]{Prashanthan Sanders}%
\author[3]{Paolo De Filippo}%
\author[4]{Khaldoun Tarakji}%
\author[5]{Bert Hansky}%
\author[6]{Maully Shah}%
\author[7]{Pamela Mason}%
\author[8]{Baerbel Maus}%
\author[9]{Keith Holloman}%
\affil[1]{Vanderbilt University Medical Center}%
\affil[2]{Royal Adelaide Hospital Libraries}%
\affil[3]{Aziende Socio Sanitarie Territoriale Papa Giovanni XXIII}%
\affil[4]{Cleveland Clinic}%
\affil[5]{Städtische Kliniken Bielefeld Germany}%
\affil[6]{The Children’s Hospital Philadelphia PA USA}%
\affil[7]{University of Virginia Medical Center}%
\affil[8]{Bakken Research Center Medtronic Inc Maastricht The Netherlands}%
\affil[9]{Medtronic Inc Mounds View Minnesota}%


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  \date{May 27, 2024}


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\begin{abstract}
\textbf{Background:} Implantable cardioverter defibrillators (ICD) are
indicated for primary and secondary prevention of sudden cardiac arrest.
Despite enhancements in design and technologies, the ICD lead is the
most vulnerable component of the ICD system and failure of ICD leads
remains a significant clinical problem. A novel, small diameter,
lumenless, catheter delivered, defibrillator lead was developed with the
aim to improve long term reliability. \textbf{Methods and Results:} The
Lead Evaluation for Defibrillation and Reliability (LEADR) study is a
multi-center, single-arm, Bayesian, adaptive design, pre-market
interventional pivotal clinical study. Up to 60 study sites from around
the world will participate in the study. Patients indicated for a de
novo ICD will undergo defibrillation testing at implantation and
clinical assessments at baseline, implant, pre-hospital discharge, 3
months, 6 months, and every 6 months thereafter until official study
closure. Patients will participate for a minimum of 18 months to
approximately 3 years. Fracture-free survival will be evaluated using a
Bayesian statistical method that incorporates both virtual patient data
(combination of bench testing to failure with in-vivo use condition
data) with clinical patients. The clinical subject sample size will be
determined using decision rules for number of subject enrollments and
follow-up time based upon the observed number of fractures at certain
time points in the study. The adaptive study design will therefore
result in a minimum of 500 and a maximum of 900 patients enrolled.
\textbf{Conclusion:} The LEADR Clinical Study was designed to
efficiently provide evidence for short- and long-term safety and
efficacy of a novel lead design using Bayesian methods including a novel
virtual patient approach.%
\end{abstract}%



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\textbf{Hosted file}

\verb`LEADER Design Paper Draft_JCE_10DEC2021 Final GHC.docx`  available at \url{https://authorea.com/users/451172/articles/551037-rationale-and-design-of-the-lead-evaluation-for-defibrillation-and-reliability-leadr-study-safety-and-efficacy-of-a-novel-icd-lead-design}

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