Arrhythmia Normal Limits Combined Holter/12 Lead ECG Analysis
Jose Vicente, PhD (FDA)
Christine Garnett, PharmD (FDA)
Norman Stockbridge, MD, PhD (FDA)
Cindy L. Green, PhD (Duke Health)
To determine the incidence and variability of various arrhythmias during continuous ECG recordings in healthy adult clinical research volunteers
CSRC Prevention of Sudden Cardiac Death in the Young: National Cardiac Screening Warehouse Pilot Study
Salim Idriss, MD, PhD (Duke Health)
To develop and implement a uniform collection of a core-screening dataset
To demonstrate feasibility of data collection comparing paper and electronic methods and feasibility of long-term outcome collection
CiPA and Cardiac Safety
Philip Sager,MD, FACC, FAHA, FHRS (Sager Consulting)
Mitchell Krucoff, MD (Duke Health)
Sunil Rao, MD (Duke Health)
Marc Samsky, MD (Duke Health)
Restricted Mean Survival Time (RMST) Statistical Analysis Approach for Analyzing Cardiovascular Outcomes Trials
David Manner, PhD and Mary Jane Geiger, MD, PhD
To evaluate the utility of the RMST method (vs traditional HR) in diabetes CVOTs as RMST considers both events and exposure
CSRC/Drug Information Association (DIA) Collaboration: Real World Evidence & CV Safety Educational Curriculum
Mary Jane Geiger, MD, PhD
To educate physicians with regards to key design elements and critical interpretation of real-world evidence studies
CSRC IQ – CSRC Waveform Data Share Program
Borje Darpo, MD, PhD
Will allow other ECG extraction and measurement techniques to be tested on the same waveforms; Waveforms and clinical data in sufficient detail will be shared to allow blinded ECG measurements
Sensitivity and Specificity of New Cardiac Safety Tools for Identifying Effect of Moxi in Healthy Individuals and Their Comparison with Previously Published Data.
Sam George, MD; Cindy Green, PhD; Paul Kligfield, MD, FACC
Proof of Concept Project: QT Analysis of ECG Warehouse Data
Cindy Green, PhD; Paul Kligfield, MD, FACC
Small but statistically significant group differences in mean interval and duration measurements and means of individual absolute differences exist among automated algorithms of widely used, current generation digital electrocardiographs. Measurement differences, including QRS duration and the QT interval, are greatest for the most abnormal ECGs.
The small differences found help investigators and clinicians put a variety of individual and population ECG findings in perspective, with an understanding that specific ECG methodology has the potential to systematically affect test outcomes, regardless of the relative accuracy of individual algorithms
Laura Mauri, M.D.,
Dean J. Kereiakes, M.D.
Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others.
Trans-radial Arteriotomy for Percutaneous Coronary Intervention and Rheologic Drug Safety (Completed) and Trial “Study of Access site For Enhancing Percutaneous Coronary Intervention for Women” (SAFE-PCI for Women)
Sunil Rao, MD
Connie Hess, MD
Compared with access via the femoral artery, radial access did not significantly reduce bleeding or vascular complications in women undergoing percutaneous coronary intervention (PCI) in the SAFE-PCI (Study of Access Site for Enhancement of PCI for Women) trial. However, in a larger sample size of women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding or vascular complications.
A-fib Ablation Registry – SAFARI (Transferred to ACC)
Peter Kowey, MD
Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI.
Cardiovascular Case Report Forms for use in non-cardiovascular clinical trials
Mary Beth Sabol, MD
John Finkle, MD
The CSRC has developed a set of targeted follow-up questions intended for use in clinical trials for non-cardiovascular (non-CV) medical products. The purpose of these questions is to collect information on cardiovascular (CV) events that occur during non-CV outcome trials. Various stakeholders (members of industry, academia, and regulatory authorities) developed these forms to be streamlined and used by non-cardiologists. These forms are not intended for use in CV outcomes trials since there are other sources of targeted follow-up questions that are more detailed and designed for those particular studies.
CiPA and Cardiac Safety
The Comprehensive In Vitro Proarrhythmia Assay (CiPA) effort will substantially evolve the preclinical and clinical proarrhythmia assessment of new chemical entities. At its simplest levels, more comprehensive channel-screening efforts could be implemented early in drug discovery using automated patch-clamp techniques, with the resulting data used to assess proarrhythmic risk using in silico APD reconstructions. Such data could be used for candidate selection as well as to guide further testing.
It is encouraging that elements of the CiPA are already being used in early drug discovery (for example, increasing the number of ionic currents being interrogated and using stem cell cardiomyocytes) as well as guiding early medicinal chemistry efforts, refining early hazard identification, and potentially impacting clinical development. Such efforts should reduce the automatic exclusion of IKr-blocking drugs from early drug discovery. It is anticipated that the commercial costs for such services would be substantially reduced as these efforts are implemented.
Academicians, clinicians and regulators who are familiar with clinical QT studies, mechanisms of proarrhythmia, drug safety assessments, and regulatory submissions are working together under the auspices of the CiPA Steering Committee, Cardiac Safety Research Consortium, HESI, FDA, SPS, EMA, Health Canada, Japan NIHS, and PMDA on this effort. For more information and updates, please contact us at firstname.lastname@example.org.
As part of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) Steering Team, representatives from CSRC attend team meetings to discuss project milestones and serve as liaisons between work streams and stakeholders. Click here for recent updates from the team.