Intra-Cardiac Echocardiography Guided Cardioversion to Help Interventional Procedures (ICE-CHIP) Study

The presence of intra-atrial thrombi or their precursors with their propensity for systemic
embolism or the presence of interatrial septal defects are major concerns for patients with
atrial fibrillation (AF) undergoing cardioversion. Transesophageal echocardiography (TEE)
has been demonstrated to be a sensitive tool to detect septal defects, left atrial thrombi
and spontaneous echo contrast (1, 2,3). The ACUTE trial documented that TEE based exclusion
of intra cardiac thrombi, smoke or spontaneous echo contrast can facilitate safe immediate
cardioversion in patients with AF. (4) This trial demonstrated comparable risk of embolic
events with a TEE- based strategy to identify low risk patients for immediate cardioversion
when compared to a conventional strategy of 3 weeks of anticoagulation before cardioversion.

The recognition of systemic thromboembolism as a significant potential complication of
cardioversion during interventional cardiology procedures in patients with AF has stimulated
interest in the clinical evaluation of catheter based intra cardiac echocardiography (ICE).
Initial experience with intra cardiac phased –array imaging has demonstrated the efficacy
and feasibility of this technology for intracardiac application and its capability in high
resolution imaging of endocardial structures. (5) In the recent times, the utility of this
imaging modality in various interventional procedures has been investigated and its
effectiveness in visualizing left atrial thrombi during ablative procedures has been
demonstrated in observational studies. (6 -11) However, a prospective multicenter
comparative study of these two imaging techniques is unavailable. Should ICE provide
comparable imaging capabilities to TEE, the value of ICE guided cardioversion during
invasive procedures can also then be systematically studied during a prospective multicenter
clinical study.

The ICE CHIP study is a prospective open label randomized multi-center investigation
performed in two phases designed to initially compare two distinct imaging modalities
(Phase 1) and subsequently two different strategies (ICE guided Cardioversion and
Conventional) in the management of AF in patients undergoing invasive cardiac procedures in
whom electrical cardioversion is indicated (Phase 2).

In Phase I, each patient will be imaged by TEE & ICE and a core echo laboratory will perform
a blinded comparison of the two imaging modalities.

In Phase II, patients will be randomized to one of the two treatment groups. Investigators
will be blinded to the method of management for each patient prior to their enrollment into
the study. The composite incidence rate of major cardiac and bleeding complications (stroke,
TIA, peripheral embolism, major hemorrhagic event) will be compared between the two
treatment groups over the duration of the study.

In Phase 1, 100 patients will be enrolled at up to 12 investigational centers in USA &
Europe. Study patients will have clinically indicated a TEE procedure as well as an invasive
cardiac procedure. Recordings from both imaging methods will be analyzed in an independent
and blinded manner at the core laboratory. It is estimated that enrollment will take 3
months.

In Phase 2, a total of 300 patients (3:2 randomization) will be enrolled in the study at up
to 15 investigational sites in USA and Europe. Patients with AF who require electrical
cardioversion will be enrolled into the study. The study will last for 8 weeks for each
subject, with an estimated overall duration of 12 months (8 months enrollment period, 2
months follow-up period, remaining time for close-out) for the study.

The pilot study design was selected in order to evaluate the comparative accuracy of ICE
imaging and TEE as well as the feasibility of ICE guided management of AF. In Phase 1, the
design will ensure that ICE imaging is not inferior to standard TEE for detection of left
atrial pathology. In Phase 2, ICE imaging will be performed in patients prior to immediate
electrical cardioversion to determine if it is equivalent to the conventional management
strategy of electrical cardioversion after anticoagulation for 3 weeks prior to
cardioversion.

Both the Phase I and Phase II studies will be open label. An open label study design is
proposed because it is not possible to blind the clinicians, patients or the sponsor to the
identity of the diagnostic technique in Phase I (ICE vs. TEE) and to management strategy in
Phase II (ICE vs. Conventional Strategy). The ICE and TEE data analysis in the Phase I
component by the core lab will be blinded in so far as the identity of the patient,
investigator and center. In the Phase II study, patient randomization to the treatment
groups will minimize the chance of patient selection bias. An 8-week study duration was
chosen for the Phase II component because most major cardiac and bleeding complications
occur within this period.