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

Condition(s) targeted: Atrial Fibrillation

Intervention: Intra-Cardiac Echocardiography guided Cardioversion (Device)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: EP MedSystems

Official(s) and/or principal investigator(s):
Sanjeev Saksena, MD, FACC, Study Chair, Affiliation: Professor, UMDNJ-RWJ Medical School

Overall contact:
Ravi S. Mitruka, MBBS, MPH, Phone: (856)366-7156, Email: rmitruka@epmedsystems.com

This is a sequential phase 1 and phase 2 study to evaluate the efficacy of intracardiac echocardiography to detect septal and left atrial pathology as compared to transesophageal echocardiography (Phase 1) and its value in a management strategy for immediate cardioversion during cardiac catheterization procedures in patients with atrial fibrillation as compared to a conventional strategy delaying cardioversion till full anticoagulation is established for a three weeks (Phase 2). Phase 1 will enroll 100 patients at 12 centers; these patients will be undergoing clinically indicated TEE & cardiac catheterization procedures. After review of Phase 1 results by an independent DSMB & the investigators that establish efficacy of ICE, Phase 2 will be initiated. Phase 2 will enroll 300 patients in 15 centers; these patients with atrial fibrillation will be undergoing clinically indicated cardiac catheterization procedures and have a clinical indication for cardioversion. Patients will be randomized to ICE guided cardioversion strategy or a conventional strategy employing three weeks of full anticoagulation before cardioversion. ICE imaging will be used to identify a low risk group for immediate cardioversion. A composite primary study endpoint that will include mortality and major morbidity including stroke and bleeding complications will be used.

This study will examines two hypotheses in AF patients undergoing invasive cardiac procedures:

Hypothesis 1: That ICE has comparable efficacy to TEE in visualization of left atrial pathology or septal defects that can predispose patients to stroke. This will be evaluated during the Phase I component of the study.

Hypothesis 2: That ICE can identify low risk patients in whom immediate cardioversion during the procedure is safe and comparably effective to electrical cardioversion performed based on a conventional strategy of a minimum of 3 weeks of preceding anticoagulation therapy. Low risk patients are expected to have an acceptably low incidence rate of stroke, transient ischemic attack (TIA), peripheral embolism, and major hemorrhagic events following electrical cardioversion. This will be evaluated during the Phase II component of the study, after the Phase I objective is achieved.

Official title: A Sequential Phase I - Phase II Pilot Study to Compare Cardiac Imaging Capabilities of ICE With TEE Followed by a Randomized Comparison of ICE Guided Cardioversion With Conventional Cardioversion Strategy in Patients With Atrial Fibrillation

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Composite incidence of -

Stroke

Transient Ischemic Attack

Peripheral Embolism

Major hemorrhagic bleeding

Secondary outcome:

Prevalence of thrombi or spontaneous contrast detected by ICE,

Time to cardioversion following randomization

Minor bleeding events

Death and major procedure related complications (other than the primary endpoints)

Number of hospitalizations.

Quality of life

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Inclusion Criteria for the Phase I Component

1. Patients with spontaneous AF

2. Patients with or without structural Heart Disease.

3. Men or Women aged 18 years or older.

4. Patients undergoing an invasive catheterization procedure including right heart catheterization.

5. Patients who give an informed consent for participation in the study.

6. Patients who have undergone a trans-thoracic echocardiogram within the last 14 days showing absence of intracardiac thrombi.

7. Patients who have undergone a trans-esophageal echocardiogram within the last 48 hours.

Inclusion Criteria for the Phase II Component

1. Patients with spontaneous AF

2. Patients with or without structural Heart Disease.

3. Men or Women aged 18 years or older.

4. Patients undergoing an invasive catheterization procedure including right heart catheterization.

5. Patients who give an informed consent for participation in the study.

6. Patients who have undergone a trans-thoracic echocardiogram within the last 14 days showing absence of intracardiac thrombi.

Exclusion Criteria:

Exclusion Criteria for the Phase I Component

1. Patients in whom placement of an ICE catheter for adequate atrial visualization is technically not feasible.

2. Women of child bearing potential, in whom pregnancy cannot be excluded.

3. Patients with any medical condition or social circumstance, which in the opinion of the investigator, would make the patient’s successful completion of the study doubtful

Exclusion Criteria for the Phase II Component 1. Patients anticoagulated for > 7 days. 2. Patients who have had a cardioembolic event within the last 1-month. 3. Patients requiring urgent cardioversion due to hemodynamic instability. 4. Patients in whom placement of an ICE catheter for adequate atrial visualization is technically not feasible. 5. Patients with contraindications for Warfarin. 6. Women of child bearing potential, in whom pregnancy cannot be excluded. 7. Patients who need anticoagulation withdrawn due to an elective procedure 8. Patients with any medical condition or social circumstance, which in the opinion of the investigator would make the patient’s successful completion of the study doubtful.

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Ravi S. Mitruka, MBBS, MPH, Phone: (856)366-7156, Email: rmitruka@epmedsystems.com

Erasmus University Medical Center, Rotterdam 2040-3000CA, Netherlands; Recruiting
Petter Janse, Phone: (10) 4632700, Email: p.janse@erasmusmc.nl
Luc Jordaens, M.D., Principal Investigator

Mayo Clinic, Jacksonville, Florida 32224, United States; Recruiting
Nathaniel Benson, CRC, Phone: 904-953-7991, Email: benson.nathaniel@mayo.edu
Kristin Steinbrecker, Phone: (904) 953-7536
Fred M Kusumoto, M.D., Principal Investigator

University of Chicago - Center for Advanced Medicine, Chicago, Illinois 60637, United States; Recruiting
Al McAuley, Phone: 773-702-5877, Email: amcauley@medicine.bsd.uchicago.edu
Bradley P. Knight, M.D., Principal Investigator

Carle Clinic, Urbana, Illinois 61801, United States; Recruiting
Kelly Rice, R.N., Phone: 217-326-0058, Email: Kelly.rice@carle.com
Abraham Kocheril, M.D., Principal Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Michael Sullivan, R.N, Phone: 216-445-6883, Ext: 29402, Email: sullivm4@ccf.org
Andre Natale, M.D., Principal Investigator

Aurora Sinai Medical Center / St. Lukes Medical Center, Milwaukee, Wisconsin 53215, United States; Recruiting
Anthony Chambers, R.N., Phone: 414-385-2565, Email: achamber@hrtcare.com
Jasbir S. Sra, MD, FACC, Principal Investigator

Related publications:

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Lin SL, Hsu TL, Liou JY, Chen CH, Chang MS, Chiang HT, Chen CY. Usefulness of transesophageal echocardiography for the detection of left atrial thrombi in patients with rheumatic heart disease. Echocardiography. 1992 Mar;9(2):161-8.

Castello R, Pearson AC, Labovitz AJ. Prevalence and clinical implications of atrial spontaneous contrast in patients undergoing transesophageal echocardiography. Am J Cardiol. 1990 May 1;65(16):1149-53.

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Starting date: March 2005
Ending date: March 2007
Last updated: January 23, 2006