Control for EU (European Union) Focal Impulse and Rotor Modulation Registry - Topera C-FIRM Registry-
Conditions: Atrial Fibrillation
Sponsor: Abbott Medical Devices

NCT-02407249

 
 
20150217-Rev E 
C-FIRM-02 
Page 3 of 13 
 
 
Synopsis 
Introduction
Atrial fibrillation (AF) is the most common sustained arrhythmia in man, 
and has an increasing population prevalence over time. Treatment is 
aimed at stroke prevention on the one hand, and amelioration of 
symptoms (palpitations, lightheadedness, dyspnea, fatigue) due to the 
arrhythmia. Medical therapy often fails to render a satisfactory 
response for the latter, prompting the search for alternative therapies. 
Surgical and, in the last 15 years, catheter ablation techniques have 
been devised to try to prevent episodes from starting. Groundbreaking 
work by Haïssaguerre showed that premature discharges or rapid 
repeated firing from the pulmonary veins (PVs) could trigger AF 
episodes and that electrical isolation of the PVs could potentially cure 
the patient of AF. PV isolation currently is a painstaking process 
consisting of delivering radiofrequency energy in the left atrium to 
isolate these veins. Such procedures take 3-5 hr to complete 
depending on the complexity of the individual case, and a large 
percentage of patients require a 2nd or even 3rd procedure to achieve 
acceptable antiarrhythmic results. Despite considerable investigative 
effort, the exact pathophysiology of how PV triggers initiate and or 
maintain episodes of AF has been elusive.  
Recently, Narayan et al have developed an algorithm that has been 
licensed for use with a novel mapping technology (RhythmView, 
Topera, Inc, Palo Alto, CA) for analyzing atrial recordings during 
human AF, finding that >95% of cases demonstrate either a rapidly 
spinning rotor (small circuit) or very rapid focal impulse formation. 
Furthermore, they have shown that catheter ablation at these relatively 
circumscribed areas can significantly affect AF, either by substantial 
slowing of the rate or termination (to an atrial tachycardia or sinus 
rhythm). In the CONFIRM (CONventional vs Focal Impulse and Rotor 
Modulation) trial, patients were treated with either conventional 
mapping and ablation (largely PV isolation or PVI) vs ablation of rotors 
or sites of focal impulse formation as designated by the mapping 
algorithm, followed by conventional ablation (PVI). The authors found 
much higher acute and long-term efficacy when focal impulse and 
rotor modulation (FIRM ablation) was used (82.4 vs 44% freedom from 
AF at 24 months post procedure). Although CONFIRM was a 
controlled registry, a randomized evaluation would be warranted. 
 
C-FIRM is a control registry to E-FIRM to track conventional AF 
procedures in terms of clinical usage, handling, and the safety and 
effectiveness for the treatment of symptomatic atrial fibrillation.  There 
will be 10 patients enrolled per participating site in this registry.  
Safety 
endpoint 
 
Safety shall be evaluated both acute and long term. 
 
 

 
 
20150217-Rev E 
C-FIRM-02 
Page 4 of 13 
 
 
Endpoint
Description
Acute success 
Freedom from major adverse events related to 
the procedure within seven days of the 
procedure. 
Long-term 
success 
Freedom from cumulative major adverse events 
related to the procedure (including any repeat 
procedures required) within one year of the initial 
procedure. 
 
Primary Efficacy 
endpoint 
 
Efficacy endpoints are defined in the table below. 
 
Endpoint
Definition
Acute success 
of conventional 
AF ablation 
The acute success of conventional AF ablation is 
defined as elimination of PV triggers.   
Any other site specific AF ablation techniques are 
in discretion of the physicians. 
 
Long term 
success 
Two sequential endpoints will be used for long 
term efficacy after the initial AF ablation 
procedure (only): 
(1) Single Procedure Freedom from AF 
recurrence* at 3 months, and 
(2) Single Procedure Freedom from AF 
recurrence* from 3-12 months after the initial AF 
ablation procedure 
 
*Freedom from AF recurrence is defined as: No 
document episodes of AF >30 sec with conventional 
noninvasive monitoring or, in the case of an cardiac 
implanted electronic device (CIED), <1% AF noted 
overall and no episodes of AF>30 sec. 
 
 
 
 
 
 
 
Registry 
design 
 
The design of the registry is summarized in the table below. 
Item
Description
Design 
This is a registry to assess the safety and 
effectiveness of conventional AF procedures for 
the treatment of symptomatic any type of atrial 
fibrillation. 

 
 
20150217-Rev E 
C-FIRM-02 
Page 5 of 13 
 
 
  
Patient 
population 
 
Subjects eligible for participation in the registry should be in  
accordance to the AF guidelines: 
• Reported incidence of at least two (2) documented episodes of 
symptomatic AF (paroxysmal, persistent or long standing persistent) 
during the three months preceding trial entry (at least one episode 
should be documented by rhythm strip or ECG).  
• Attempt of at least one Class I or III anti-arrhythmia drug with 
failure defined as recurrence of symptomatic AF or adverse 
drug effect resulting in stopping the medication. 
 
Registry
schedule 
The registry visits schedule will follow the standard routine procedure 
of each site . Proposed activities during the visits are described in the 
table below.  Since this is a registry, these are data items that will be 
collected, if available, as consistent and applicable with routine and 
standard clinical care at each site. 
Visit Timing
Description
Procedure and 
immediate 
post-
procedure 
Cardiac ablation procedure (see “Ablation Procedure” for details). 
During the procedure, the patient will be monitored for adverse events.  
Appropriate clinical measures will be taken to treat the adverse event, 
should one occur. 
Seven-Ten 
Days Post 
Procedure 
The following assessments/procedures will be performed: 
• Symptom and rhythm assessment per defined follow up monitoring 
• Follow up to assess for adverse events
Three Months 
Post 
Procedure 
The following assessments/procedures will be performed: 
• Diagnostic 12-lead ECG 
• 48-hr or 72-hr ambulatory continuous ECG monitor (Holter) or CIED 
interrogation, if applicable 
• Symptom and rhythm assessment per defined follow up monitoring 
• Concomitant anti-arrhythmic medications 
• Adverse events 
Sample Size 
Each site will enroll in total 10 consecutive 
conventional (non-FIRM guided) AF patients, 
after having enrolled at least one patient into the 
E-FIRM registry.  
Conventional AF ablation is defined as  
pulmonary vein isolation (PVI) and any addition 
ablation for AF according to the standard routine 
of the center. 
FIRM-guided ablation is defined as ablating FIRM 
identified sources independent of any additional 
ablation. 
Randomization 
The registry is non-randomized but consecutive. 
Investigators 
Up to 2 investigators per site 
Investigative 
sites 
Up to 10 investigative sites within Germany / 
Europe 

 
 
20150217-Rev E 
C-FIRM-02 
Page 6 of 13 
 
Six Months 
Post 
Procedure 
The following assessments/procedures will be performed: 
• Diagnostic 12-lead ECG 
• 48-hr or 72-hr ambulatory continuous ECG monitor (Holter) or CIED 
interrogation, if applicable 
• Symptom and rhythm assessment per defined follow up monitoring  
• Concomitant anti-arrhythmic medications 
• Adverse events 
Twelve 
Months Post 
Procedure 
The following assessments/procedures will be performed: 
• Diagnostic 12-lead ECG 
• 48-hr or 72-hr ambulatory continuous ECG monitor (Holter) or CIED 
interrogation, if applicable 
• Symptom and rhythm assessment per defined follow up monitoring 
• Concomitant anti-arrhythmic medications 
• Adverse events 
 
Ablation 
procedure 
description 
Investigators should follow the routine standard procedure as defined 
by the center. 
Post 
procedure 
rhythm 
monitoring 
 
According to routine and standard procedure of the site preferred 
would be for all subjects without CIED (having AF diagnostic 
algorithms) to  receive a 48 or 72 hour Holter monitor at 3, 6, and 12 
months post-procedure. 
 
AF symptoms should be documented as recurrent within the follow-up 
period, further treatment shall be at the discretion of the physician 
(e.g., drugs, re-ablation, etc.).   
Description
This is a consecutive registry to assess the safety and effectiveness of 
conventional AF procedures for the treatment of symptomatic atrial 
fibrillation. 
Patient 
numbering 
 
Subjects will be assigned consecutive numbers per participating site in 
combination to a site code 
Expertise 
 
In order to participate in this C-FIRM registry, investigators must have 
completed at least one FIRM guided AF ablation. 
 
 

 
                                   
 20150217-Rev E 
C-FIRM-02 
 
Page 7 of 13                                                                      
 
Synopsis 
Registry data 
collection 
detail 
 
Legend: 
 = Data field 
 
 = if applicable 
 
 
 
 
 
Event 
Pre-proc 
Intra-proc 
Discharge 
Day 7-10 
1 month 
3 month 
6 month 
12 month 
Demographics, Medical Hx, Cardiac Dx 
 
 
 
 
 
 
 
 
Lab work (Chemistry, UA, Cardiac 
enzymes, HCG, LFTs) 
 
 
 
 
 
 
 
 
INR (as appropriate on post-ablation f/u) 
 
 
 
 
 
 
 
 
TEE  
 
 
 
 
 
 
 
 
Diagnostic 12-lead ECG 
 
 
 
 
 
 
 
 
Documentation of Symptomatic AF 
 
 
 
 
 
 
 
 
Cardiac meds and any AF interventional 
procedures performed 
 
 
 
 
 
 
 
 
NYHA Class Assessment 
 
 
 
 
 
 
 
 
AF Symptom and rhythm assessment 
per defined follow up monitoring 
 
 
 
 
 
 
 
 
AE review 
 
 
 
 
 
 
 
 
Interrogation of CIED for AF burden  
 
 
 
 
 
 
 
 
48-hr or 72-hr ambulatory continuous 
ECG monitor 
 
 
 
 
 
 
 
 

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 8 of 13 
                 
  
                        
Adverse Events 
Overview
All adverse events (unanticipated and anticipated) must be classified 
as serious or minor. 
Definitions 
 
The table below describes the classifications of adverse events (AE).  
All major adverse events occurring during the registry will be included 
in the safety analysis. 
 
Term
Definition
Serious  
Any adverse event which occurs following use of 
the device and: 
• is life-threatening*; 
• results in permanent impairment of a body 
function or permanent damage to a body 
structure; or 
• necessitates significant intervention, such as 
major surgery, to prevent permanent impairment 
of a body function or permanent damage to a 
body structure; or 
• requires hospitalization or an extended hospital 
stay; or 
• results in moderate transient impairment of a 
body function or transient damage to a body 
structure; or 
• requires intervention such as medication or 
cardioversion* to prevent permanent impairment 
of a body function or damage to a body 
structure**. 
Minor  
Any adverse event that occurs following use of the   
procedure that results in minimal transient 
impairment of a body function or damage to a body 
structure, or which does not require any 
intervention other than monitoring. 
Anticipated  
Anticipated or known possible adverse events 
associated with cardiac electrophysiology 
procedures (see detail listing below in “Anticipated 
AE”) 
 
Term
Definition
Unanticipated 
EU guideline and requirements will be applicable 
 

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 9 of 13 
                 
  
                        
* In this context, the term refers to an event in which the subject was at 
immediate risk of death at the time of the event; it does NOT refer to 
an event that might have caused death if it were more severe. 
** For example, if the occurrence of a “catheter insertion site 
hematoma” or an “AV fistula” requires a blood transfusion and/or 
surgical repair, it should be considered a major adverse event. 
Anticipated 
AE 
 
Anticipated adverse events include: 
 
Description
Description
Discomfort due to insertion/removal of vascular 
sheaths beyond what is normally observed 
 
Ventricular arrhythmia requiring 
defibrillation 
Hemorrhage and/or hematoma at sheath insertion 
requiring evacuation or transfusion  
 
Cardiac tamponade due to perforation 
Extremity weakness, swelling, and/or pain  
 
 
Discomfort and/or damage to the skin, muscles, or 
nerves due to remaining in a supine position for an 
extended period of time. 
 
Nerve injury (diaphragmatic paralysis, 
pyloric spasm, gastric hypomotility) 
Complete AV block  
 
Air embolism 
Nausea /vomiting 
 
Allergic reaction 
Headache different from baseline 
 
Endocarditis 
Hypertension >180 mm Hg systolic (repeated 
measures) 
 
Esophageal-atria fistula 
Hypotension <80 mm Hg systolic (repeated 
measures) 
 
Hemothorax 
Brief “black out” periods 
 
Pericarditis 
Shortness of breath/Dyspnea 
 
Pseudo aneurysm 
Feeling of chest pain, skipped beats, and/or rapid 
heart rate different from baseline 
 
Pulmonary vein stenosis 
Damage to skin from prolonged exposure to x-rays 
 
Radiation injury 
New arrhythmias (not previously documented) 
 
Renal failure form IV contrast 
Arterial injury requiring intervention 
 
Respiratory failure 
Thromboembolism 
 
Stroke/TIA 
Local/systemic infection 
 
Valvular damage 
Pneumothorax 
 
Pleural effusion 
AV fistula 
 
Pulmonary edema 
Thrombophlebitis 
 
Anemia requiring transfusion 
Pulmonary embolism 
 
Vasovagal reaction 
Myocardial infarction 
 
New pericardial effusion >1 cm 
Discomfort and/or damage to the skin, muscles, or 
nerves due to percutaneous access in excess of 
usual  
 
Death (must be reported within the 
regulation of serious adverse 
events) 
Left heart access via trans-septal puncture has 
known potential adverse events of: cardiac 
perforation, cardiac tamponade, and embolic 
events.*   
 
 

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 10 of 13 
                 
  
                        
* Literature reviews have demonstrated that the risk of such events are <1%. 
Mullins, Charles E. “Trans-septal left heart catheterization: Experience with a new 
technique in 520 pediatric and adult subjects.”  Pediatric Cardiology, v. 4, pgs. 239-
246 (1983) 
  
Occurrence
The table below describes actions taken for adverse events that occur 
during and after the procedure. 
 
Timing
Action
Intra-procedure 
If the investigator determines that an adverse 
event occurs while the patient is in the 
electrophysiology lab (before or during the 
procedure), the investigator shall manage the 
patient as he/she would if a similar event 
occurred during a standard EP procedure.   
 
Post-procedure 
Once the patient has left the electrophysiology 
lab, all medical/surgical management will be 
carried out in the standard manner for that 
institution 
 
Reporting 
SAEs, & 
deaths 
Reporting requirements for deaths or other adverse events considered 
to be serious or unanticipated are described in the table below. 
 
Report to
Reporting Requirements
Principal 
Investigative 
Site 
Must be reported according to the rules of the 
respective Ethics Committee  
EC 
Report of the adverse event to the site’s Institutional 
Review Board is the responsibility of the Principal 
Investigator.   
 
The investigator is responsible for reporting such 
events to their EC within 10 working days of 
knowledge of the event. 
 
Adverse events clearly unrelated to the device (e.g., 
broken limb, malignancy) may be reported in 
accordance with institutional requirements and 
recorded on CRFs as appropriate 
 
Details are found in Medical Event Report Form “MERF” below. 
 

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 11 of 13 
                 
  
                        
MERF
The table below describes the information required on the initial and 
final MERF reports. 
 
Information
Initial
Final
Patient registry number 
√ 
√ 
Gender 
√ 
√ 
Date of birth 
√ 
√ 
Date of   procedure 
√ 
√ 
Adverse experience/complication and classification 
(major/minor) 
√ 
√ 
Period of hospitalization (if required) 
√ 
√ 
Investigator’s opinion as to the relationship of 
event/complication to the   device 
√ 
√ 
The disposition of the device (if returned, provide 
date) 
√ 
√ 
Description of the event or problem 
√ 
√ 
Classification of event (anticipated/unanticipated 
and minor/major) 
 
√ 
Date of onset 
 
√ 
Date of resolution 
 
√ 
Date of discovery 
 
√ 
Reporter name, title, and contact information 
 
√ 
Patient outcome 
 
√ 
Treatment or therapy used to treat 
 
√ 
Relevant laboratory tests 
 
√ 
Relevant history, including pre-existing medical 
conditions 
 
√ 
Suspect   device name, part number, and lot 
number 
 
√ 
 
Data Collection 
Data will be entered according to the source document forms into an electronic 
database (online).  
 
 
Statistical Analysis Plan  
 
 

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 12 of 13 
                 
  
                        
Special 
Requirements 
and Procedures 
 
Source 
document 
forms 
A ring binder with one Source Document Form (SDF) could be 
provided to each participating site.  Below are the guidelines for SDF 
completion and conclusion. 
 
Item
Instruction
1 
Data entry via a secure data line to a centralized 
independent database 
2 
Maintain each SDF and all relevant source 
documentation in the appropriate individual notebook. 
3 
Complete SDF or type. 
4 
Cross out erroneous entries with a single line, initial and 
date, and record the correct entry. 
Source 
documents 
 
Copies of pertinent records (i.e., source documents, patient charts, 
laboratory data, etc.) in connection with the registry not included in the 
notebook will be made available on request with due diligence toward 
protecting the privacy of the subject. 
Disclosure of 
data 
 
All information obtained during the conduct of this registry will be 
regarded as confidential.  Manuscripts prepared for publication will be 
submitted to a steering committee/principal investigator, mutually 
agreed upon by participating sites, for review and comments prior to 
submission to the publisher. This condition should not be construed as 
a means of restricting publication but is intended solely to assure 
mutual concurrence regarding data, evaluations, and conclusion, to 
provide an opportunity to share with the investigator any new and/or 
unpublished information of which he/she may be unaware, and to 
assure regulatory compliance of the results presented. 
 
EC 
 
This protocol and the patient consent form will be reviewed and 
approved by the Ethics Committee (EC). 
Informed 
consent 
 
It is the responsibility of the institution to ensure compliance with 
relevant regulation regarding sharing personal health information 
during the course of this research.  Written informed consent is 
required prior to enrollment in the registry.  It is the responsibility of the 
investigator to obtain that consent.   
Acknowledge 
ment 
 
The Principal Investigator understands and acknowledges that any 
industry personnel such as those from Topera without appropriate 
medical training and/or licensure shall not directly participate in the 
procedure.  Such individuals may be present, at the discretion of the 
physician, solely as advisors and/or observers.  Advice shall be 
contained to the operation, function, and/or maintenance of the 
equipment and/or software.  Any and all medical decisions regarding 
patient care and treatment shall solely be the responsibility of the 
Principal Investigator.  

 
                                   
 20150217-Rev E 
 
 
                                                         
 
C-FIRM-02    
Page 13 of 13 
                 
  
                        
Document 
retention 
 
The investigator must retain the registry data for a time period required 
by the current guidelines unless other rules require a longer retention 
period 
 
Additional 
consideration 
The registry procedure will be carried out in a manner consistent with 
local procedure standard and with current contractual agreements 
between each individual site Principal Investigator and their associated 
educational and medical institutions.   
 
The site Principal Investigator shall strictly adhere to clinical standards 
defined by the guidelines of the European and German societies.