A Prospective, Multi-Center, Single-Arm, Post Market Study of the MitraClip System for the Treatment of Symptomatic Mitral Regurgitation in China
Phase: NA
Conditions: Mitral Regurgitation
Sponsor: Abbott Medical Devices

 
 
Clinical Investigation Plan Cover Page 
 
 
 
CL1029982 Rev. A 
NCT Number: NCT04259411 
MitraClip China Post-Market Study (PMS) 
Study Document Name: MitraClip China PMS Clinical Investigation Plan 
Date: December 3rd , 2020 
 
Sponsor: 
Abbott Vascular  
3200 Lakeside Drive 
Santa Clara, CA  95054, USA 
 
 
 
Abbott Medical (Shanghai) Co. Ltd. 
Room 402, 4th Floor, Building B,  
No. 169 Taigu Road, Pilot Free Trade Zone 
Shanghai, China 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
Template: 86357 Rev. H 
 
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MitraClip China Post Market Study Clinical Investigational Plan 
 
CRD956-PMS 
 
MitraClip China PMS 
 
A Prospective, Multi-Center, Single-Arm, Post Market Study of the MitraClip System for 
the Treatment of Symptomatic Mitral Regurgitation in China 
 
Version Number 
 
B 
Version Date 
03DEC2020 
 
Planned Number of Sites and Region(s) 
Up to 10 sites in China 
 
Trial Type 
 
Post Market Study (PMS) 
Abbott Medical Expert 
 
Ihsen Merioua 
Sponsor  
Abbott Vascular  
3200 Lakeside Drive, Santa Clara, 
CA  95054, USA 
Authorized Representative in China 
Abbott Medical (Shanghai) Co. Ltd. 
Room 402, 4th Floor, Building B, No. 
169, Taigu Road, China (Shanghai) 
Pilot Free Trade Zone 
Data Monitoring/Data 
Management/Data Analysis 
Abbott Medical (Shanghai) Co. Ltd. 
Room 402, 4th Floor, Building B, No. 
169, Taigu Road, China (Shanghai) 
Pilot Free Trade Zone 
Electronic Data Capture Software 
 
Abbott Oracle Remote Data Capture 
System 
Echocardiographic Core Laboratory 
 
UCSF Echo Core Lab 
505 Parnassus Ave, M318 
San Francisco, CA 94143 
Clinical Investigational Plan Author 
Yunlong (Phil) Zhang, MD, MS 
Clinical Consultant 
 
 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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without the express written consent of Abbott 
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Site Principal Investigator Signature Page 
 
 
Study Title: 
MitraClip China PMS: A Prospective, Multi-Center, Single-Arm, Post 
Market Study of the MitraClip System for the Treatment of 
Symptomatic Mitral Regurgitation in China 
Study Number: 
CRD956-PMS 
Version Number: 
B 
Version Date: 
03DEC2020 
 
 
I have read and agree to adhere to the MitraClip China Post Market Study (PMS) Clinical 
Investigational Plan and all regulatory requirements applicable in conducting this study. 
 
 
Site Principal Investigator 
 
Printed name: 
Signature: 
Date: 
 
 
 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used 
without the express written consent of Abbott 
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Contents 
1 
Introduction ................................................................................................ 7 
 
Background and Rationale ................................................................ 8 
1.1.1 
Background ....................................................................................... 8 
1.1.2 
Rationale for Conducting this Post Market Study ............................ 13 
2 
Study Overview ........................................................................................ 14 
 
Study Objective ............................................................................... 14 
 
Device used in the Study ................................................................ 14 
2.2.1 
Name of the Device ........................................................................ 14 
2.2.2 
Indication for Use ............................................................................ 14 
2.2.3 
Description of the Device ................................................................ 14 
3 
Study Design ............................................................................................ 17 
 
Study Procedure and Follow-up Schedule ...................................... 17 
 
Measures Taken to Avoid and Minimize Bias ................................. 18 
 
Early Termination of the Study ........................................................ 18 
4 
Endpoints ................................................................................................. 19 
 
Primary Endpoints........................................................................... 19 
 
Descriptive Endpoints ..................................................................... 19 
5 
Subject Selection and Withdrawal ............................................................ 21 
 
Subject Population .......................................................................... 21 
 
Subject Recruitment/Screening and Informed Consent .................. 21 
5.2.1 
Subject Recruitment and Screening................................................ 21 
5.2.2 
Informed Consent ........................................................................... 22 
5.2.3 
Special Circumstances for Informed Consent ................................. 23 
 
Eligibility Criteria ............................................................................. 23 
5.3.1 
Eligibility Assessment ..................................................................... 23 
5.3.2 
Inclusion Criteria ............................................................................. 23 
5.3.3 
Exclusion Criteria ............................................................................ 23 
 
Subject Enrollment and Registration ............................................... 24 
 
Subject Withdrawal and Discontinuation ......................................... 24 
 
Number of Subjects ........................................................................ 25 
 
Total Expected Duration of the Clinical Study ................................. 25 
6 
Treatment and Evaluation of Endpoints ................................................... 26 
 
Baseline .......................................................................................... 26 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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6.1.1 
Transthoracic & Transesophageal Echocardiograms to Confirm Subject 
Eligibility .......................................................................................... 26 
6.1.2 
Clinical Assessments ...................................................................... 26 
6.1.3 
12-Lead ECG .................................................................................. 26 
 
Anticoagulation and Antiplatelet ...................................................... 26 
 
Subject Preparation ........................................................................ 27 
 
MitraClip Procedure ........................................................................ 27 
 
Post–MitraClip Procedure ............................................................... 28 
 
Follow-up for All Subjects ............................................................... 29 
 
Additional Follow-up Visits for All Subjects ..................................... 32 
7 
Adverse Events ........................................................................................ 32 
 
Definition ......................................................................................... 32 
7.1.1 
Adverse Event ................................................................................ 32 
7.1.2 
Serious Adverse Event ................................................................... 32 
7.1.3 
Device Deficiency/Device malfunction ............................................ 33 
 
Device Relationship ........................................................................ 33 
 
Adverse Event and Device Deficiency/Device Malfunction Reporting33 
7.3.1 
Adverse Event Reporting ................................................................ 33 
7.3.2 
Device Deficiency/Device Malfunction Reporting ............................ 35 
7.3.3 
Adverse Event Reporting to Regulatory Authorities by the Sponsor35 
8 
Statistical Considerations ......................................................................... 35 
 
Analysis Populations ....................................................................... 36 
8.1.1 
Attempted Procedure Population (AP) ............................................ 36 
8.1.2 
Implanted Population (IP) ............................................................... 36 
 
Statistical Analyses ......................................................................... 36 
8.2.1 
Primary Endpoints Analyses ........................................................... 36 
 
Sample Size Calculations and Assumptions ................................... 37 
 
Time of Analysis ............................................................................. 37 
9 
Direct Access to Source Data/Documents ............................................... 37 
10 
Quality Control and Quality Assurance ..................................................... 37 
 
Selection of Clinical Sites and Investigators ................................... 37 
 
Study Finance and Agreements ...................................................... 38 
 
Protocol Amendments ..................................................................... 38 
 
Training ........................................................................................... 38 
10.4.1 Site Training .................................................................................... 38 
10.4.2 Training Required for the Use of the Device ................................... 39 
 
Monitoring ....................................................................................... 40 
 
Deviations from Protocol ................................................................. 41 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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Quality Assurance Audit .................................................................. 42 
 
Sponsor Auditing ............................................................................ 42 
 
Primary Investigator Responsibilities .............................................. 42 
11 
Data Handling and Record Keeping ......................................................... 42 
 
Protection of Personally Identifiable Information ............................. 43 
 
Data Management Plan .................................................................. 44 
 
Source Documentation ................................................................... 44 
 
Electronic Case Report Form Completion ....................................... 45 
 
Record Retention ............................................................................ 46 
12 
ETHICAL CONSIDERATION ................................................................... 47 
 
Ethics Committee Review and Approval ......................................... 47 
13 
Clinical Study Conclusion ......................................................................... 47 
14 
PUBLICATION POLICY ........................................................................... 47 
15 
RISK ANALYSIS ...................................................................................... 48 
 
Anticipated Clinical Benefits ............................................................ 48 
 
Foreseeable Adverse Events and Anticipated Adverse Device Effects
 
49 
 
Residual Risk Associated with MitraClip System ............................ 49 
 
Risk Associated with Participation in This Study ............................. 50 
 
Possible interaction with Protocol-Required Concomitant Medications
 
50 
 
Steps Taken to Control or Mitigate Risks ........................................ 50 
 
Risk to Benefit Rationale ................................................................. 50 
16 
Appendices .............................................................................................. 52 
 
Appendix I: Abbreviations and Acronyms ....................................... 52 
 
Appendix II: Definitions ................................................................... 54 
 
Appendix III: Transthoracic Echocardiography Acquisition Guidelines 65 
 
Appendix IV: Revision History ......................................................... 71 
 
Appendix V: Protocol Summary ...................................................... 72 
 
Appendix VI: References ................................................................ 75 
 
 
 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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without the express written consent of Abbott 
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Compliance Statement: 
 
The MitraClip China PMS Study will be conducted in accordance with this Clinical 
Investigational Plan, the Declaration of Helsinki and the National Medical Products 
Administration (NMPA) applicable regulations. The most stringent requirements, 
guidelines or regulations must always be followed. The conduct of the study will be 
approved by the appropriate Ethics Committee (EC) of the respective clinical site and as 
specified by local regulations. 
 
This clinical study will be filed in compliance with Regulations on Management of Human 
Genetic Resources of the People’s Republic of China (2019 No. 717) with the Human 
Genetics Resources Administration of China. 
                    
 
 
 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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without the express written consent of Abbott 
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1 
INTRODUCTION  
Mitral regurgitation (MR) is the most common heart valve condition in the world.  MR 
occurs when the mitral valve does not close properly, allowing blood to leak back into the 
upper chamber of the heart.  As a result, the heart may try to pump harder in order to 
compensate for the decrease in blood flow to the rest of the body.  Patients with severe 
MR suffer from debilitating symptoms such as shortness of breath, heart palpitations, 
lightheadedness, and fatigue.  These patients are at risk of poor quality of life, marked 
limitation in activity, repeated heart failure hospitalizations, and increased mortality.  
Chronic severe MR is often associated with heart failure and can lead to death if left 
untreated. 
 
While mitral valve repair or replacement surgery is currently regarded as standard of care, 
many patients with clinically significant MR are at an unacceptable risk of morbidity and 
mortality and are therefore not appropriate surgical candidates.  To optimize afterload 
reduction and treatment of fluid load, these patients are often treated with medical 
management (i.e., beta blockers, ACE inhibitors, angiotensin II receptor blockers) which 
may relieve MR symptoms, but does not address the underlying cause of the condition.  
As a result, a significant portion of patients treated medically continue to progress to heart 
failure and experience an increasingly debilitating quality of life.  A significant unmet clinical 
need thus exists for the treatment of moderate-to-severe and severe MR in high surgical 
risk patients. 
 
The MitraClip® System is the first commercially available catheter-based option for the 
treatment of MR.  The MitraClip System was developed as an alternate percutaneous 
technology which may serve as a viable therapeutic option for open-heart surgery.  
Treatment with the MitraClip device allows patients to undergo a less invasive procedure 
that can mechanistically reduce MR and allow for improved quality of life.  The MitraClip 
procedure is performed under general anesthesia without the use of a heart-lung machine, 
with recovery typically lasting two to three days. 
 
The MitraClip System has been in clinical use for treatment of significant MR since 2003.  
The MitraClip System received CE (Conformité Européenne) Mark for both DMR and FMR 
indications in March 2008 and was approved by FDA for DMR indication in October 2013 
and for FMR indication in March 2019.  The system is approved for use in more than 102 
countries or regions worldwide.  More than 100,000 patients have undergone the MitraClip 
procedure worldwide.  
 
On June 15, 2020, the MitraClip System has been approved (Registration Number: 
202023130325) for clinical use in China.  
 
The MitraClip China PMS will be conducted in accordance with this Clinical Investigational 
Plan (CIP, protocol). All investigators involved in the conduct of the study will be qualified 
by education, training, or experience to perform their tasks and this training will 
documented appropriately. 
 
 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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Background and Rationale 
1.1.1 
Background 
This section summarizes results of studies in North America and Europe comprising the 
majority of the MitraClip Clinical Program as well as China and Asia-Pacific experiences. 
Rationale for the MitraClip China PMS Study is subsequently presented in the context of 
this scientific body of evidence. 
 
EVEREST I Design and Results 
The EVEREST I Feasibility trial was the first prospective, multi-center, non-randomized 
trial to evaluate the preliminary safety and effectiveness of the percutaneous MitraClip 
System in patients with moderate-to-severe (3+) or severe (4+) MR in surgical candidates. 
After undergoing the MitraClip procedure, patients were followed at discharge, 30 days, 6, 
12, 18 and 24 months and every year thereafter through 5 years. An independent 
Echocardiography Core Laboratory (ECL) assessed MR severity and other 
echocardiographic parameters at baseline and follow-up. The last patient has completed 
5-year follow-up and the study is now closed. 
 
A total of 55 patients were enrolled in the trial. The MitraClip device was implanted in 89% 
of patients and the trial met its pre-specified safety acceptance criterion, demonstrating 
mechanistic feasibility of implant and safety of the MitraClip System and procedure. There 
were no intra-procedural deaths. The procedure time averaged approximately 4 hours, 
patients were hemodynamically stable during the procedure, and the average length of 
hospital stay was approximately 3 days. A majority of patients (70.9%) experienced 
reduction in MR severity to 2+ or less at discharge. No MitraClip device embolization 
occurred in this cohort.  The rate of single leaflet device attachment (SLDA) in this initial 
cohort of patients treated was 10.2%.  A majority of SLDAs were detected early (within 30 
days post-MitraClip procedure). Patients demonstrated improvement in NYHA Functional 
Class and left ventricular measurements that were sustained through 5 years. At 5 years, 
freedom from death was 86.4% and freedom from mitral valve surgery was 55.1%. The 
results of the EVEREST I trial at 5 years provide evidence of the safety and long-term 
durability of the MitraClip device in the early cohort of patients treated in the United States. 
 
EVEREST II Randomized Controlled Trial (RCT) Design and Results 
The EVEREST II RCT is a prospective, multi-center, randomized controlled trial in which 
patients with moderate-to-severe (3+) or severe (4+) MR were randomized in a 2:1 ratio 
between the Device group (MitraClip device) and the Control group (mitral valve surgery). 
Patient follow-up occurred at discharge, 30 days, 6, 12, 18 and 24 months and yearly 
thereafter through 5 years. An independent Echocardiography Core Laboratory (ECL) 
assessed MR severity and other echocardiographic parameters at baseline and follow-up. 
The trial was intended to demonstrate superiority of safety balanced against reduced 
effectiveness of the MitraClip device when compared to mitral valve surgery. All patients 
have completed 5 years of follow-up and the study is now closed. 
 
The trial enrolled 279 patients: 184 in the Device group and 95 in the Control group. Of 
these, 178 patients in the Device group underwent the MitraClip procedure and 80 patients 

 
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in the Control group underwent mitral valve surgery. The trial met both primary safety and 
effectiveness endpoints. There were no intra-procedural deaths.  Among patients who 
underwent the MitraClip procedure in the Device group (MitraClip patients), a device was 
implanted in 89% of patients. The procedure time averaged approximately 3 hours, 
patients were hemodynamically stable during the procedure, and the average length of 
hospital stay was less than 3 days. In comparison, the average length of hospital stay for 
patients undergoing surgery in the Control group (surgery patients) was 7.5 days. A large 
majority (94.9%) of MitraClip patients were discharged home without home healthcare. In 
comparison, 71.3% of surgery patients were discharged home without home healthcare. 
A majority of MitraClip device patients (77%) experienced reduction in MR severity to 2+ 
or less at discharge, while 100% of patients undergoing mitral valve surgery in the Control 
group experienced reduction in MR severity to 2+ or less. 
 
Patients who underwent the MitraClip procedure experienced a 30-day major adverse 
event rate (composite of death, myocardial infarction (MI), re-operation for failed surgical 
repair or replacement, non-elective cardiovascular surgery for adverse events, stroke, 
renal failure, deep wound infection, ventilation for greater than 48 hours, GI complication 
requiring surgery, new onset of permanent atrial fibrillation, septicemia and major bleeding 
complication) of 7.9% versus 50% in patients who underwent mitral valve surgery in the 
Control group. Excluding the most common event of major bleeding complication, 
MitraClip device patients still experienced a lower major adverse event rate (4.5%) than 
surgery patients (11.3%) (p=0.057). 
 
Through 30 days, MitraClip patients experienced a lower site-reported adverse event rate 
than surgery patients in the following categories: cardiac rhythm disorders (atrial 
arrhythmias, bradyarrhythmia, and ventricular arrhythmias), congestive heart failure, 
peripheral edema, anemia, infections, neurologic events and respiratory events.  At 30 
days, MitraClip patients experienced a higher event rate than surgery patients in the 
following categories: atrial septal defect, myocardial ischemia, residual or recurrent MR, 
single leaflet device attachment (SLDA), gastrointestinal bleed, and vascular 
complications such as hematoma, bleed or bruising.  
 
Beyond 30 days through 5 years, site-reported adverse events occurred at a low rate in 
both MitraClip and surgery patients and there was no signal for an elevated adverse event 
rate in either group. 
 
Through 5 years, there was only one confirmed case of mitral stenosis (0.6%) reported in 
patients implanted with the MitraClip device. Through 5 years, no MitraClip device 
embolization has occurred.  SLDAs occurred at a lower rate (6.3%) than that observed in 
the EVEREST I trial (10.2%).  A majority of the SLDAs were detected early (within 30 days 
post-MitraClip procedure).   
 
There was no difference in mortality rates between patients treated in either group during 
the entire 5-year follow-up period. Freedom from mortality at 12 months, 24 months, 3 
years, 4 years and 5 years was 93.7%, 90.0%, 87.5%, 83.4% and 81.2% respectively in 
MitraClip patients, and 92.3%, 89.6%, 85.3%, 82.3%, and 79.0%, respectively in surgery 
patients. 
 

 
ABT-CIP-10263 Ver. D 
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Therefore at 5 years, the MitraClip device continues to demonstrate a favorable safety 
profile and does not present any long-term safety concerns. 
 
Freedom from mitral valve surgery in MitraClip patients at 12 months, 24 months, 3 years, 
4 years, and 5 years was 78.9%, 78.2%, 77.6%, 76.0%, and 74.3%, respectively, and 
freedom from re-operation in surgery patients was 97.4%, 96.0%, 94.4%, 94.4%, and 
92.5%, respectively. Weibull estimates of freedom from death, mitral valve surgery and 
MR > 2+ at 12 months, 24 months, 3 years, and 4 years was 60.8%, 55.4%, 52.0%, and 
49.5%, respectively, in MitraClip patients; and freedom from death, re-operation and MR 
>2+ was 89.0%, 82.6%, 77.6%, and 73.3%, respectively, in surgery patients.  While there 
was an initial drop in freedom from death, mitral valve surgery and MR > 2+ due to 
MitraClip patients undergoing mitral valve surgery within 12 months of the MitraClip 
procedure, these patients did not experience any worse deterioration in durability than 
surgery patients beyond 12 months. 
 
Significant and meaningful clinical benefits were observed in both MitraClip and surgery 
patients, which were sustained through 5 years: 
 
• MR reduction to 2+ or less at 5 years was in 82.1% of MitraClip patients and 97.6% 
of surgery patients 
• Reduction in left ventricular end diastolic volume and dimension was observed in 
both MitraClip and surgery patients, which was sustained through 5 years 
• Improvement in NYHA Functional Class was demonstrated in both groups, with 
91.5% of MitraClip patients and 97.6% of surgery patients free from NYHA 
Functional Class III or IV symptoms at 5 years 
 
The results of the EVEREST II RCT demonstrate the continued safety, durability of 
effectiveness and clinical benefit of the MitraClip device through 5 years. These results 
are consistent with the expectation of superior safety and reduced effectiveness of the 
MitraClip device when compared to mitral valve surgery. These results support an overall 
favorable risk to benefit profile of the MitraClip device through 5 years. 
 
EVEREST II High Risk Registry Design and Results 
The EVEREST II High Risk Registry is a single-arm prospective, multi-center clinical trial 
enrolling high surgical risk patients with moderate-to-severe (3+) or severe (4+) MR. 
Patients were considered high surgical risk if either their Society of Thoracic Surgery (STS) 
predicted operative mortality risk was ≥ 12%, or the surgeon investigator determined the 
patient to be high risk due to the presence of pre-specified risk factors. After undergoing 
the MitraClip procedure, patients were followed at discharge, 30 days, 6, 12, 18 and 24 
months and yearly thereafter through 5 years. All patients have completed the required 5 
years of follow-up and the study is now closed. An independent Echocardiography Core 
Laboratory (ECL) assessed MR severity and other echocardiographic parameters at 
baseline and follow-up. 
 
A total of 78 patients were enrolled in the EVEREST II High Risk Registry. The device was 
implanted in 96.2% of patients. There were no intra-procedural deaths. The procedure 

 
ABT-CIP-10263 Ver. D 
Study Name: CRD956-PMS MitraClip China 
PMS 
 
 
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time averaged approximately 3 hours, patients were hemodynamically stable during the 
procedure, and the average length of hospital stay was less than 4 days. A majority 
(75.6%) of these high surgical risk patients were discharged home without home 
healthcare. A majority of patients (71.8%) experienced reduction in MR severity to 2+ or 
less at discharge post-MitraClip procedure. 
 
The 30-day operative mortality for mitral valve replacement (using STS version 2.52) was 
7.7%, which was statistically significantly lower than the predicted surgical mortality. The 
trial thus met the pre-specified primary safety endpoint. This rate was comparable to the 
observed mortality at 30 days in the Concurrent Control (8.3%). Major adverse events at 
30 days occurred at a rate (26.9%) consistent with their co-morbidities, with transfusions 
≥ 2 units of blood contributing the majority of events. At 12 months, freedom from death in 
the High Risk Registry patients was higher (75.4%) than that observed in the Concurrent 
Control (55.3%). SLDAs occurred at a low rate (1.3%). 
 
MR reduction to 2+ or less in this high surgical risk population was sustained in 75.0% of 
patients through 5 years. For this high surgical risk population with limited options to treat 
MR, safe reduction of MR is clinically meaningful, as observed in the following endpoints: 
 
• 45% reduction in the 12-month rate of hospitalization for heart failure post-treatment 
compare with the 12-month rate prior to MitraClip intervention 
• Reduction in left ventricular end diastolic volume and dimension, and left ventricular 
end systolic volume, which was sustained through 5 years 
• NYHA Functional Class was improved from approximately 90% of patients in NYHA 
Functional Class III or IV at baseline to 83.7% free from NYHA Functional Class III 
or IV symptoms at 5 years 
 
The results of the EVEREST II High Risk Registry demonstrate continued safety, durability 
of effectiveness and clinical benefit of the MitraClip device through 5 years. These results 
support an overall favorable risk to benefit profile of the MitraClip device in high surgical 
risk patients through 5 years. 
 
EVEREST II REALISM Study Design and Results 
The objective of the EVEREST II REALISM Continued Access Registry was to collect data 
on the use of the minimally-invasive catheter-based MitraClip device under “real-world” 
conditions in high risk and non-high risk patients with moderate-to-severe (3+) or severe 
(4+) chronic MR. REALISM was a prospective, multi-center, Continued Access Registry. 
The study enrolled patients in two arms: the high risk and non-high risk arms. Eligibility for 
the Non-High Risk arm was the same as for the EVEREST II RCT and that for the High 
Risk arm was the same as for the HRR. 
 
Enrollment in the Continued Access REALISM study was initiated on January 22, 2009. A 
total of 899 patients (628 High Risk, 271 Non-High Risk) were enrolled and treated in the 
EVEREST II REALISM Continued Access Study.  Enrollment in the Non-High Risk arm of 

 
ABT-CIP-10263 Ver. D 
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the study concluded on April 14, 2011 and enrollment in the High Risk arm concluded on 
December 19, 2013. 
 
All-cause mortality and major adverse event rates at 30 days in the REALISM High Risk 
arms were 4.1% and 15.6% respectively. The 12 months all-cause mortality and major 
adverse event rates were 23.4% and 35.5% respectively. 
 
The severity of MR consistently remained mild to moderate (2+ or less) for a majority 
(>80%) of the patients and the NYHA Functional Class were Class I/II for a majority (>80%) 
of the patients through 5 years.  
 
The safety and durability results of the REALISM High Risk arms provide further evidence 
that the “real-world” use of the MitraClip device continues to perform as expected based 
on the EVEREST II Randomized Controlled Trial and High Risk Registry.    
 
MitraClip Experiences in Chinese and Asian-Pacific Population 
Early experience of the MitraClip device in China has been reported.1  Of the 3 cases 
reported, two patients had FMR and one patient had DMR.  In all 3 cases, the MitraClip 
device was successful implanted.  In the first two cases, follow up was completed through 
6-month with no adverse events reported. Discharge echocardiography showed significant 
reduction in MR, decreases in left atrial and left ventricular inner diameters, decreases in 
systolic pulmonary artery pressure, and NYHA class improvement when compared to 
baseline.  These results were maintained through 6 months.  In the third patient, MR was 
significantly reduced from discharge to 1 month.  After month two, however, the patient’s 
MR increased, left atrium and ventricle were further enlarged, cardiac function further 
deteriorated, even though multiple echocardiography results showed that the MitraClip 
device was still attached well.  After treatment with aggressive heart failure medications, 
the patient died 162 days post implant due to heart failure and cardiogenic shock.    
Additionally, Liu et al reported a single center experience with the MitraClip device.2  A 
total of 10 patients were treated with the MitraClip device, including eight patients treated 
with FMR and two patients treated with DMR.  The mean age was 74 years.  The 
procedure success was 100%.  Five patients were implanted with one MitraClip device 
and the remaining 5 patients had 2 MitraClip devices implanted.  Acute MR reduction by 
3 grades was achieved in 5 patients and by 2 grades in the other 5 patients. Thirty-day 
follow-up results demonstrated significant improvements from baseline in MR grade (3.9 
vs. 1.7), LVEF (40.2% vs. 44.8%), quality of life measures (0.7 vs. 0.9), 6-minute walk test 
(279 vs. 344 m), NYHA class (2.9 vs. 2.1), left atrium end diastolic dimension (6.4 vs. 6.0 
cm), and left ventricle end diastolic dimension (6.1 vs. 6.0 cm).  There was no mitral valve 
surgery due to MitraClip failure, myocardial infarction, death, MitraClip detachment, 
thromboembolization, MV damage, mitral stenosis, tamponade, stroke or newly occurred 
atrial fibrillation observed in the study. The study concluded that the initial experience with 
intravascular mitral valve repair using the MitraClip system demonstrated that the 
procedure was safe and effective, resulting in substantial echocardiographic and early 
clinical improvement. The long-term benefit of MitraClip should be validated through 
follow-up.  

 
ABT-CIP-10263 Ver. D 
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Most recently, Lee et al. published their results of MitraClip performance in Chinese 
population.3 They enrolled a total of 20 patients with heart failure and severe MR, including 
DMR (55%), FMR (40%) and mixed (5%). The mean age of the cohort was 75 years. 
Among the 20 procedures, 4 were performed emergently while the patients were on 
mechanical hemodynamic support or inotropic agents. On average, 1.8 clips were 
implanted in this cohort and the acute procedure success was 95%. There was no peri-
procedure death, MI, stroke or any adverse events requiring emergent cardiac surgery. 
One patient died within 30 days post procedure due to deteriorating hyperbilirubinemia 
when MR was not successfully abolished. The 30-day mortality was 5%. Thirty-day follow-
up results showed MR was significantly reduced (1+: 70%, 2+: 20%, 3+: 5%) compared to 
baseline (4+: 100%). Patient’s functional status was also significantly improved. All 
patients were with NYHA class I or II at 30 days post procedure; the six-minute walk 
distance increased from 219.6 to 279.1 meters (p = 0.04). The study concluded that trans-
catheter edge-to-edge mitral valve repairs are safe and effective in Asians with 
symptomatic MR, regarding the improvements of clinical symptoms and exercise 
capacities. 
In addition, a MitraClip Asia-Pacific Registry (MARS) was conducted by eight study sites 
in five Asia-Pacific countries, including Zhejiang University School of Medicine, Hanzhou, 
China. 4  The objective of the registry was to describe and compare the used of the 
MitraClip therapy in DMR and FMR. As reported, acute procedure success rates for FMR 
and DMR were similar (95.5% vs. 92%, p=0.515).  The 30-day mortality and MAE rates 
were 4.5% vs. 6.7% (p=0.555) and 9.2% vs. 14.7% (p=0.281) for FMR and DMR 
respectively. In both FMR and DMR patients, there was marked improvement of the 
severity of MR 30-day post-procedure.  The percent of patient with NYHA class I-II was 
increased from 21.6% vs. 38.7% to 78.9% vs. 78.2% at 30-day post implant for FMR and 
DMR respectively.  Hemodynamically, the mean mitral valve pressure gradient was 3.7 
vs. 4.0 mmHg and MR ≥ 2+ was reduced to 10.7% vs. 14.3% at 30-day follow-up for FMR 
and DMR respectively.  For FMR, there was a significant reduction in LVEDD, LA indexed 
volume and PASP at 30 days.  For DMR, LVEDD and LVESD were significantly reduced.  
In this study, it was concluded that the MitraClip device is a safe and effective option for 
patients with both FMR and DMR. 
 
1.1.2 
Rationale for Conducting this Post Market Study 
The safety and efficacy of MitraClip have been demonstrated in these patients in U.S. 
clinical studies such as EVEREST II HRR trial and EVEREST II REALISM HRR trial, 
described above.  The data also showed the safety and efficacy of MitraClip in Chinese 
and other Asia-Pacific patients. Per National Medical Products Administration (NMPA) 
post approval request, the MitraClip China PMS is planned to confirm the evidence of 
safety and efficacy of MitraClip System in Chinese subjects with symptomatic MR. Upon 
completion of the study, a study report will be submitted to fulfill NMPA post approval 
requirement.  
 

 
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2 
STUDY OVERVIEW 
 Study Objective 
To confirm the evidence of safety and efficacy of MitraClip System in Chinese symptomatic 
MR subjects with a post market setting. 
 
 
Device used in the Study 
2.2.1 
Name of the Device 
Device to be used in the MitraClip China PMS is the MitraClip system (CDS0601-NTR, 
CDS0601-XTR, SGC0301).  
 
2.2.2 
Indication for Use 
MitraClip procedures for this study will be conducted in accordance with the Instructions 
for Use (IFU) approved by NMPA. 
 
2.2.3 
Description of the Device 
The MitraClip System consists of two parts: 1) the Clip Delivery System and 2) the 
Steerable Guide Catheter.   
 
The MitraClip Device grasps and coapts the mitral valve leaflets resulting in fixed 
approximation of the mitral leaflets throughout the cardiac cycle.  The MitraClip Device is 
placed without the need for arresting the heart or cardiopulmonary bypass.  Please refer 
to the IFU of MitraClip System for detailed information regarding the device used in this 
study. 
 
Components of the MitraClip System are described as follows: 
 
1) The Clip Delivery System (CDS) (sterilized and disposable) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Steerable Sleeve 
Clip 
Delivery Catheter 
Steerable Sleeve 
Clip 
Delivery Catheter 

 
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The CDS consists of three major components: 1) the MitraClip Implant (Clip), 2) the 
Steerable Sleeve, and 3) the Delivery Catheter. The CDS is introduced into the body 
through an SGC and is used to advance and manipulate the Clip for proper positioning 
and placement on the mitral valve leaflets. The CDS is designed to deploy the implant in 
a way that requires multiple steps to ensure safe delivery of the device.   
 
The Clip is shown as follows: The Clip is manufactured with metal alloys and polyester 
fabric (Clip cover) that are commonly used in cardiovascular implants.  The Clip arms can 
be adjusted to any position from fully opened, fully inverted to fully closed.  These positions 
are designed to allow the Clip to grasp and approximate the leaflets of the mitral valve 
using controls on the Delivery Catheter Handle.  The Clip can be locked, unlocked and 
repeatedly opened and closed.  The Grippers can be raised or lowered repeatedly.  
 
 
 Clip cover   Gripper 
 
2) The Steerable Guide Catheter (SGC) (sterilized and disposable) 
 
 
Silicone Pad 
Steerable Guide Catheter 
Dilator 

 
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Fastener 
 
The SGC includes a Steerable Guide Catheter, a Dilator, a Silicone Pad, and a Fastener. 
The Steerable Guide Catheter and the Dilator are used to introduce the CDS into the left 
side of the heart through the interatrial septum.  The SGC is also used to position and 
orient the Clip to the appropriate location above the mitral valve.  The Dilator is used for 
the introduction of the SGC into the femoral vein and left atrium.   
 
3) Other accessories 
Several Class I accessories are used in conjunction with the MitraClip System including: 
1) a Stabilizer, 2) a Lift and 3) a Support Plate to support and position the System during 
the procedure. All above 3 accessories have been filed at NMPA as Class I medical 
device.  
 
 
1) Stabilizer (unsterilized and reusable. Please refer the IFU regarding sterilization.) 
 
 
 
 
 
 
 

 
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2) Lift (unnecessary to sterilize and reusable) 
 
 
 
 
3)  Support Plate (unnecessary to sterilize and reusable) 
 
 
 
3 
STUDY DESIGN 
The MitraClip China PMS is a prospective, multi-center, single-arm, post market study 
designed to collect data on use of the MitraClip System in Chinese subjects. A minimum 
of 50 subjects and a maximum of approximately 100 will be registered up to 10 sites in the 
MitraClip China PMS.  Follow-up of subjects registered in the MitraClip China PMS will 
occur at discharge, 30 days and 1 year. The total duration of the study is expected to be 
approximately 30 months. 
 
 
Study Procedure and Follow-up Schedule 
Figure 1 shows an overall flow of the study. Subjects will be screened for study eligibility 
by the Investigator as well as the local Site Heart Team per the inclusion and exclusion 
criteria.  A cardiac surgeon and an echo specialist assess subjects for eligibility criteria for 
surgical risks and echocardiography, respectively.  
 
 

 
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Figure 1:  Study Flow Chart 
 
 Measures Taken to Avoid and Minimize Bias 
The following steps will be taken to minimize bias:   
 
• 
Study sites will attempt to recruit consecutive subjects who meet the study eligibility 
criteria 
• 
Baseline and follow-up echocardiographic parameters will be confirmed by an 
independent Echocardiography Core Laboratory  
• 
Standardized scripts will be implemented at study sites for the assessment of NYHA 
classification, and Kansas City Cardiomyopathy Questionnaire (KCCQ) 
 
 
Early Termination of the Study 
While no formal statistical rule for early termination of the study is defined, the Sponsor 
reserves the right to discontinue the study at any stage or reduce the follow-up period with 
suitable written notice to the investigator.  
 
Should the Sponsor discontinue the study, sites will follow subjects per routine hospital 
practice with device-related AEs reported to the Sponsor as per vigilance/commercial 
reporting requirements. The investigator shall provide a written statement to the EC (if 
applicable). All applicable study documents shall be subject to the same retention policy as 
detailed in Section 11.5 of the protocol.  
Subject meets general eligibility 
criteria 
MitraClip Index Procedure 
Patient signs ICF 
Echocardiography confirms MR severity, MVA size 
and no evidence of thrombus 
Follow-up at discharge, 30 days 
and 12 months 

 
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If the Sponsor suspends or prematurely terminates the clinical study at an individual site in 
the interest of safety, the Sponsor will inform all other Principal Investigators and ECs. 
 
If suspension or premature termination occurs, the Principal Investigator or authorized 
designee will promptly inform the registered subjects at his/her site, if appropriate, and 
return patients to their standard medical treatment. 
 
A Principal Investigator, EC, or regulatory authority may also suspend or prematurely 
terminate participation in the clinical study at the site(s) for which they are responsible. The 
investigators will follow the requirements specified in the Clinical Trial Agreement.  
 
If a suspended study is to be resumed, a prior approval should be obtained from the EC 
and a notification should be sent to the regulatory bodies. 
 
4 
ENDPOINTS 
 
Primary Endpoints  
Two primary endpoints are designed for the MitraClip China PMS. 
• Acute procedural success (APS).  APS is defined as successful implantation of the 
MitraClip device(s) with resulting MR severity of 2+ or less as determined by the 
ECL assessment of a discharge echocardiogram (30-day echocardiogram will be 
used if discharge echocardiogram is unavailable or uninterpretable).  Patients who 
die or who undergo mitral valve surgery before discharge are an APS failure. 
• Freedom from major adverse event (MAE) at 30 days. MAE is a composite of death, 
stroke, MI, renal failure, and non-elective cardiovascular surgery for device or 
procedure related adverse events occurring after the femoral vein puncture for 
transseptal access. 
 
 
Descriptive Endpoints 
Clinical Endpoints 
The following descriptive clinical endpoints will be assessed at all scheduled office visits. 
• All-cause mortality  
• Freedom from the components of MAE  
• NYHA Functional Class  
• Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life (QoL) scores   
• Six Minute Walk Test (6MWT) distance  
• Mitral valve surgery (including type of surgery), including reason for intervention 

 
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• Additional MitraClip System intervention, including reason for intervention 
• Number of hospitalizations and reason for hospitalization (i.e. heart failure, 
cardiovascular, non-cardiovascular)  
• Device-related complications: defined as a composite of single leaflet device 
attachment (SLDA), device embolization, clinically significant iatrogenic septal 
defect or mitral stenosis that requires intervention. 
• Major bleeding  
 
Device and Procedure-Related Endpoints 
• Total Procedure Time: defined as the time elapsed from the first of any of the 
following: intravascular catheter placement, anesthesia or sedation, or 
transesophageal echocardiogram (TEE), to the removal of the last catheter and 
TEE 
• Device Procedure Time: Defined as the time elapsed from the start of the 
transseptal procedure to the time the Steerable Guide Catheter is removed 
• Device Time: Defined as the time the Steerable Guide Catheter is placed in the 
intra-atrial septum until the time the MitraClip Delivery System is retracted into the 
Steerable Guide Catheter 
• Fluoroscopy Time: defined as the total minutes of exposure to fluoroscopy during 
the MitraClip procedure 
• Length of stay in Intensive Care Unit/Critical Care Unit/Post-Anesthesia Care Unit 
(ICU/CCU/PACU) 
• Length of hospital stay for index MitraClip procedure  
 
Echocardiographic Endpoints 
The following descriptive echocardiographic endpoints will be assessed at all scheduled 
office visits. 
• MR Severity Grade 
• Effective Regurgitant Orifice Area 
• Regurgitant Volume (RV) 
• Regurgitant Fraction (RF) 
• Left Ventricular End Diastolic Volume (LVEDV) 
• Left Ventricular End Systolic Volume (LVESV) 
• Left Ventricular End Diastolic Dimension (LVEDD) 
• Left Ventricular End Systolic Dimension (LVESD) 
• Left Ventricular Ejection Fraction (LVEF) 

 
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• Right Ventricular Systolic Pressure (RVSP) 
• Mitral Valve Area (MVA) 
• Mean Mitral Valve Pressure Gradient (MVG) 
• Systolic Anterior Motion of the mitral valve (present or absent) 
• Forward Stroke Volume (FSV) 
• Cardiac Output (CO) 
• Cardiac Index (CI) 
 
5 
SUBJECT SELECTION AND WITHDRAWAL 
 
Subject Population 
The MitraClip China PMS will enroll and registered male and female Chinese subjects with 
symptomatic MR who satisfy the inclusion and exclusion criteria and who are treated with 
the MitraClip System.  Subjects must provide written informed consent to participate the 
study prior to conducting MitraClip procedure. 
 
 
Subject Recruitment/Screening and Informed Consent 
5.2.1 
Subject Recruitment and Screening 
The Principal Investigator at the site has the overall responsibility for recruitment and 
screening subjects for the MitraClip China PMS.  Subjects must be screened for general 
eligibility by a delegated member of the site’s study team previously trained to the PMS 
protocol.  
 
A patient who does not satisfy all general eligibility criteria prior to informed consent is 
considered a recruitment failure and should not be enrolled in the study. 
 
Potential subjects presenting at the clinical sites who meet general inclusion criteria and 
no general exclusion criteria will be fully informed about the MitraClip China PMS, following 
the established Informed Consent process described in section below.  Once a duly dated 
and signed Informed Consent form (ICF) is obtained, the study-specific screening 
procedure may begin.  
 
Subjects who do not meet the study screening criteria are considered a screen failure and 
should be withdrawn from the study. The Principal Investigator or the delegated study 
personnel will record the screen failure in the hospital records and on a 
recruitment/screening log as required. 
 
All subjects who are found to meet all inclusion and no exclusion criteria must have a 
documented in-person consultation with the Cardiothoracic (CT) Surgeon investigator to 
assess surgical risk.  The MitraClip implanter (who may also be the Principal Investigator) 

 
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and a physician trained in echocardiography will also assess anatomic suitability of the 
subject for eligibility in the study.   
 
The responsibilities of the various roles/specialties on the local site heart team are 
summarized below: 
 
Role / Specialty 
Responsibility 
Interventional 
Cardiologist 
1. Local Site Heart Team Member 
2. Screens potential subjects  
3. Performs MitraClip procedure* 
CT Surgeon 
1. Local Site Heart Team Member 
2. Provides in-person assessment of surgical difficulty 
Echocardiographer 
1. Local Site Heart Team Member 
2. Evaluates potential subjects for echocardiographic eligibility criteria 
3. Participates in the MitraClip procedure 
* The MitraClip Implanter can be Interventional Cardiologist, CT Surgeon, or Echocardiographer provided that he/she 
has completed the mandatory MitraClip Therapy Training and is authorized by the Sponsor and the Principal 
Investigator to perform the MitraClip procedure 
 
5.2.2 
Informed Consent 
The Investigator or his/her authorized designee (if applicable) will conduct the Informed 
Consent process, as required by applicable regulations and the center’s EC. This 
process will include a verbal discussion with the patient on all aspects of the study that 
are relevant to the patient’s decision to participate, such as details of study procedures, 
anticipated benefits, and potential risks of study participation. Sites must inform patients 
about their right to withdraw from the study at any time and for any reason without 
sanction, penalty, or loss of benefits to which the patient is otherwise entitled. Withdrawal 
from the study will not jeopardize their future medical care or relationship with the 
investigator.  
 
During the discussion, the Principal Investigator or his/her authorized designee will avoid 
any improper influence on the patient and will respect patient’s legal rights. Financial 
incentives will not be given to patients. Patients may be compensated for time and travel 
directly related to the participation in the study. The site shall provide the patient with the 
Informed Consent form written in a language that is understandable to the patient and 
that has been approved by the center’s EC. The patient shall have adequate time to 
review, ask questions, and consider participation. The Principal Investigator or his/her 
authorized designee will make efforts to ensure that the patient understands the 
information provided. If the patient agrees to participate, they must sign and date the 
Informed Consent form, along with the person obtaining the consent prior to any study-
specific procedures. The site will file the signed original in the patient’s hospital or 
research charts, and provide a copy to the patient. 
 
Sites should report any failure to obtain informed consent from a patient to the Sponsor 
within 5 working days and to the reviewing site’s EC according to the EC’s reporting 
requirements. 
 

 
ABT-CIP-10263 Ver. D 
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If, during the study, new information becomes available that can significantly affect a 
subject's future health and medical care, the Principal Investigator or his/her authorized 
designee (if applicable) will provide this information to the subject. If relevant, sites will 
ask the subject to confirm their continuing informed consent in writing. 
 
5.2.3 
Special Circumstances for Informed Consent 
This study excludes individuals unable to make the decision to participate in a clinical study 
on their own or who are unable to fully understand all aspects of the study that are relevant 
to the decision to participate, or who could be manipulated or unduly influenced as a result 
of a compromised position, expectation of benefits or fear of retaliatory response. 
 
This study excludes individuals who require emergency use of the device or concomitant 
interventional procedures, e.g. left atrial appendage closure (LAAC), undertaking during 
the same procedure. 
 
 
Eligibility Criteria 
5.3.1 
Eligibility Assessment 
Assessment for general eligibility criteria is based on medical records of the site and 
interview with a candidate patient. Patients must meet ALL general inclusion criteria to 
participate in the study. If ANY general exclusion criteria are met, the patient is excluded 
from the study and cannot be enrolled (recruitment failure). 
 
If any clinical and/or laboratory tests are required for patient screening and are not included 
in a site’s standard tests, they must be completed after written informed consent is 
obtained.  
 
5.3.2 
Inclusion Criteria 
Subjects must meet ALL of the following inclusion criteria: 
 
1. Subjects is eligible to receive the MitraClip per the current approved MitraClip 
System IFU. (If any update or amendment on the IFU, the latest version of IFU 
shall be followed.)  
2. Subject is 18 years-old or above. 
3. Subjects who give consent for study procedure. 
 
5.3.3 
Exclusion Criteria 
Subjects must NOT MEET ANY of the following exclusion criteria: 
 

 
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1. Subject cannot tolerate procedural anticoagulation or anti-platelet regimen. 
2. Subject with active endocarditis of mitral valve. 
3. Subject with rheumatic mitral valve disease. 
4. Subject with echocardiographic evidence of intracardiac, IVC or femoral venous 
thrombus.  
5. Subject is unlikely to survive the protocol follow up period of 12-months after 
device implant. 
6. Subject has insufficient or lost ability to maintain their will and rights. 
7. Subject is illiterate. 
8. Pregnant or nursing subjects and those who plan pregnancy during the study 
follow-up period  
9. Subject participates in another clinical study that may impact the follow-up or 
results of this study. 
 
 
Subject Enrollment and Registration 
The subject is considered to be enrolled in the study upon signing and dating the informed 
consent form. Subjects will be considered registered upon femoral vein puncture for 
transseptal access in preparation for MitraClip System insertion.  
 
 
Subject Withdrawal and Discontinuation 
Each registered subject shall remain in the study until completion of the required follow-
up period; however, a subject’s participation in any clinical study is voluntary and the 
subject has the right to withdraw at any time without penalty or loss of benefit.  If the subject 
decides to withdraw prior to the 1-year follow-up visit, all available data prior to formal 
documentation of withdrawal from the study must be collected.  Conceivable reasons for 
discontinuation may include, but not be limited to, the following:  
 
• 
Subject death 
• 
Subject voluntary withdrawal  
• 
Investigator judgment of subject discontinuation 
• 
Subject lost-to-follow-up as described below 
 
Sites must notify the Sponsor of the reason(s) for subject discontinuation. Investigators 
must also report this to their respective EC as defined by their institution’s procedure(s).  
 
No additional follow-up is required or data recorded from subjects once withdrawn from 
the study, except for the status (deceased/alive). 
 

 
ABT-CIP-10263 Ver. D 
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However, if a subject withdraws from the study due to problems related to the safety or 
performance of the device under study, the investigator shall ask for the subject's 
permission to follow his/her status/condition outside of the study.   
 
In case of subject voluntary withdrawal, the site should make attempts to schedule the 
subject for a final study visit.  
 
Lost-to-Follow-up: 
If the subject misses two consecutive scheduled follow-up time points and the attempts at 
contacting the subject detailed below are unsuccessful, then the subject is considered lost-
to-follow-up. Site personnel shall make all reasonable efforts to locate and communicate 
with the subject (and document these efforts in the source documents), including the 
following, at each contact time point: 
 
• A minimum of two telephone calls on different days over the specified follow-up 
windows to contact the subject should be recorded in the source documentation, 
including date, time and initials of site personnel trying to make contact. 
• If these attempts are unsuccessful, the site should send a letter (certified if 
applicable) to the subject. 
• If a subject misses one or more non-consecutive follow-up contact time points, it 
will be considered a missed visit. The subject may then return for subsequent visits. 
If the subject misses two consecutive time points and the above-mentioned 
attempts at communicating with the subject are unsuccessful, the subject will be 
considered lost-to-follow-up.  
 
Note: Telephone contact with General Practitioner, non-study cardiologist or relative 
without the presence of the subject or indirect documentation obtained via discharge 
letters will not be considered as subject contact. 
 
 
Number of Subjects 
The study will register a minimum of 50 subjects and maximum of approximately 100 
subjects.  
 
 
Total Expected Duration of the Clinical Study 
The expected duration of registration is 18 months. The expected duration of each 
subject’s participation is 12 months, including the scheduled visits and data collection for 
this study that will occur at 30 days and 12 months visits. Subjects will exit the trial at the 
end of their 12-month follow-up visit. Therefore, the total duration of the study is expected 

 
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to last 30 months, consisting of approximately 18 months of registration plus 12 months of 
follow-up.  
 
6 
TREATMENT AND EVALUATION OF ENDPOINTS 
 
Baseline 
6.1.1 
Transthoracic & Transesophageal Echocardiograms to Confirm Subject Eligibility 
Eligibility assessments based on transthoracic echocardiogram (TTE) must be performed 
based on images obtained within 90 days prior to MitraClip procedure. Eligibility 
assessments based on transesophageal echocardiogram (TEE) must be performed based 
on images obtained within 180 days prior to procedure.     
 
The TTE and TEE images obtained by sites are submitted to the ECL for analysis.  
 
6.1.2 
Clinical Assessments 
Within 14 days prior to the MitraClip procedure, a baseline visit must be completed.  A 
complete list of clinical assessments to be completed at the baseline is listed in Table 1 
presents the Clinical Evaluation Schedule detailing assessments at each visit.  These 
clinical assessments are standard assessments for most cardiac/structural heart 
interventional procedures and therefore should be administered per standard of care at 
each Institution. 
Table 1:  Clinical Evaluation Schedule.  Clinical assessments at baseline include heart 
rate, blood pressure, Kansas City Cardiomyopathy Questionnaire (KCCQ), New York 
Heart Association (NYHA) Functional Class, Six Minute Walk Test (6MWT) distance, blood 
test, STS Mortality Risk Score (for mitral valve replacement), and EuroScore II 
assessments.  Concomitant cardiac medications will also be collected at this visit. 
 
6.1.3 
12-Lead ECG 
A 12-lead ECG must be performed within 24 hours prior to the MitraClip procedure to rule 
out an acute ischemia or myocardial infarction (Table 1 presents the Clinical Evaluation 
Schedule detailing assessments at each visit.  These clinical assessments are standard 
assessments for most cardiac/structural heart interventional procedures and therefore 
should be administered per standard of care at each Institution. 
Table 1:  Clinical Evaluation Schedule). 
 
 
Anticoagulation and Antiplatelet   
Discontinue the use of warfarin for at least three (3) days prior to the scheduled MitraClip 
procedure and ensure that the international normalized ratio (INR) ≤ 1.7.  Similarly, 
discontinue dabigatran or factor Xa inhibitors for a sufficient duration to ensure restoration 
of normal coagulation.  Subjects may be treated with heparin during this period at the 

 
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treating physician’s discretion.  If heparin is used, it must be discontinued ≥ 4 hours prior 
to the MitraClip procedure for intravenous unfractionated heparin (UFH). 
 
Administer a dose of clopidogrel or other thienopyridines, at a dosage determined by the 
Investigator, either just prior to, or immediately following the procedure.  If aspirin is to be 
used, a dose of 325 mg may be administered either just prior to, or immediately post-
MitraClip procedure. 
 
 
Subject Preparation 
Prior to the MitraClip procedure, subjects must be assessed to ensure there is no 
significant change in the subject’s overall condition (e.g., stroke, MI, active infection, 
endocarditis, hemodynamic instability, etc.) that would preclude treatment.  If the subject 
has experienced any significant change that would preclude treatment, the subject must 
be treated and reassessed for the study. Such subjects are not considered registered.  
 
Prior to the MitraClip procedure, baseline activated clotting time (ACT) must be determined 
following transseptal puncture for the MitraClip procedure.  ACT and heparin 
administration (or alternative anticoagulation therapy) must be recorded. 
 
Subjects must be prepared for the procedure as per the institution’s standard practice for 
a percutaneous procedure, general anesthesia, and TEE.   
 
 
MitraClip Procedure 
Refer to IFU including storage and handling requirements, preparation for use, pre-use 
checks of safety and performance, and precautions to be taken after use. 
 
Subjects are required to undergo an additional transesophageal (TEE) echocardiogram 
immediately preceding initiation of the MitraClip procedure to rule out the presence of 
intracardiac mass, thrombus or vegetation.  This echocardiogram will not be submitted to 
the Echocardiography Core Laboratory.   
 
If a thrombus is identified, the subject may be pharmacologically treated to resolve the 
thrombus and, if successful, the subject may be reassessed for the MitraClip China PMS 
Study.   
 
Femoral vein transseptal catheterization will be completed in accordance with the IFU.  
Subjects will be considered registered upon femoral vein puncture for transseptal access 
in preparation for the MitraClip System insertion.  Following transseptal crossing, 
administer intravenous heparin (or alternative anticoagulation therapy; e.g., bivalirudin) in 
accordance with standard hospital practice.  Maintain an ACT (activated clotting time) of 
> 250 seconds throughout the procedure.  
 
The Steerable Guide Catheter (Guide) is inserted into the femoral vein and advanced 
across the transseptal puncture.  Fluoroscopic and echocardiographic guidance will be 
used during the procedure to visualize the devices and the vasculature and cardiac 

 
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anatomy.  For subjects with renal dysfunction, intravenous contrast should not be used 
during the procedure unless absolutely necessary. 
 
The Guide is positioned over the mitral valve and the MitraClip Delivery System is inserted 
into the Guide and properly positioned over the mitral valve.  The MitraClip Delivery 
Catheter is advanced until the MitraClip device emerges from the tip of the Guide into the 
left atrium.  Manipulations of the catheter tip (via the control knobs on the handles) will 
continue in the left atrium until the MitraClip device is properly oriented perpendicular to 
the line of coaptation of the mitral valve.  The MitraClip device is opened and advanced 
across the mitral valve into the ventricle then pulled back to grasp the leaflets.  Two-
dimensional and/or 3-dimensional echocardiography and color flow Doppler are used to 
evaluate the presence of a double orifice, leaflet insertion, MitraClip device position and 
residual MR.  If the MitraClip device is not positioned properly or MR has not been 
adequately reduced, additional grasping may be attempted and the MitraClip device may 
be inverted in the left atrium as required for additional grasping attempts.  When placement 
is successful, the MitraClip device is closed and deployed from the Delivery Catheter.  The 
catheters are then removed from the subject. 
 
If MR reduction is not adequate, an additional MitraClip device may be placed at the 
implanter’s discretion, depending on patient clinical condition, mitral valve area and mean 
Mitral Valve Gradient.    
 
 
Post–MitraClip Procedure 
Immediately following the MitraClip procedure, heparin (or alternative anticoagulation 
therapy; e.g., bivalirudin) must be discontinued and the ACT should be monitored in 
accordance with hospital standard of care.  Vascular sheaths should be removed 
according to usual hospital practice. 
 
Administer additional intravenous doses of antibiotics at approximately 6 and 12 hours (or 
per institutional guidelines) after the completion of the procedure. 
 
Subjects will receive standard post-cardiac catheterization procedure care as judged 
appropriate by the Investigator.   
 
Subject weight, blood pressure, heart rate and temperature must be obtained prior to 
subject discharge from the hospital. 
 
At discharge, each subject implanted with MitraClip device must be provided an Implant 
Identification Card.  An Implant Identification Card is included in the package with each 
MitraClip System.  The subject must be instructed to keep this Implant Identification Card 
with them at all times.  The serial number of all implanted MitraClip device(s) must be 
recorded on the Implant Identification Card. 
 
The Investigator must instruct all subjects who receive the MitraClip device of the need for 
prophylaxis for endocarditis, as recommended in the guidelines for the prevention and 
treatment of infective endocarditis (JSC 2008)5.  Subjects must be instructed to notify the 

 
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Investigator or the subject’s primary care physician in the event that a procedure 
recommended by this Guideline is planned, so that prophylactic antibiotics can be 
prescribed.   
 
Post-MitraClip procedure anticoagulation is recommended per the Investigator’s discretion 
as follows: 
 
1. Reinitiate warfarin, dabigatran or factor Xa inhibitor (if discontinued for the MitraClip 
procedure) at pre-procedure levels or as appropriate.  If chronic oral anticoagulation 
is used, then aspirin and ticlopidine use are not recommended, but are allowed if 
otherwise indicated for other conditions. 
2. If chronic oral anticoagulation is not used, it is strongly recommended that either 
daily clopidogrel or other thienopyridines, at a dosage determined by the 
Investigator and/or aspirin (100 mg) is administered for 6 months or longer.  
  
 
Follow-up for All Subjects 
Clinical follow-up will be performed at the following intervals for all registered subjects:  
 
• 
Discharge post-MitraClip procedure 
• 
30 days follow-up office visit (+14 days) (this visit must be conducted even if subject 
is in hospital) 
• 
1 year follow-up office visit (365 ± 45 days)   
 
During the follow-ups, all subjects will be treated per applicable standards of care 
consistent with the subject’s condition.  Subjects implanted with the MitraClip device must 
also be evaluated for device integrity. If MitraClip was not implanted, the subject will be 
followed for 30 days for safety monitoring. 
  

 
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Table 1 presents the Clinical Evaluation Schedule detailing assessments at each visit.  These clinical assessments are standard 
assessments for most cardiac/structural heart interventional procedures and therefore should be administered per standard of care 
at each Institution. 
Table 1:  Clinical Evaluation Schedule 
Assessments 
 
Screening 
Baseline 
Hospital 
Discharge 
30 Days 
1 Year 
+14 days 
± 45 days 
Medical history 
X 
X1 
 
 
 
Evaluation by Local Site Heart Team 
X 
 
 
 
 
Weight, temperature, blood pressure and heart rate 
X 
X2 
X 
X 
X 
Concomitant cardiac medications including dose   
 
X1 
X 
X 
X 
CBC with differentials and platelet count 
 
X1 
X 
X 
X 
Serum Creatinine 
 
X1 
X 
X 
X 
Blood Urea  
 
X1 
X 
X 
X 
BNP and NT-proBNP 
 
X1 
X 
X 
X 
CK and CK-MB 
 
X1 
X 
X 
X 
Pregnancy test 
 
X1,3 
 
 
 
STS Mortality Risk Score for mitral valve replacement 
 
X1 
 
 
 
EuroScore II 
 
X1 
 
 
 
12-Lead ECG 
 
X2 
 
 
 
Transesophageal Echocardiography (TEE) 
X4 
X5 
 
 
 
Transthoracic Echocardiography (TTE) 
X6 
X7 
X 
X 
X 
NYHA Classification 
 
X1 
 
X 
X 
Six Minute Walk Test (6MWT) distance 
 
X1 
 
X 
X 
KCCQ 
 
X1 
 
X 
X 
Adverse events 
 
 
X 
X 
X 
1. 
Within 14 days prior to MitraClip procedure 
2. 
Performed within 24 hours prior to MitraClip procedure 
3. 
Female subject within the child bearing age only 
4. 
Within 180 days prior to MitraClip procedure;  
5. 
TEE immediately prior to the MitraClip procedure 
6. 
Within 90 days prior to MitraClip procedure 

 
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7. 
Screening test can be used if the screening test is within 14 days prior to MitraClip procedure 
   

 
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Additional Follow-up Visits for All Subjects 
Additional subject visits may occur as clinically warranted. The following 
information must be collected as applicable:  
 
• 
Adverse events 
• 
Concomitant cardiovascular medications including dosage 
• 
Hospitalizations 
• 
Mitral valve surgery 
• 
Additional MitraClip procedure(s)    
 
7 
ADVERSE EVENTS 
To comply with worldwide standards and guidelines on clinical study adverse event 
reporting, the Sponsor has adopted uniform and worldwide applicable standard 
definitions and reporting timelines to be used and adhered to by the investigators. 
 
 
Definition 
7.1.1 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the medical device.  
 
7.1.2 
Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a serious adverse event 
(SAE). 
 
a)  Led to a death, 
 
b)  Led to a serious deterioration in health of the subject, that either resulted in 
 
1.  a life-threatening illness or injury, or 
2.  a permanent impairment of a body structure or a body function, or 
3. in-patient hospitalization or prolongation of existing hospitalization, or 
4. medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function, or 

 
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5.  chronic disease  
 
c)  Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Note: A planned hospitalization for pre-existing condition, or a procedure required 
by the protocol without a serious deterioration in health, is not considered to be an 
SAE. 
 
7.1.3 
Device Deficiency/Device malfunction  
Device deficiency is defined as an inadequacy of a medical device related to its 
identity, quality, durability, reliability, safety or performance, such as malfunction, 
misuse or use error and inadequate labeling. This includes the failure of the device 
to meet its performance specifications or otherwise perform as intended. Note: 
performance specifications include all claims made in the labeling of the device. 
 
A device malfunction is the failure of a device to meet its performance 
specifications or otherwise perform as intended, when used in accordance with the 
instructions for use or CIP. 
 
 
Device Relationship 
Determination of whether there is a reasonable possibility that a product or device 
caused or contributed to an AE is to be determined by the Investigator and 
recorded on the appropriate source documents and eCRF form. Determination 
should be based on assessment of temporal relationships, evidence of alternative 
etiology, medical/biologic plausibility, and patient condition (pre-existing condition). 
 
 
Adverse Event and Device Deficiency/Device Malfunction Reporting 
7.3.1 
Adverse Event Reporting 
All adverse events will be collected on each subject through the femoral vein 
puncture for transseptal access in preparation for MitraClip System insertion to the 
1-year follow-up visit. Adverse events will not be collected for screen failure 
subjects.  
 

 
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The event course must be monitored until the event has subsided or, in a case of 
permanent impairment, until the event stabilizes and the overall clinical outcome 
has been ascertained. 
 
 
Unchanged, chronic conditions and elective procedures (e.g., routine dental 
procedures) for a pre-existing condition are not considered AEs and should not be 
recorded on the adverse event page of the eCRF.  
 
Non-cardiac related abnormal laboratory values will not be considered AEs unless:  
 
1) the investigator determined that the value is clinically significant,  
2) the abnormal lab value required intervention, or  
3) the abnormal lab value required subject termination from the study. 
 
Serious Adverse Event Reporting:  
 
Serious adverse events, as outlined above, should be reported to the Sponsor, 
EC, and local Food and Drug Administration agency as soon as possible but no 
later than 24 hours from the site becoming aware of the event or as per the 
investigative site’s local requirements if the requirement is more stringent than 
those outlined. 
 
The date the site staff became aware of the SAE must be recorded in the source 
document.  The Investigator will further report the event to the local GCP office 
and the Ethics Committee (EC) according to the institution’s reporting 
requirements.    
 
Serious adverse events, as outlined above, should be reported on the SAE 
Notification Form in the occurrence that the EDC System is not available.  This 
does not replace the EDC reporting system.  All information must still be entered 
in the EDC system once the system is back to normal function. 
  
Study site 
Reporting timelines 
All Sites 
Sites should report SAEs to regulatory authorities and the Sponsor no 
later than 24 hours from the day the site personnel became aware of the 
event or as per the investigative site’s local requirements, if the 
requirement is more stringent than those outlined. 
 
Sites must record the date the site staff became aware that the event met the 
criteria of an SAE in the source document.  The Investigator will further report the 
SAE to the local EC according to the institution’s EC reporting requirements. 

 
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If more detailed information is obtained after the initial reporting, additional report 
shall be prepared and submitted as follow up and/or closing reporting. 
 
7.3.2 
Device Deficiency/Device Malfunction Reporting 
All device deficiencies/malfunctions should be reported within the EDC System on 
the appropriate eCRF form. The investigator should report all device deficiencies 
/malfunctions to the Sponsor as soon as possible but no later than outlined below.  
 
Study site 
Reporting timelines 
All Sites 
Device deficiencies/malfunctions must be reported to the Sponsor no 
later than 2 business days from the day the site personnel became 
aware of the event or as per the investigative site’s local requirements, if 
the requirement is more stringent than those outlined. 
 
Sites must report device deficiencies/malfunctions to the EC per the site’s local 
requirements. 
 
Sites should return the deficiency/malfunction device, if not implanted or not 
remaining in the subject, to the Sponsor.   
 
7.3.3 
Adverse Event Reporting to Regulatory Authorities by the Sponsor  
The Sponsor will report the SAEs and reportable device deficiencies/malfunctions 
to the regulatory authority, per local requirements. The Sponsor will also notify all 
the other study sites conducting the study and ECs of the occurrence of the SAEs.   
  
 
8 
STATISTICAL CONSIDERATIONS 
This is a post market study of consecutive consented, eligible subjects who have 
attempted treatment of the MitraClip System at participating sites. No pre-specified 
hypothesis tests are planned for the MitraClip China PMS. The following section 
describes the statistical methods for the MitraClip China PMS. 

 
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Analysis Populations  
8.1.1 
Attempted Procedure Population (AP) 
The AP population is defined as all subjects registered in the study who have 
MitraClip device placement procedure attempted upon femoral vein puncture for 
transseptal access. 
 
8.1.2 
Implanted Population (IP)  
The implanted population is defined as subjects with MitraClip device implanted. If 
the difference between the AP and IP populations is ≤ 5 subjects, then the 
analysis based on the IP population will not be performed.  
 
 
Statistical Analyses  
Descriptive analysis will be performed to summarize baseline, APS, clinical and safety 
event data.  Depending on the type of data (e.g., continuous or categorical), statistical 
methods described in this section below will be used.  
 
For continuous variables such as age, means, standard deviations, and 95% 
confidence intervals for the mean will be calculated. For binary variables such as 
acute procedure success, counts, percentages, and 95% confidence intervals will 
be calculated.  
 
For time to event data such as all-cause mortality, mitral valve surgery, additional 
MitraClip interventions, Kaplan-Meier analyses will be used. 
 
8.2.1 
Primary Endpoints Analyses 
The study has two primary endpoints: freedom from MAE at 30 days and APS, both 
defined in Section 4.1. 
 
The proportion of subjects experienced MAE at 30 days will be estimated from the 
binomial model. The 95% confidence intervals will be calculated using the exact 
Clopper-Pearson method. Similarly, APS rate will be also estimated from the binomial 
model. The 95% confidence interval will be calculated using the exact Clopper-
Pearson method. Both primary endpoints will be analyzed based on AP and IP (if 
applicable) populations.  

 
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Sample Size Calculations and Assumptions  
A minimum of 50 subjects and a maximum approximately 100 subjects will be 
registered at up to 10 sites. The sample size is determined based on the NMPA 
post approval requirement. 
 
 
Time of Analysis 
The primary endpoint analyses will be performed when all registered subjects 
complete their 30-day follow-up. 
 
9 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Investigator/site will permit direct access to source data/documents for study-
related monitoring, audits, EC review, and regulatory inspections. 
 
Subjects providing informed consent agree to allow Sponsor or designee access 
and copying rights to pertinent information in their medical records concerning their 
participation in this study. The Investigator will obtain, as part of the informed 
consent, permission for study monitors or regulatory authorities to review, in 
confidence, any records identifying the subjects in this study.  This information may 
be shared with regulatory agencies; however, the Sponsor undertakes not to 
otherwise release the subject's personal and private information.  
 
10 QUALITY CONTROL AND QUALITY ASSURANCE 
 Selection of Clinical Sites and Investigators 
The Sponsor will select Investigators who are qualified by training and experience 
and are legally entitled to perform clinical research and to participate in the 
evaluation of the study device.  Sites will be selected based upon review of a recent 
site assessment and the qualifications of the Principal Investigator at the site.  
Investigators will be selected after submission of recent curriculum vitae and 
confirmed 1) has sufficient clinical experience and training for conducting the 
study, 2) has enough time to conduct the study.  The Principal Investigator will 
assign sub-investigators and study collaborators.  All Investigators and study 
collaborators must be trained on the protocol and study procedures prior to 
enrolling subjects.  

 
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In this study, all MitraClip implanters will be designated in advance upon 
consultation with the Principal Investigator of each site.  All MitraClip implanters 
must have undergone the MitraClip Therapy Training program provided by the 
Sponsor. 
 
 Study Finance and Agreements 
Abbott will finance this PMS and will compensate study sites for participation in the 
study per the conditions of agreement between Abbott and the study site. 
 
 Protocol Amendments  
The Sponsor will provide approved protocol amendments to the Investigators prior 
to implementing the amendment. The Principal Investigator is responsible for 
notifying the EC or equivalent committee of the protocol amendment 
(administrative changes) or obtaining EC’s approval of the protocol amendment 
(changes in subject care or safety), according to the instructions provided by the 
Sponsor with the protocol amendment.   
 
Sites must document in writing acknowledgement/approval of the protocol 
amendment by the EC prior to implementation of the protocol amendment. Sites 
must also provide copies of this documentation to the Sponsor. 
 
 Training 
10.4.1 Site Training 
All Investigators/study personnel are required to attend Sponsor training sessions, 
which may be conducted at an Investigator's meeting, a site initiation visit or other 
appropriate training sessions. Training of Investigators/study personnel will 
include, but is not limited to, device training, the protocol requirements, device 
usage, electronic case report form completion, study personnel responsibilities, 
and regulatory requirements.  
 
All Investigators/study personnel that are trained must sign a training log upon 
completion of the training. Prior to signing the training log, Investigator/study 
personnel must not perform any study-related activities that are not considered 
standard of care at the site.  Prior to the initiation of the study, the study monitor or 
designee will visit each site where the study will be conducted.  The study monitor 

 
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will ensure that sites’ study personnel are informed about and understand the study 
requirements.  The following matrix describes the role of study personnel in 
implementing each of the protocol elements. 
 
 
 
 
STUDY ROLE 
 
Protocol Elements 
Study 
Design 
Informed 
Consent 
Process 
Eligibility 
Criteria 
KCCQ 
6MWT 
Distance 
NYHA 
eCRFs 
AE / SAE 
Reporting 
Principal 
Investigator 
 
 
 
 
 
 
 
 
Sub-Investigator  
 
 
 
 
 
 
 
 
Surgeon 
Investigator 
 
 
§ 
 
 
 
 
 
Echocardiographer 
Investigator 
 
 
 
 
 
 
 
 
Study Coordinator  
 
 
 
 
 
 
 
 
 
 = required  
§ = Prohibitive risk for mitral valve surgery eligibility 
 
10.4.2 Training Required for the Use of the Device   
MitraClip implanting investigators will be trained in accordance with the approved 
MitraClip System Instruction for Use (IFU) and established MitraClip Therapy 
Training. Training will include, but will not be limited to, the use of a heart model 
and demonstration unit to ensure that investigators understand the mechanics and 
characteristics of the MitraClip System. Sponsor staff will conduct this training and 
a Training log will be used to document the training. Only physicians who receive 
all required device training, receive an Abbot MitraClip certificate, and complete 
the Training Log can perform the MitraClip procedure under this protocol. The 
Sponsor will be available to provide technical support to answer questions 
regarding the function and operation of the MitraClip System during the MitraClip 
procedure. 
 
The following matrix describes the training requirements for study personnel 
involved in the MitraClip implant procedure at each study site.  The content of each 

 
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of the curricula in the matrix below are described in detail in Sponsor’s operating 
procedures. 
 
 
 
 
 
 
MitraClip PROCEDURE ROLE 
Procedural Role 
Implanter 
Curricula 
Echo 
Curricula 
System 
Preparation 
Curricula 
Implanter 
 
 
 
Echocardiographer 
 
 
 
System preparation personnel  
 
 
 
 = required 
 
 Monitoring 
Sponsor and/or designee will monitor the MitraClip China PMS over its duration 
according to the protocol-specific monitoring plan which will include the planned 
extent of source data verification. 
 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that 
the following criteria are met: 
 
• The investigator understands and accepts the obligation to conduct the 
study according to the protocol and applicable regulations and has signed 
the Clinical Study Agreement  
• The Investigator and his/her staff should have sufficient time and facilities 
to conduct the study and should have access to an adequate number of 
appropriate subjects to conduct the study.  
• Sites must have source documentation (including original medical records) 
to substantiate proper informed consent procedures, adherence to protocol 
procedures, adequate reporting and follow-up of adverse events, accuracy 
of data collected on case report forms, and device information.  

 
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• The Investigator/site will permit access to such records and will maintain a 
monitoring visit sign-in log at the site. The Investigator will agree to dedicate 
an adequate amount of time to the monitoring process. The Investigator 
and/or research coordinator will be available for monitoring visits. It is 
expected that the Investigator will provide the monitor with a suitable 
working environment for review of study-related documents. 
 
 Deviations from Protocol 
The Investigator should not deviate from the protocol for any reason except in 
cases of medical emergencies when the deviation is necessary to protect the 
rights, safety, and well-being of the subject, or to eliminate an apparent immediate 
hazard to the subject. In that event, the Investigator will notify Sponsor immediately 
by phone or in writing.  
 
The Sponsor will not grant any waivers for protocol deviations.  Sites must report 
all deviations to the Sponsor using the Deviation CRF. The Sponsor will monitor 
the occurrence of protocol for evaluation of investigator compliance to the protocol 
and regulatory requirements and handle according to written procedures. 
Investigators will inform their EC or equivalent committee of all protocol deviations 
in accordance with their specific EC or equivalent committee reporting policies and 
procedures.  
 
In the event of repeated non-compliance, as determined by the Sponsor, a 
Sponsor’s monitor or Sponsor’s representative will attempt to secure compliance 
by one or more of the following (and not limited to):  
• Visiting the investigator and/or delegate 
• Telephoning the investigator and/or delegate 
• Corresponding with the investigator and/or delegate 
 
Repeated non-compliance with the signed agreement, the protocol, or any other 
conditions of the study may result in further escalation in accordance with the 
Sponsor’s written procedures, including securing compliance or, at its sole 
discretion, the Sponsor may terminate the investigator's participation in the clinical 
study.  
  

 
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 Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical study 
records, including source documentation, for inspection during a Quality 
Assurance audit.  
 
If an investigator is contacted by a Regulatory Agency in relation to this PMS, the 
Investigator will notify Sponsor immediately. The Investigator and Research 
Coordinator must be available to respond to reasonable requests and audit queries 
made during the audit process. The Investigator must provide the Sponsor with 
copies of all correspondence that may affect the review of the current study. The 
Sponsor may provide any needed assistance in responding to regulatory audits. 
 
 Sponsor Auditing 
The Sponsor shall prepare an audit plan as well as the operating procedures for 
the related duties and conduct audits in accordance with the audit plan and the 
operating procedures. 
 
Individual engaged in auditing (hereinafter referred to as "auditor") shall be different 
than those in charge of medical device development or monitoring. 
 
The auditor shall prepare an audit report documenting the matters confirmed in the 
audit to certify and verify that the audit has been conducted and submit them to the 
Sponsor. 
 
 Primary Investigator Responsibilities 
The responsibilities of the Primary Investigator shall be as follows coordinating 
among all clinical sites during the clinical trial, organizing investigator meetings at 
the earlier stage, middle stage and later stage of the trial, and implementing the 
entire trial together with the sponsor in China and complete the summary report 
in coordination with the investigators of all the participating investigating sites. 
 
11 DATA HANDLING AND RECORD KEEPING 
Sponsor and/or its affiliates will maintain documentation of the systems and 
procedures used in data collection for the duration of the study.  
 

 
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CRF data collection will be performed through a secure web portal and only 
authorized personnel will access the EDC system using a unique username and 
password to enter, review or correct data. Passwords and electronic signatures 
will be strictly confidential.   
 
The data will be subjected to consistency and validation checks within the EDC 
system and supplemental review by the Sponsor.    
 
At the end of the study, completed CRF images with the date-and-time stamped 
electronic audit trail indicating the user, the data entered, and any reason for 
change will be provided to the study sites, if requested.  
 
For the duration of the study, the Investigator will maintain complete and accurate 
documentation including, but not limited to, medical records, study progress 
records, laboratory reports, CRFs, signed ICFs, correspondence with the EC and 
study monitor/Sponsor, adverse event reports, and information regarding subject 
discontinuation or completion of the study. 
 
 Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or 
maintained for this study.  
 
The Sponsor implements technical and physical access controls to ensure that 
Personal Information is accessible only to and processed only on a ‘need to know’ 
basis, including periodic review of access rights, and revocation of access when 
an individual’s employment is terminated or the individual transitions to a role that 
does not require access to Personal Information, and appropriate restrictions on 
physical access to premises, facilities, equipment, and records containing 
Personal Information. 
 
The Sponsor requires the study sites to enter only pseudonymous Personal 
Information (key-coded) necessary to conduct the study, such as the patient’s 
medical condition, treatment, dates of treatment, etc., into Sponsor’s data 
management systems. The Sponsor discloses as part of the study informed 
consent process that some Sponsor representatives still may see Personal 
Information at the participating sites for technical support of the participating 
physicians on the device implant or procedures, monitoring and quality control 
purposes. All parties will observe confidentiality of Personal Information always 
throughout the study. All reports and data publications will preserve the privacy of 
each subject and confidentiality of his/her information. 

 
ABT-CIP-10263 Ver. D 
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The Sponsor data management systems and processes were designed, 
developed, and tested according to industry standards to appropriately safeguard 
Confidential Information (including any Personal Information) against unauthorized 
access and/or interference by third parties, intrusion, theft, destruction, loss or 
alteration. Study data are encrypted in transit and at rest.  
 
The Sponsor maintains a Privacy Incident procedure that complies in all respects 
with Applicable Law and industry best practices. 
 
 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, 
data cleaning, and issuing and resolving data discrepancies. If appropriate, the 
DMP may be updated throughout the duration of the study. The Sponsor will track 
and document control all revisions. 
 
 Source Documentation 
Regulations and GCP require the Investigator to maintain information in the 
subject’s original medical records that corroborates data collected on the CRFs. 
To comply with these regulatory requirements/GCP, sites should include the 
following information in the subject record at a minimum and if applicable to the 
clinical study: 
• Medical history/physical condition of the subject before involvement in the 
study sufficient to verify protocol entry criteria 
• Dated and signed notes on the day of entry into the clinical study 
referencing the Sponsor, protocol number, subject ID number, and a 
statement that informed consent was obtained 
• Dated and signed notes from each subject visit (for specific results of 
procedures and exams) 
• AEs reported and their resolution, including supporting documents, such 
as discharge summaries, catheterization laboratory reports, ECGs, and 
lab results including documentation of site awareness of SAEs and of 
investigator assessment of device relationship for SAEs. 

 
ABT-CIP-10263 Ver. D 
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• Protocol-required laboratory reports and 12-lead ECGs, reviewed and 
annotated for clinical significance of out of range results (if applicable).  
• Notes regarding protocol-required and prescription medications taken 
during the study (including start and stop dates) 
• Subject’s condition upon completion of or withdrawal from the study 
• Any other data required to substantiate data entered into the CRF 
• Patient reported outcome measures may be completed using CRF 
worksheets. This serves as source documentation. 
 
 Electronic Case Report Form Completion 
Site research personnel trained on the protocol and CRF completion will perform 
the primary data collection clearly and accurately based on source-documented 
hospital and/or clinic chart reviews. The investigator will ensure accuracy, 
completeness, legibility, and timeliness of the data reported to the Sponsor on the 
CRFs and in all required reports. 
 
eCRF data will be collected for all subjects who are registered into the study. 
 
Only authorized site personnel will be permitted to enter the CRF data through 
the EDC system deployed by the Sponsor. The Sponsor will use an electronic 
audit trail to track any subsequent changes of the entered data. 
 
The following data elements will be collected on eCRFs: 
Visit 
Data Elements to be Collected 
Screening  
- Document medical history 
- Weight, temperature, blood pressure and heart rate 
- MR severity, MVA and etiology (Functional or Degenerative) 
based on TTE/TEE  
- Left ventricular ejection fraction and left ventricular end-
systolic dimension based on TTE  
- Mitral valve anatomy for MitraClip suitability  
Baseline (within 14 days prior to 
subject registration) 
- Document medical history 
- Weight, temperature, blood pressure and heart rate 
- STS Mortality Risk Score for mitral valve replacement 
- EuroScore II 
- MR severity, MVA and etiology (Functional or Degenerative) 
based on TTE/TEE (screening TTE/TEE can be used if 
within 14 days) 
- KCCQ 
- NYHA Classification 

 
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Visit 
Data Elements to be Collected 
- Pregnancy test for females of childbearing potential 
- Blood test (CBC with differentials and platelet count, serum 
creatinine, urea, CK and CK-MB, BNP and NT-proBNP) 
- Cardiac medications  
Pre-Procedure (within 24 hours 
prior to subject registration) 
- 12-Lead ECG 
- Weight, temperature, blood pressure and heart rate 
- ACT and administration of anticoagulation therapy  
Procedure  
- ACT and administration of anticoagulation therapy 
- Model and serial number of devices used (whether or not 
implanted) 
- Number of devices implanted (if implant unsuccessful, 
reason for unsuccessful implant)  
- Procedure and Device times 
- Length of stay in ICU/CCU/PACU post-procedure 
Discharge 
- MR severity based on TTE 
- Weight, temperature, blood pressure and heart rate 
- Blood test (CBC with differentials and platelet count, serum 
creatinine, urea, CK and CK-MB, BNP and NT-proBNP) 
- Cardiac medications 
Follow-up (30 days and 1 year) 
- MR severity based on TTE 
- KCCQ 
- NYHA Classification 
- Six Minute Walk Test Distance (excluding 30 days) 
- Weight, temperature, blood pressure and heart rate 
- Blood test (CBC with differentials and platelet count, serum 
creatinine, urea, CK and CK-MB, BNP and NT-pro-BNP) 
- Cardiac medications 
Throughout follow-up 
Adverse events, device complications or malfunctions, 
hospitalizations, additional MitraClip procedures, mitral valve 
surgery, and protocol deviations will be reported as they occur 
 
 Record Retention 
 The Investigator/Site will archive and retain all documents pertaining to the study 
until 10 years after the completion of the study as per the applicable regulatory 
record retention requirements. The Investigator/Site must obtain permission from 
Sponsor in writing before destroying or transferring control of any study records. 
The Sponsor shall keep the study data until the medical device are withdrawn. 
 

 
ABT-CIP-10263 Ver. D 
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12 ETHICAL CONSIDERATION  
 Ethics Committee Review and Approval 
The Principal Investigator at each study site will obtain EC approval for the protocol 
and ICF/other written information provided to the patient prior to consenting and 
registering patients in this clinical study. The site must receive the approval letter 
prior to the start of this clinical study and provide a copy to the Sponsor.  
 
Sites will submit any amendments to the protocol as well as associated ICF 
changes to the EC and written approval obtained prior to implementation, 
according to each institution’s EC requirements.  
 
No changes will be made to the protocol or ICF or other written information 
provided to the patient without appropriate approvals, including EC, the Sponsor, 
and the regulatory agencies (if applicable).  
 
Until the clinical study is completed, the Investigator will advise his/her EC of the 
progress of this study, per EC requirements. Written approval must be obtained 
from the EC yearly to continue the study, or according to each institution’s EC 
requirements.  
 
Sites will not perform any investigative procedures, other than those defined in this 
protocol, on the registered subjects without the written agreement of the EC and 
the Sponsor. 
 
13 CLINICAL STUDY CONCLUSION 
The clinical study will be concluded when: 
• All sites are closed AND 
• The final report has been provided to investigators or the Sponsor has 
provided formal documentation of study closure. 
 
14 PUBLICATION POLICY 
The data and results from the PMS are the sole property of the Sponsor. The 
Sponsor shall have the right to access and use all data and results generated 
during the PMS. The Investigators will not use this study-related data without the 
written consent of the Sponsor for any purpose other than for clinical study 

 
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completion or for generation of publication materials, as referenced in the Clinical 
Study Agreement. Single-center results are not allowed to be published or 
presented before the multi-center results. The Sponsor must review and approve 
any proposals for publications or presentations by the investigators in a timely 
manner in compliance with the Sponsor’s publication policy set forth in the Clinical 
Study Agreement. 
 
The Sponsor will be responsible for determining whether to register the study on 
www.clinicaltrials.gov or any other clinical trials, in accordance with the 
International Committee of Medical Journal Editors guidelines, or any other 
applicable guidelines. In the event the Sponsor determines that the study should 
be registered, the Sponsor shall be responsible for any such registration and 
results posting as required by the ClinicalTrials.gov website. Institution and/or 
Principal Investigator(s) shall not take any action to register the study. 
15 RISK ANALYSIS 
Patients with symptomatic MR who are difficult for mitral valve surgery have limited 
therapeutic options. Patients judged difficult for surgery with untreated moderate-
to-severe or severe MR present with a high rate of heart failure hospitalizations, 
poor quality of life, and impaired functional capacity.   
 
 
In the context of accumulated evidence worldwide, the MitraClip China PMS 
serves as a bridge to previous clinical data.  Based on the available data, it is likely 
that the benefits significantly outweigh any potential risks to symptomatic MR 
patients in China.  
 
 Anticipated Clinical Benefits 
Prior clinical data have shown that the MitraClip System is associated with vast 
improvements in overall MR symptomatology, demonstrated to be both clinically 
and statistically significant.  Potential benefits of the MitraClip System include, but 
may not be limited to, the following: 
 
• 
Reduction in heart failure hospitalization rates 
• 
Improved symptomatic status and functional capacity 
• 
Improved quality of life 
• 
Improved NYHA classification 
• 
Improved LV function associated with reverse left ventricular remodeling 
(i.e., LVEDV) 

 
ABT-CIP-10263 Ver. D 
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• 
Reduced mortality 
 Foreseeable Adverse Events and Anticipated Adverse Device Effects   
Per the MitraClip System IFU, the anticipated events on Table 15-1 have been 
identified as possible.  
Table 15-1: Potential Complications and Adverse Events (MitraClip System IFU) 
Allergic reaction (anesthetic, contrast, Heparin, 
nickel alloy, latex) 
Aneurysm or pseudo-aneurysm 
Arrhythmias 
Atrial fibrillation 
Atrial septal defect requiring intervention 
Arterio-venous fistula 
Bleeding 
Cardiac arrest 
Cardiac perforation 
Cardiac tamponade / Pericardial Effusion 
Chordal entanglement/rupture 
Coagulopathy 
Conversion to standard valve surgery 
Death 
Deep venous thrombus (DVT) 
Dislodgement of previously implanted devices 
Dizziness 
Drug reaction to anti-platelet / anticoagulation 
agents / contrast media 
Dyskinesia 
Dyspnea 
Edema 
Emboli (air, thrombus, MitraClip Implant) 
Emergency cardiac surgery 
Endocarditis 
Esophageal irritation 
Esophageal perforation or stricture 
Failure to deliver MitraClip to the intended site 
Failure to retrieve MitraClip System components 
Fever or hyperthermia  
Gastrointestinal bleeding or infarct 
Hematoma 
Hemolysis 
Hemorrhage requiring transfusion 
Hypotension / hypertension 
Infection 
Lymphatic complications 
Mesenteric ischemia 
Mitral stenosis 
Mitral valve injury 
MitraClip Implant erosion, migration or malposition 
MitraClip Implant thrombosis 
MitraClip System component(s) embolization 
Multi-system organ failure 
Myocardial infarction 
Nausea/vomiting 
Pain 
Peripheral ischemia 
Prolonged angina 
Prolonged ventilation 
Pulmonary congestion 
Pulmonary thrombo-embolism 
Renal insufficiency or failure 
Respiratory failure / atelectasis / pneumonia 
Septicemia 
Shock, Anaphylactic or Cardiogenic 
Single leaflet device attachment (SLDA) 
Skin injury or tissue changes due to exposure to 
ionizing radiation 
Stroke or transient ischemic attack (TIA) 
Urinary tract infection 
Vascular trauma, dissection or occlusion 
Vessel spasm 
Vessel perforation or laceration 
Worsening heart failure 
Worsening mitral regurgitation 
Wound dehiscence 
 
 Residual Risk Associated with MitraClip System 
This is a PMS on an NMPA approved commercially available device. There is no 
investigational device being used as part of this study.   

 
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 Risk Associated with Participation in This Study 
Treatment with the MitraClip device as part of this study is identical to treatment 
with the MitraClip device outside of this study. Participation in the study will not 
impact the MitraClip procedure or use of the MitraClip device in any way. 
Participation in the study requires submission of data that may or may not be 
protected heath information. This information should be kept confidential, but there 
is a risk that some of the information could be unintentionally made non-
confidential. The risk of this happening for this study is no greater than the risk of 
loss of confidentiality in any study.   
 
 Possible interaction with Protocol-Required Concomitant Medications 
This is a post-market study being conducted under standard of care medications. 
There are no protocol-required medications being used as part of this study.  
  
 Steps Taken to Control or Mitigate Risks 
Per the MitraClip System IFU, “Use of the MitraClip Delivery System should be 
restricted to those physicians trained to perform invasive endovascular and 
transseptal procedures and to those physicians trained in the proper use of the 
system”.    
 
Risks associated with the use of the device during this clinical study are minimized 
through device design, investigator selection and training, pre-specified patient 
eligibility requirements. 
 
The contraindications, warnings and precautions are listed in the MitraClip System 
IFU that will be provided with all devices to be used during this study.  
 
 Risk to Benefit Rationale 
Patients with symptomatic MR have limited therapeutic options. Patients judged 
difficult for surgery with untreated moderate-to-severe or severe MR present with 
a high rate of heart failure hospitalizations, poor quality of life, and impaired 
functional capacity.   
 

 
ABT-CIP-10263 Ver. D 
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The MitraClip System provides patients with a minimally invasive, safe option to 
reduce MR that affords short recovery times with amelioration of symptoms, and a 
resulting improvement in both cardiac function and quality of life. 
 
The risk-benefit profile of the MitraClip System has been established in patients 
with moderate to severe and severe DMR or FMR, who may be high surgical risk 
candidate per the EVEREST family and COAPT trials, and has been further 
demonstrated through the European commercial experience, including ACCESS-
EU and national registries such as TRAMI, GRASP and EXPAND. In total, over 
100,000 patients have been treated with the MitraClip system worldwide. 
 
All protocol required clinical assessments are standard assessments for most 
cardiac/structural heart interventional procedures, and will be administered per 
standard of care at each Institution. As such these assessments do not involve 
additional risks to the trial participants. Per protocol required concomitant 
anticoagulation and antiplatelet medications should be administered as described 
in the drug summary of product characteristics. 
 
Subjects participating in the study have a small risk of loss of confidentiality as part 
of the data collection process. This risk is mitigated to as low as possible with the 
use of data collection systems, methods and procedures that are used commonly 
in clinical research. This includes the use of only validated electronic systems, the 
training of study personnel and the use of de-identified data for all data entry. 
Based upon the established safety profile of the MitraClip implant; the low risk of 
loss of confidentiality is adequately mitigated to justify use of the MitraClip implant 
to treat patients for this study. 
 
 
 

 
ABT-CIP-10263 Ver. D 
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PMS 
 
 
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16 APPENDICES 
 Appendix I: Abbreviations and Acronyms 
Acronym or Abbreviations 
Complete Phrase or Definition 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
APS 
Acute Procedural Success 
ASA 
Acetylsalicylic Acid 
ASD 
Atrial Septal Defect 
BNP and NT-proBNP 
Brain Natriuretic Peptide and N-Terminal Pro-B 
Type Natriuretic Peptide 
CBC 
Complete Blood Count 
CCU 
Critical Care Unit 
CDS 
Clip Delivery System 
CE 
Conformité Européenne (EU) 
CIP 
Clinical Investigational Plan 
CK-MB 
Creatinine Kinase-MB 
CRT 
Cardiac Resynchronization Therapy 
CRT-D 
Cardioverter Defibrillator 
CT 
Cardiothoracic 
DD 
Device Deficiency 
DDCD 
Duke Databank of Cardiovascular Disease 
DM 
Device Malfunction 
DMR 
Degenerative Mitral Regurgitation 
DVT 
Deep Vein Thrombosis 
EC 
ECG 
Ethics Committee 
Electrocardiogram 
ECL 
Echocardiography Core Laboratory 
eCRF 
Electronic CRF 
EDC 
Electronic Data Capture 
EF 
Ejection Fraction 
FMR 
Functional Mitral Regurgitation 
HRR 
High Risk Registry 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
ICMJE 
International Committee of Medical Journal 
Editors 
ICU 
Intensive Care Unit 
IFU 
Instructions for Use 

 
ABT-CIP-10263 Ver. D 
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LBBB 
Left Bundle Branch Block 
LV 
Left Ventricle or Left Ventricular 
LVEDD 
Left Ventricular End Diastolic Dimension 
LVEDV 
Left Ventricular End Diastolic Volume 
LVESD 
Left Ventricular End Systolic Dimension 
LVESV 
Left Ventricular End Systolic Volume 
LVEF 
Left Ventricular Ejection Fraction 
MAE 
Major Adverse Events 
MI 
Myocardial Infarction 
MLWHF 
Minnesota Living with Heart Failure 
MOPs 
Manual of Operations 
MR 
Mitral Regurgitation 
NYHA 
New York Heart Association 
PACU 
Post-Anesthesia Care Unit 
PE 
Product Experience 
PMS 
Post Market Study 
QoL 
Quality of Life 
RCT 
Randomized Clinical Trial 
SLDA 
Single Leaflet Device Attachment 
STS 
Society of Thoracic Surgeons 
TAVR 
Transcatheter aortic valve replacement 
TEE 
Transesophageal Echocardiogram 
TTE 
Transthoracic Echocardiogram 
UFH 
Unfractionated Heparin 
ULN 
Upper Limit of Normal 
VARC 
Valve Academic Research Consortium 
 
 
 

 
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 Appendix II: Definitions 
The following definitions will be used in the MitraClip China protocol.   
 
ADVERSE EVENT 
An adverse event (AE) is any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects (including events related to the procedures involved), users or other 
persons, whether or not related to the medical device. For users or other 
persons, this definition is restricted to events related to medical devices. 
 
 
ANTICIPATED ADVERSE EVENT 
Abbott Clinical definition (derived from ISO14155, MEDDEV 2.7.3): an effect which 
by its nature, incidence, severity or outcome has been previously identified in the 
risk analysis report, as documented in the IFU or study protocol. 
 
ATRIAL FIBRILLATION (AF) 
Heart Rhythm Society Guidelines 
Paroxysmal: Recurrent (≥ 2) atrial fibrillation episodes that terminate 
spontaneously within 7 days. 
 
Persistent:  Atrial fibrillation that is sustained beyond 7 days or lasting less 
than 7 days but necessitating pharmacologic or electrical cardioversion. 
 
Longstanding Persistent AF: Continuous atrial fibrillation of greater than 1-
year duration. 
 
Permanent:  Atrial fibrillation in which cardioversion has failed or not been 
attempted.  
 
ATRIAL SEPTAL DEFECT 
Defect (‘hole’) in the septum between the left and right atria; considered clinically 
significant if it requires percutaneous or surgical intervention (repair of ASD 
completed at the time of surgery for other reasons, but not as the primary reason 
for surgery, is not counted as ASD.) 
 
CHRONIC MITRAL REGURGITATION 
Mitral regurgitation persisting for a long time or constantly recurring; having a slow 
progressive course of indefinite duration (e.g., non-acute) 
 

 
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DEATH 
Defined as all causes of death for the primary safety Major Adverse Event (MAE) 
Endpoint.  Death is further divided into 2 categories 
 
1. CARDIOVASCULAR DEATH (VARC) 
Cardiovascular death is defined by the Valve Academic Research Consortium 
(VARC)5 as any one of the following: 
 
• Any death due to proximate cardiac cause (e.g. MI, cardiac tamponade, 
worsening heart failure) 
 
• Unwitnessed death and death of unknown cause 
 
• All procedure-related deaths, including those related to a complication of 
the procedure or treatment for a complication of the procedure 
 
• Death caused by non-coronary vascular conditions such as 
cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, 
dissecting aneurysm, or other vascular disease 
 
2. NON-CARDIOVASCULAR DEATH 
Any death not covered by the definitions for Cardiovascular Death, such as death 
caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide, or 
trauma.  
 
 
DEVICE EMBOLIZATION 
Detachment of the deployed MitraClip device from both mitral leaflets 
 
DEVICE THROMBOSIS 
Evidence of the formation of an independently moving thrombus on any part of the 
MitraClip device evidenced by echocardiography or fluoroscopy.  If the MitraClip 
device is explanted or an autopsy is performed, this diagnosis should be 
confirmed. 
 
ENDOCARDITIS 
Defined as a diagnosis of endocarditis based on the following Duke criteria. 
 
Duke Criteria  
(From The ACC/AHA Guidelines for the Management of Patients with Valvular 
Heart Disease, JACC, Vol 32, No.5, November 1, 1998:pg1541, Table 21) 

 
ABT-CIP-10263 Ver. D 
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Pathological Criteria 
 
Microorganisms: culture or histology in a vegetation, in a vegetation that 
has embolized, or in an intracardiac abscess, or  
 
Pathological lesions: vegetation or intracardiac abscess present, confirmed 
by histology showing active endocarditis 
 
OR 
 
Clinical Criteria 
 
Major Criteria 
Persistently positive blood cultures: 
Typical organisms for endocarditis: Streptococcus viridans, S bovis, 
“HACEK” group, community acquired Staphylococcus aureus or 
enterococci, in the absence of a primary focus  
Persistent bacteremia:  
≥ 2 positive cultures separated by ≥12 hours or ≥ 3 positive cultures ≥ 
1 h apart or 70% blood culture samples positive if ≥ 4 are drawn 
Evidence of endocardial involvement 
Positive echocardiogram 
Oscillating vegetation 
Abscesses 
Valve perforation 
New partial dehiscence of prosthetic valve 
New valvular regurgitation 
 
Minor Criteria 
Predisposing heart condition: 
MVP, bicuspid aortic valve, rheumatic or congenital heart disease, 
intravenous drug use  
Fever 
Vascular phenomena:  
Major arterial emboli, septic pulmonary emboli, mycotic aneurysm, 
intracranial hemorrhage, Janeway lesions 
Immunologic phenomena 
Glomerulonephritis, Osler's nodes, Roth spots , and rheumatoid factor 
Positive blood culture: not meeting major criteria  
Echocardiogram: positive but not meeting major criteria 
 
Diagnosis 

 
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2 major criteria or 
1 major plus 3 minor criteria or 
5 minor criteria 
 
ETIOLOGY OF MITRAL REGURGITATION 
Etiology of mitral regurgitation will be determined as either Degenerative or 
Functional:  
 
1. DEGENERATIVE MITRAL REGURGITATION 
Mitral regurgitation primarily due to abnormality of the mitral apparatus 
 
2. FUNCTIONAL MITRAL REGURGITATION 
Global or regional left ventricular wall motion abnormalities causing leaflet 
restriction or tethering with or without dilatation of the mitral annulus, but 
with no significant abnormalities of the mitral leaflet 
 
GASTROINTESTINAL COMPLICATIONS 
Complications as a result of the MitraClip procedure affecting the gastrointestinal 
tract requiring surgery.  May include fecal impaction, bowel obstruction, etc. 
 
HOSPITALIZATION (ALL-CAUSE) 
Defined as admission to inpatient unit or ward in the hospital for at least 24 hours, 
including emergency department stay.  Excludes hospitalizations planned for pre-
existing conditions unless there is worsening in the baseline condition.  
 
HEART FAILURE HOSPITALIZATION 
Defined as an event that meets the following criteria:  
 
A. Requires hospitalization with treatment in any inpatient unit or ward in the 
hospital for at least 24 hours, including emergency department stay,  
 
AND 
 
B. Subject has clinical signs and/or symptoms of heart failure, including new or 
worsening dyspnea, orthopnea, paroxysmal nocturnal dyspnea, increasing 
fatigue, worsening functional capacity or activity intolerance, or signs and/or 
symptoms of volume overload,  
 
AND 
 
C. Results in intravenous (e.g., diuretic or vasoactive therapy) or invasive (e.g., 
ultrafiltration, IABP, mechanical assistance) treatment for heart failure.  

 
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For the purpose of the protocol, overnight stays at nursing home facilities, physical 
rehab or extended care facilities, including hospice, do not meet the protocol 
definition of hospitalization.   
 
OTHER CARDIOVASCULAR HOSPITALIZATION 
Defined as treatment in any inpatient unit or ward in the hospital for at least 24 
hours, including emergency department stay for conditions such as coronary artery 
disease, acute myocardial infarction, hypertension, cardiac arrhythmias, 
cardiomegaly, pericardial effusion, atherosclerosis and peripheral vascular 
disease, not related to heart failure as defined. 
 
NON-CARDIOVASCULAR HOSPITALIZATION 
Hospitalizations that are not heart failure or other cardiovascular hospitalizations, 
as defined above, will be categorized as non-cardiovascular hospitalizations. 
 
MAJOR BLEEDING  
Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding 
Academic Research Consortium (BARC)6 definition:
• 
Type 3  
o Type 3a  
 
Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* 
(provided  hemoglobin drop is related to bleed)  
 
Any transfusion with overt bleeding 
o Type 3b  
 
Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided 
hemoglobin drop is related to bleed)  
 
Cardiac tamponade 
 
Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid) 
 
Bleeding requiring intravenous vasoactive agents 
o Type 3c  
 
Intracranial hemorrhage (does not include microbleeds or 
hemorrhagic transformation, does include intraspinal) 
 
Subcategories confirmed by autopsy or imaging or lumbar 
puncture 
 
Intraocular bleed compromising vision 
• 
Type 4: CV Surgery-related bleeding  
o Perioperative intracranial bleeding within 48 h 
o Reoperation after closure of sternotomy for the purpose of controlling 
bleeding 

 
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o Transfusion of ≥5 U whole blood or packed red blood cells within a 
48-h period† 
o Chest tube output ≥2L within a 24-h period 
• 
Type 5: Fatal bleeding  
o Type 5a  
 
Probable fatal bleeding; no autopsy or imaging confirmation 
but clinically suspicious 
o Type 5b  
 
Definite fatal bleeding; overt bleeding or autopsy or imaging 
confirmation  
*Corrected for transfusion (1 U packed red blood cells or 1 U whole blood=1 
g/dL hemoglobin) 
†Cell saver products are not counted 
 
 
MAJOR VASCULAR COMPLICATION 
Any major complication, relating to, or affecting, the circulatory system as a result 
of the MitraClip procedure, including new onset of any of the following:   
• 
Hematoma at access site >6 cm.; 
• 
Retroperitoneal hematoma; 
• 
Arterio-venous fistula; 
• 
Symptomatic peripheral ischemia/ nerve injury with clinical signs or 
symptoms lasting >24 hours;  
• 
Vascular surgical repair at catheter access sites;  
• 
Pulmonary embolism; 
• 
Ipsilateral deep vein thrombus; or 
• 
Access site-related infection requiring intravenous antibiotics and/or 
extended hospitalization. 
 
MITRAL VALVE STENOSIS 
Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the 
Echocardiography Core Laboratory. 
 
MYOCARDIAL INFARCTION 
Myocardial infarction (MI) classification and criteria for diagnosis is defined as 
follows:  
 
Peri-procedural MI (≤ 72 hours after MitraClip procedure) 
Mandatory: CK-MB (preferred) ≥10x ULN within 72 hrs. post-MitraClip 
procedure in patient with normal baseline CK-MB  
 
OR 

 
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Mandatory: CK-MB ≥5x ULN within 72 hrs. post-MitraClip procedure in patient 
with normal baseline CK-MB plus new pathological Q-waves in ≥2 contiguous 
leads, or new LBBB  
 
Post-surgery 
Mandatory: CK-MB ≥10x ULN (preferred) within 24 hrs. of cardiothoracic 
surgery plus 1 of the following: 
 
• 
New pathological Q-waves in ≥2 contiguous leads or new persistent 
LBBB on ECG ≥30 min. and ≤72 hrs. post-CABG cardiothoracic surgery, 
or 
• 
New substantial wall motion abnormalities by imaging except new septal 
or apical abnormalities. 
 
Spontaneous MI (>72 hours after MitraClip procedure)  
Any one of the following criteria: 
 
• 
Detection of rise and/or fall of cardiac biomarkers (CK-MB) with at least 
one value above the upper limits of normal (ULN), together with 
evidence of myocardial ischemia with at least one of the following:  
— ECG changes indicative of new ischemia [new ST-T changes or 
new left bundle branch block (LBBB)] 
— New pathological Q waves in at least two contiguous leads 
— Imaging evidence of new loss of viable myocardium or new wall 
motion abnormality 
• 
Sudden, unexpected cardiac death, involving cardiac arrest, often with 
symptoms suggestive of myocardial ischemia, and accompanied by 
presumably new ST elevation, or new LBBB, and/or evidence of fresh 
thrombus by coronary angiography and/or at autopsy, but death 
occurring before blood samples could be obtained, or at a time before 
the appearance of cardiac biomarkers in the blood. 
• 
Pathological findings of an acute myocardial infarction. 
 
NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA CLASS) 
 
Class I 
Patients with cardiac disease but without resulting limitations of 
physical activity. 
Class II 
Patients with cardiac disease resulting in slight limitation of 
physical activity.  Patients are comfortable at rest.  Ordinary 
physical activity results in fatigue, palpitation, dyspnea, or 
anginal pain. 

 
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Class III 
Patients with cardiac disease resulting in marked limitation of 
physical activity.  Patients are comfortable at rest.  Less than 
ordinary physical activity causes fatigue, palpitation dyspnea, 
or anginal pain. 
Class IV 
Patients with cardiac disease resulting in inability to carry on 
any physical activity without discomfort.  Symptoms of cardiac 
insufficiency or of the anginal syndrome may be present even 
at rest.  If any physical activity is undertaken, discomfort is 
increased. 
 
 
NON-ELECTIVE 
(i.e., 
URGENT 
or 
EMERGENT) 
CARDIOVASCULAR 
SURGERY FOR PROCEDURE OR DEVICE RELATED EVENTS 
Cardiovascular surgical procedure performed for device related complication 
requiring surgery within 24 hours of onset of adverse event.  If non-urgent surgery 
was performed within 24 hours of the onset of the adverse event but was not 
required within this timeframe, it will not be considered “non-elective”.   Examples 
of Device Related Complications are myocardial perforation, Single Leaflet Device 
Attachment, embolization of the MitraClip device or MitraClip System components, 
iatrogenic atrial septal defect, or the need for mitral valve replacement instead of 
repair due at least in part to the MitraClip procedure or the presence of the 
MitraClip device. 
 
SERIOUS ADVERSE EVENT (SAE) 
A serious adverse event is defined as an event: 
 
a)  Led to a death, 
 
b)  Led to a serious deterioration in health of the subject, that either resulted in 
 
1.  a life-threatening illness or injury, or 
2.  a permanent impairment of a body structure or a body function, or 
5. in-patient hospitalization or prolongation of existing hospitalization, or 
6. medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function, or 
5.  chronic disease  
 
c)  Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 

 
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A planned hospitalization for pre-existing condition, or a procedure required by 
the protocol, without a serious deterioration in health, is not considered to be a 
serious adverse event. 
 
SINGLE LEAFLET DEVICE ATTACHMENT (SLDA) 
Defined as unilateral MitraClip detachment from one leaflet, as assessed by the 
Echocardiography Core Laboratory or during mitral valve surgery.  Reasons for 
MitraClip Detachment include leaflet tearing, MitraClip unlocking, MitraClip fracture or 
inadequate MitraClip placement.  Not included are any fractures or other failures of 
the MitraClip that do not result in MitraClip detachment from one or both leaflets.   
 
STROKE and TIA 
Stroke is defined as an acute episode of focal or global neurological dysfunction 
caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or 
infarction.  Stroke may be classified as ischemic or hemorrhagic with appropriate 
sub-definitions.  Ischemic stroke is defined as an acute episode of focal cerebral, 
spinal, or retinal dysfunction caused by infarction of central nervous system tissue.  
Hemorrhagic stroke is defined as an acute episode of focal or global cerebral or 
spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid 
hemorrhage.  A stroke may be classified as undetermined if there is insufficient 
information to allow categorization as ischemic or hemorrhagic. 
 
An entity closely related to ischemic stroke is transient ischemic attack (TIA).  TIA 
is defined as a transient episode of focal neurological dysfunction caused by brain, 
spinal cord, or retinal ischemia, without acute infarction.  The difference between 
TIA and ischemic stroke is the presence of infarction.  In the absence of affirmative 
evidence confirming the presence or absence of infarction, a symptom duration of 
24 hours will be used to distinguish TIA from ischemic stroke.  By definition, TIA 
does not produce lasting disability. 
 
 
Although imaging (typically, MRI for acute and chronic ischemia and hemorrhage, 
and CT for acute and chronic hemorrhage and chronic ischemia) is often used to 
supplement the clinical diagnosis of stroke, a diagnosis of stroke may be made on 
clinical grounds alone.   
 
Diagnostic criteria 
 
Acute episode of a focal or global neurological deficit with at least one of the 
following: change in level of consciousness, hemiplegia, hemiparesis, 
numbness or sensory loss affecting one side of the body, dysphasia or 

 
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aphasia, hemianopia, amaurosis fugax, or other neurological signs or 
symptoms consistent with stroke 
 
Stroke – Duration of a focal or global neurological deficit ≥24 h; OR <24 h if 
available neuroimaging documents a new hemorrhage or infarct; OR the 
neurological deficit results in death 
 
TIA – Duration of a focal or global neurological deficit <24 h, any variable 
neuroimaging does not demonstrate a new hemorrhage or infarct 
 
No other readily identifiable non-stroke cause for the clinical presentation (e.g. 
brain 
tumor, 
trauma, 
infection, 
hypoglycemia, 
peripheral 
lesion, 
pharmacological influences), to be determined by or in conjunction with 
designated neurologist* 
 
Confirmation of the diagnosis by at least one of the following: 
– Neurologist or neurosurgical specialist 
– Neuroimaging procedure (CT scan or brain MRI), but stroke may be 
diagnosed on clinical grounds alone 
Stroke classification 
 
Ischemic – An acute episode of focal cerebral, spinal, or retinal dysfunction 
caused by infarction of central nervous system tissue 
 
Hemorrhagic – An acute episode of focal or global cerebral or spinal 
dysfunction caused by intraparenchymal, intraventricular, or subarachnoid 
hemorrhage 
 
A stroke may be classified as undetermined if there is insufficient information 
to allow categorization as ischemic or hemorrhagic 
* Patients with non-focal global encephalopathy will not be reported as a stroke 
without unequivocal evidence of cerebral infarction based upon neuroimaging 
studies (CT scan or Brain MRI). 
 
 
RENAL FAILURE 
New need for dialysis or a creatinine increasing to 3.5 mg/dL or greater 
Note: Increase of creatinine less 1.0 mg/dL over baseline is NOT considered renal 
failure 
 

 
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SYMPTOMATIC MITRAL REGURGITATION 
Symptomatic refers to limitation of physical activity (i.e. NYHA Classification II, III 
or IV) 
 
VULNERABLE POPULATION (ISO14155 Definition) 
Individuals with lack of or loss of autonomy due to immaturity or through mental 
disability, persons in nursing homes, children, impoverished persons, subjects in 
emergency situations, ethnic minority groups, homeless persons, nomads, 
refugees, and those incapables of giving informed consent. Other vulnerable 
subjects include, for example, members of a group with a hierarchical structure 
such as university students, subordinate hospital and laboratory personnel, 
employees of the Sponsor, members of the armed forces, and persons kept in 
detention. 
 
 

 
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 Appendix III: Transthoracic Echocardiography Acquisition Guidelines 
Study endpoints will be determined with serial echocardiography performed at 
the individual study sites and interpreted at the Echocardiography Core 
Laboratory (ECL).  The independent ECL will be responsible for the review and 
assessment of all echocardiograms obtained on registered subjects.  The 
following guidelines should be followed for study echocardiograms.  
Echocardiographic analysis will be performed by the Echo Investigator.  All 
measures required by the eCRF should be completed or noted when not 
possible. 
I. 
General Echocardiographic Procedures 
1. The EKG signal should be clearly visible on all frames. 
2. Echocardiograms should be identified by the subject number assigned 
for the purpose of the trial.  The eCRF will identify subject number and 
the date of the visit. 
3. Echocardiographic data will be acquired and exported/transferred in 
digital format and saved as a DICOM image.   
4. Height will be measured at the time of the first echocardiogram and 
weight will be measured and recorded at the time of each 
echocardiogram.  
5. Blood pressure and heart rate will be recorded at the start of the echo 
study.  Diastolic and systolic pressures should be recorded on the echo 
study. 
6. Variance maps should be turned off for the study. 
7. An intravenous catheter may be placed for administration of left-sided 
contrast agent if needed for visualization of endocardial borders to 
enable accurate measurement of LV volumes.  If a contrast agent is 
used for the baseline echocardiogram, it should also be used for all 
subsequent follow-up echocardiograms. 
8. Site will provide a completed worksheet including clinical information to 
accompany the digital DICOM echocardiogram for each echo study.  For 
purposes of quality control, the site personnel are instructed to make and 

 
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record all of the measurements and calculations required on the 
worksheet for reference for each screening echo study. 
9. It is recommended that each site identify a single sonographer to 
perform all echo studies for a single subject, and that one 
echocardiography system be used for the image acquisition to the extent 
possible.   
 
II. 
Echocardiographic Protocol for Image Acquisition 
For the echocardiogram, the patient will be positioned in left lateral recumbency 
or in the position that permits optimal imaging.  It is strongly recommended that 
an echocardiography bed with a dropout be used if available.  With digital 
archiving, at least 3 cardiac cycles for normal sinus rhythm or paced, and at least 
5 cardiac cycles for Afib are requested.  Unless otherwise specified, depth should 
be adjusted to maximize the image while including all necessary structures.  All 
images will be acquired at end-expiration held during quiet respiration.  Harmonic 
imaging should be employed to optimize visualization of endocardial borders.  All 
spectral pulsed wave (PW) and continuous wave (CW) Doppler will be performed 
at a sweep speed of 100 mm/sec.  Color Doppler Nyquist limits will be adjusted 
to the range of 50 – 70 cm/sec, unless otherwise specified. 
1. PLAX with and without magnification of the left ventricular outflow tract; 
with and without color flow Doppler interrogation of the aortic and mitral 
valves.  Careful attention will be paid to identifying the vena contracta of 
the mitral regurgitant jet using zoom views.  The vena contracta is the 
narrowest portion (or the “neck”) of the jet as it crosses the valve leaflets.  
The Nyquist limit should be set between 50 and 70 cm/sec and a zone of 
proximal jet acceleration should be identified on the ventricular aspect of 
the leaflets. 
2. PSAX at the mid-papillary muscle level.  
3. PSAX at the tips of the mitral valve leaflets to identify the minimum 
diastolic orifice of the mitral valve. When a MitraClip implant is present 
each mitral valve orifice should be imaged separately. 
4. PSAX at the level of the mitral valve when both anterior and posterior 
leaflets are visualized.  Position the Color Doppler scan box over the 
mitral orifice to visualize the regurgitant jet origin. 

 
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5. Basal PSAX (at the aortic valve level).  Pulsed Doppler sample of 
pulmonary flow at the level of the pulmonary valve to measure 
pulmonary velocity time interval (VTI) opening and closing transients of 
the pulmonary valve should be recorded.  Optimization of the pulmonary 
valve annulus for measurement of the pulmonary annular diameter. 
6. Apical 4-chamber view, with and without color flow interrogation of mitral 
and tricuspid valves.  The color flow Doppler interrogation should include 
the entire left atrium taking care to include wall-impinging eccentric jets 
in the region of interest.  Gain should be adjusted to reduce excess 
noise.  Spectral Doppler interrogation in this view includes: 
a. PW Doppler of mitral inflow at mitral leaflet tips. 
b. PW Doppler of mitral inflow at the level of the mitral annulus at 
end-diastole with a small sample volume.  
c. CW of the mitral inflow signal. 
d. CW of the mitral regurgitant jet with care to record a complete 
signal and maximize the peak velocity.  Contrast should be used 
to enhance this signal when incomplete and when a peak 
velocity cannot be determined.  NOTE: Occasionally eccentric 
CW jets may require interrogation of additional views (EG. PLAX, 
Apical 2C view) to obtain the true maximal jet velocity. 
e. CW of tricuspid regurgitant jet for estimation of pulmonary artery 
systolic pressure.  If jet is inadequate for measurement, this 
recording should be repeated following contrast injection (see 
below). 
f. PW Doppler of right pulmonary vein flow.  The sample volume 
should be placed at least 1 cm within the pulmonary vein, if 
possible. If jet is inadequate for measurement, this recording 
should be repeated following contrast injection (see below). 
g. Color flow Doppler visualization of PISA (proximal isovelocity 
surface area) using zoomed views for estimation of regurgitant 
orifice area.  The Nyquist limit will be lowered and the baseline 
shifted in the direction of flow (toward left atrium) to maximize the 
PISA signal.  The PISA aliasing velocity should be set to 
optimize the hemispheric shape of the proximal flow 
convergence region (usually 30-40 cm). 

 
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7. Anteriorly angulated 4-chamber view: 
a. Color flow Doppler to exclude aortic insufficiency.  If present, 
aortic insufficiency jet will be optimized to permit measurement of 
the pressure half time using CW Doppler. 
b. PW Doppler in left ventricular outflow tract positioned such that 
closing artifact but not opening artifact of the valve is visible. 
c. CW Doppler through the aortic valve. 
8. Apical 2-chamber view with and without color interrogation of the mitral 
valve. 
9. Apical long-axis (also known as 3-chamber) view with and without color 
flow interrogation of the mitral valve.  Zoom mode should also be used to 
identify the vena contracta and PISA in this view, as noted above. 
10. Subcostal imaging of the inferior vena cava with and without a “sniff”. 
11. Color Doppler of inter-atrial septum to interrogate presence of ASD.   
12. Apical images of the left ventricle (LAX, 2- and 4-chamber views) should 
be collected taking care to minimize foreshortening.   
13. Contrast will be used for endocardial border delineation when the 
endocardium is not well visualized on the harmonic image.  For subjects 
with renal dysfunction, intravenous contrast should not be used during 
the procedure unless absolutely necessary.  Contrast can also be 
employed for enhancement of the tricuspid regurgitant and pulmonary 
venous flow signals.  During the contrast imaging, the mechanical index 
should be adjusted to avoid bubble destruction artifacts (usually a 
mechanical index of 0.3-0.5), and contrast infusion rate adjusted to avoid 
obliteration of the mitral annulus.  Ideally, the focus should be set at the 
mitral annulus level.  If a contrast agent is used for the baseline 
echocardiogram, it should also be used for all subsequent follow-up 
echocardiograms, unless subject experiences renal dysfunction. 
14. For follow-up post-MitraClip implant, images of the MitraClip(s) in the 
following four views should be collected both with and without color 
Doppler to verify MitraClip position: 
a. SAX – non-oblique at the Mitral Valve level 

 
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b. PLAX 
c. Apical 4-chamber and long-axis 
d. Anterior and posterior Intercomissural (IC) images 
 
Assessment of Mitral Regurgitation Severity  
 
For the purpose of assessing severity of mitral regurgitation by echocardiography 
pre- and post-procedure, mitral regurgitation severity will be determined based 
on the American Society of Echocardiography (ASE) Recommendations for 
Evaluation of The Severity of Native Valvular Regurgitation with Two-
Dimensional and Doppler Echocardiography.7         
 
The Echocardiography Core Laboratory will make all of the measurements 
required to determine the MR severity score using the integrative method based 
on qualitative and quantitative data as described in the ASE guidelines.  The 
table below outlines the guidelines used for determining MR severity grade. 
When two regurgitant jets are noted on the echocardiographic exam of a mitral 
valve after treatment (surgery or MitraClip), the jet with the greater regurgitation 
severity rating is recorded on the eCRFs.   
 
 
ASE Guidelines for MR Severity Scoring 
 
Variable 
Mild 
 
1+ 
Moderate 
 
2+ 
Moderate to 
Severe 
3+ 
Severe 
 
4+ 
Color Flow Jet Small (<4 cm2 
or <10% of LA 
area) and 
central 
Central, 
moderate  
(4 - 6 cm2 or 10-
30% of LA area) 
Central, large 
(>6 < 8 cm2 or 
>30%<40% of 
LA area) or 
Eccentric 
reaching 1st PV 
Central, large 
(≥8 cm2 or 
≥40% of LA 
area) or 
Eccentric 
reaching 2nd PV 
Pulmonary 
Vein Flow 
Systolic 
dominant 
Diastolic 
dominant 
All diastolic 
Systolic flow 
reversal 
Regurgitant 
Volume 
(mL/beat) 
 
< 30 
 
30 - 44 
 
45 – 59 
 
≥60 

 
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Variable 
Mild 
 
1+ 
Moderate 
 
2+ 
Moderate to 
Severe 
3+ 
Severe 
 
4+ 
Regurgitant 
Fraction (%) 
 
< 30 
 
30 - 39 
 
40 -49 
 
≥50 
EROA (cm2)  
< 0.20 
0.20-0.29 
0.30-0.39 
≥ 0.40 
Vena 
contracta 
width  
< 0.5 cm 
≥0.5 cm 
 
 
 

 
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 Appendix IV: Revision History 
Amendment 
Number 
Version 
Date 
Details 
Rationale 
NA 
A 
03SEP2020 
First Release 
NA 
1 
B 
03DEC2020 1. Changed sponsor name 
from Abbott to Abbott 
Vascular. 
2. Change NMPA Order No 
25 to NMPA applicable 
regulations. 
 
3. Changed “BUN” to “urea”. 
 
 
4. Added BNP and NT 
proBNP tests. 
 
 
 
5. Changed “enrolled” to 
“registered” when referring 
to subjects.  
1. To align with 
approval notice. 
 
2. NMPA Order No 25 
not applicable for 
PMS.  
 
3. Blood urea is more 
commonly used. 
 
4. Both parameters are 
commonly used in 
the current MitraClip 
trials. 
 
5. Per protocol 
definitions.  
 
 
 

 
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 Appendix V: Protocol Summary 
Trial Name and 
Number 
MitraClip China PMS 
CRD956-PMS 
Title 
MitraClip China PMS: A Prospective, Multi-Center, Single-Arm, Post 
Market Study of the MitraClip System for the Treatment of Symptomatic 
Mitral Regurgitation in China (CRD956-PMS) 
Objectives 
To confirm the evidence of safety and efficacy of MitraClip system in 
Chinese subjects with a post market setting.  
Devices 
MitraClip System (CDS0601-NTR, CDS0601-XTR, SGC0301)  
 
Targeted number of 
subjects to receive 
study device 
A minimum of 50 subjects and a maximum of approximately 100 
subjects at up to 10 sites in China.   
Study Design 
• 
Prospective, multi-center, single-arm, post market study  
• 
Subjects will be evaluated at baseline, index procedure, discharge, 
30 days and 1 year 
Primary Endpoints 
• 
Acute Procedural Success (APS) 
• 
Freedom from Major Adverse Event (MAE) rate at 30 days 
Descriptive 
Endpoints 
Clinical Endpoints:  
 
The following descriptive clinical endpoints will be assessed at all 
scheduled office visits. 
• 
All-cause mortality  
• 
Freedom from the components of MAE  
• 
NYHA Functional Class  
• 
Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of 
Life (QoL) scores  
• 
Six Minute Walk Test (6MWT) distance  
• 
Mitral valve surgery (including type of surgery), including reason 
for intervention  
• 
Additional MitraClip System intervention, including reason for 
intervention  
• 
Number of hospitalizations and reason for hospitalization (i.e. 
heart failure, cardiovascular, non-cardiovascular) in study period 
• 
Device-related complications: defined as a composite of single 
leaflet device attachment (SLDA), device embolization, clinically 
significant iatrogenic septal defect or mitral stenosis that requires 
intervention 
• 
Major bleeding  

 
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Device and Procedure-Related Endpoints:  
 
• 
Implant Success Rate: Defined as the rate of successful delivery 
and deployment of one or more MitraClip devices and retrieval of 
the delivery catheter 
• 
Device Procedure Time: Defined as the time elapsed from the 
start of the transseptal procedure to the time the Steerable Guide 
Catheter is removed 
• 
Total Procedure Time: defined as the time elapsed from the first of 
any of the following: intravascular catheter placement, anesthesia 
or sedation, or transesophageal echocardiogram (TEE), to the 
removal of the last catheter and TEE 
• 
Device Time: Defined as the time the Steerable Guide Catheter is 
placed in the intra-atrial septum until the time the MitraClip 
Delivery System (CDS) is retracted into the Steerable Guide 
Catheter 
• 
Fluoroscopy Time: defined as the total minutes of exposure to 
fluoroscopy during the MitraClip procedure 
• 
Length of stay in Intensive Care Unit/Critical Care Unit/Post-
Anesthesia Care Unit (ICU/CCU/PACU)  
• 
Length of hospital stay for index MitraClip procedure 
 
Echocardiographic Endpoints:  
 
The following descriptive echocardiographic endpoints will be 
assessed at all scheduled office visits. 
• 
MR Severity Grade 
• 
Effective Regurgitant Orifice Area 
• 
Regurgitant Volume (RV) 
• 
Regurgitant Fraction (RF) 
• 
Left Ventricular End Diastolic Volume (LVEDV) 
• 
Left Ventricular End Systolic Volume (LVESV) 
• 
Left Ventricular End Diastolic Dimension (LVEDD) 
• 
Left Ventricular End Systolic Dimension (LVESD) 
• 
Left Ventricular Ejection Fraction (LVEF) 
• 
Right Ventricular Systolic Pressure (RVSP) 
• 
Mitral Valve Area (MVA) 
• 
Mean Mitral Valve Pressure Gradient (MVG) 
• 
Systolic Anterior Motion of the mitral valve (present or absent) 
• 
Forward Stroke Volume (FSV) 
• 
Cardiac Output (CO) 
• 
Cardiac Index (CI) 
Subject Follow-up 
Subjects will have scheduled office visit evaluations for assessment of 
study endpoints at hospital discharge, 30 days and 1 year. 

 
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Inclusion Criteria 
• 
Subject is eligible to receive the MitraClip per the current 
approved MitraClip System IFU  
• 
Subject is 18-year-old or above  
• 
Subject who gives consent for study procedure 
Exclusion Criteria 
• 
Subject cannot tolerate procedural anticoagulation or anti-platelet 
regimen 
• 
Subject with active endocarditis of mitral valve 
• 
Subject with rheumatic mitral valve disease 
• 
Subject with echocardiographic evidence of intracardiac, IVC or 
femoral venous thrombus  
• 
Subject is unlikely to survive the protocol follow up period of 12-
months after device implant 
• 
Subject has insufficient or lost ability to maintain their will and 
rights 
• 
Subject is illiterate 
• 
Subject participates in another clinical study that may impact the 
follow-up or results of this study 
 
 

 
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 Appendix VI: References 
 
1Zhou Daxin, Pan Wenzhi, Guan Lihua, Ge Junbo. Mid-term follow-up report of 
three cases treated with MitraClip for Mitral Regurgitation. Chinese Journal of 
Interventional Cardiology. 2013; 21:240–243. 
 
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