A Prospective, 1: 1 Randomized, Single Blind, Multi-center Human Clinical Trial
Phase: NA
Conditions: Pathological Fracture of Vertebra Due to Secondary Osteoporosis (Disorder), Pathological Fracture of Vertebra Due to Neoplastic Disease (Disorder)
Sponsor: Medtronic Spinal and Biologics

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  
Xpede Clinical study 
Study Product Name 
Kyphon®XpedeTMBone Cement 
Model/Specification 
CX01A 
Category of investigational medical device 
Class III  
Similar product in China 
Yes 
Class III medical devices requiring clinical trial 
approval: 
No 
Sponsor:  
Medtronic SOFAMOR DANEK USA 
1800 Pyramid Place, Memphis, TN USA 38132. 
Local Sponsor 
Medtronic (Shanghai) Management Co., Ltd. 
11F, Building B, No 5, Lane 255, DongYu Road, 
Pudong, Shanghai 
Document Version 
Version 3 17 Sep 2018 
Coordinating Investigator 
Prof. Yang Huilin 
Clinical trial  institution 
The First Affiliated Hospital of Soochow 
University 
188 Shizi Street, Soochow, China 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it 
is confidential and that it may not be further disclosed by them. 
 
 

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1. Investigator Statement and Institution Statement 
 
Study Title 
Xpede Study 
Study product Name 
Kyphon®XpedeTMBone Cement 
Sponsor:  
Medtronic SOFAMOR DANEK USA 
1800 Pyramid Place, Memphis, TN USA 38132. 
Local Sponsor 
Medtronic (Shanghai) Management Co., Ltd. 
11F, Building B, No 5, Lane 255, DongYu Road, Pudong, 
Shanghai 
Clinical Investigation Plan Identifier 
NA 
Version Number/Date  
Version 3  17 Sep 2018 
1. I will conduct this clinical trial in strict compliance with the Declaration of Helsinki, current laws 
and regulations of China, and the requirements of the protocol; 
2. And record all required data accurately on the Case Report Form (CRF) and complete the final 
report of the clinical trial on time; 
3. The investigational medical device will be used only for this clinical trial and the receipt and use 
of the investigational medical device will be recorded completely and accurately and the records 
will be retained during the process of the clinical trial; 
4. The monitor and verifier authorized or designated by the Sponsor and the regulatory 
authorities are allowed to conduct monitoring, verification and inspection for the clinical trial; 
5.The clinical trial should be conducted in strict compliance with contract/articles of agreement 
signed by all parties. 
I have already read the clinical study protocol, including the above statement and I fully agree all 
the above requirements. 
 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Date: 
 
Institution: 
 
 
 
 

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Read and Approved by Clinical Research Institution  
 
Study Title 
Xpede Study 
Study product Name 
Kyphon®XpedeTMBone Cement 
Sponsor:  
Medtronic SOFAMOR DANEK USA 
1800 Pyramid Place, Memphis, TN USA 38132. 
Local Sponsor 
Medtronic (Shanghai) Management Co., Ltd. 
11F, Building B, No 5, Lane 255, DongYu Road, Pudong, 
Shanghai 
Version Number/Date  
Version 3 17 Sep 2018 
 
 
    
 
____________________________________________ 
Site Name 
 
 
____________________________________________ 
Comments of Clinical Research Institution 
 
 
____________________________________________        
Signature/ Stamp 
 
 
____________________________________________ 
Date (dd/mmm/yyyy) 
 
 

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Table of Contents  
 
1. 
Investigator Statement and Institution Statement .................................................................... 2 
Read and Approved by Clinical Research Institution ............................................................................. 3 
Table of Contents ......................................................................................................................... 4 
List of Tables ............................................................................................................................... 8 
2. 
Glossary ............................................................................................................................... 8 
3. 
Synopsis ............................................................................................................................ 15 
4. 
Introduction ....................................................................................................................... 19 
4.1. Background ........................................................................................................................... 19 
4.2. Purpose ................................................................................................................................ 20 
5. 
Objectives and Endpoints ..................................................................................................... 22 
5.1. Objectives ............................................................................................................................. 22 
5.1.1. 
Primary Objective(s)............................................................................................................ 22 
5.1.2. 
Secondary Objective(s) ...................................................................................................... 22 
5.2. Endpoints .............................................................................................................................. 22 
5.2.1. 
Primary Endpoint(s) ............................................................................................................. 22 
5.2.2. 
Secondary Endpoints(s) ...................................................................................................... 22 
6. 
Study Design ...................................................................................................................... 23 
6.1. Duration ................................................................................................................................ 23 
6.2. Rationale ............................................................................................................................... 23 
7. 
Product Description ............................................................................................................. 24 
7.1. General ................................................................................................................................. 24 
7.2. Manufacturer ......................................................................................................................... 25 
7.3. Packaging .............................................................................................................................. 25 
7.4. Intended Population ............................................................................................................... 25 
7.5. Contraindications ................................................................................................................... 25 
7.6. Product Use ........................................................................................................................... 26 
7.7. Product Receipt and Tracking .................................................................................................. 30 
7.8. Product Storage ..................................................................................................................... 30 

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7.9. Product Return ...................................................................................................................... 31 
7.10. Product Accountability ........................................................................................................... 31 
8. 
Selection of Subjects ........................................................................................................... 31 
8.1. Study Population .................................................................................................................... 31 
8.2. Subject Enrollment ................................................................................................................. 31 
8.3. Inclusion Criteria .................................................................................................................... 32 
8.4. Exclusion Criteria ................................................................................................................... 32 
9. 
Study Procedures ................................................................................................................ 33 
9.1. Schedule of Events ................................................................................................................. 33 
9.2. Subject Consent .................................................................................................................... 34 
9.3. Stratification and Treatment Assignment ................................................................................. 36 
9.4. Baseline ................................................................................................................................ 36 
9.5. Prior and Concomitant Medications .......................................................................................... 37 
9.6. Procedure day ........................................................................................................................ 37 
9.7. Follow up visits ....................................................................................................................... 38 
9.8. Radiography assessment ........................................................................................................ 38 
9.9. Assessment of Efficacy ........................................................................................................... 41 
9.10. Assessment of Safety ............................................................................................................. 42 
9.11. Recording Data ...................................................................................................................... 42 
9.12. Deviation Handling ................................................................................................................. 43 
9.13. Subject Withdrawal or Discontinuation ..................................................................................... 44 
10. 
Risks and Benefits ............................................................................................................. 45 
10.1. Potential Risks ....................................................................................................................... 45 
10.2. Potential Benefits ................................................................................................................... 46 
10.3. Risk-Benefit Rationale............................................................................................................. 46 
10.4. Probability analysis of success ................................................................................................. 47 
10.5. Probability analysis of failure .................................................................................................... 47 
11. 
Adverse Events and Device Deficiencies .............................................................................. 47 
11.1. Definitions/Classifications ...................................................................................................... 47 
Adverse Event Relationship Classification ........................................................................................ 49 
11.1.1. 
Subject Death................................................................................................................... 52 

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11.2. Reporting of Adverse Events and Device deficiencies ................................................................. 52 
11.3. Emergency contact details ...................................................................................................... 53 
12. 
Statistical Design and Methods .......................................................................................... 55 
13. 
Sample size determination ................................................................................................. 56 
13.1. Primary Objective #1 (Efficacy) ................................................................................................ 56 
13.1.1. 
Background .................................................................................................................. 56 
13.1.2. 
Sample Size Calculations ................................................................................................ 56 
13.2. Primary Objective #2 (Efficacy) ................................................................................................ 57 
13.2.1. 
Background .................................................................................................................. 57 
13.2.2. 
Sample Size Calculations ................................................................................................ 58 
13.3. 
Data analysis and reporting ............................................................................................ 59 
13.4. 
Analysis of Clinical Data ................................................................................................. 59 
14. 
Ethics .............................................................................................................................. 61 
14.1. 
Statement(s) of Compliance ........................................................................................... 61 
14.2. 
Ethics Committee (EC) ................................................................................................... 62 
14.2.1. 
General Study Requirements .......................................................................................... 62 
14.2.2. 
Informed Consent and Ethics Committees ....................................................................... 63 
14.3. 
Monitoring .................................................................................................................... 63 
14.4. 
Data Management ......................................................................................................... 64 
14.5. 
Direct Access to Source Data/Documents ........................................................................ 65 
15. 
Study Administration ........................................................................................................ 65 
15.1. 
Confidentiality .............................................................................................................. 65 
15.2. 
Liability ........................................................................................................................ 66 
15.3. 
Finance ......................................................................................................................... 66 
15.4. 
CIP Amendments ........................................................................................................... 66 
15.5. 
Responsibilities of all Parties ........................................................................................... 66 
15.6. 
Record Retention ........................................................................................................... 67 
15.6.1. 
Investigator Records ..................................................................................................... 67 
15.6.2. 
Investigator Reports ...................................................................................................... 67 
15.6.3. 
Medtronic Records ........................................................................................................ 70 
15.6.4. 
Medtronic Reports ........................................................................................................ 71 

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15.7. 
Publication and Use of Information .................................................................................. 72 
15.8. 
Suspension or Early Termination ..................................................................................... 73 
15.8.1. 
Planned Study Closure ................................................................................................... 73 
15.8.2. 
Early Termination or Suspension ..................................................................................... 73 
15.8.3. 
Procedures for Suspension or Termination ...................................................................... 74 
16. 
Appendixes ...................................................................................................................... 76 
Version History .......................................................................................................................... 78 
 
 
 

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List of Tables  
Table 1: Products information ................................................................................................................. 24 
Table 2: Products Characteristics ........................................................................................................... 24 
Table 3: Dough time, hardening time and working period informations .............................................. 26 
Table 4: Handling Characteristics of KYPHON®  Xpede™ Bone Cement at 23 ± 1°C ........................ 27 
Table 5: Schedule of Events ..................................................................................................................... 33 
Table 6: Adverse Event Definitions ......................................................................................................... 47 
Table 7: Unavoidable Adverse Events ..................................................................................................... 51 
Table 9: Investigator Reports per Medtronic Requirements ................................................................ 68 
Table 10: Sponsor Reports ....................................................................................................................... 71 
2. Glossary 
 
Term 
Definition 
Adverse Event 
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 investigational medical 
device.  
NOTE 1: This definition includes events related 
to the investigational medical device or the 
comparator. 
NOTE 2: This definition includes events related 
to the procedures involved. 
NOTE 3: For users or other persons, this 
definition is restricted to events related to 
investigational medical devices. 
(ISO 14155:2011 section 3.2) 
_________________________________________ 
The 
medical 
events 
with 
disadvantages 
occurred during the clinical study, no matter 
whether they are related to investigational 
medical devices or not. 
(CFDA Order No. 25 Article 93) 
 
Adverse Device Effect (ADE) 
Adverse event related to the use of an 
investigational medical device. 

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Term 
Definition 
NOTE 1: This definition includes adverse events 
resulting from insufficient or inadequate 
instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of 
the investigational medical device. 
NOTE 2: This definition includes any event 
resulting from use error or from intentional 
misuse of the investigational medical device. 
(ISO 14155:2011 section 3.1) 
Audit 
Systematic 
independent 
examination 
of 
activities and documents related to clinical 
investigation to determine whether these 
activities were conducted, and the data 
recorded, analyzed and accurately reported, 
according to the CIP, standard operating 
procedures, this International Standard and 
applicable regulatory requirements. 
Case Report Forms (CRFs) 
A paper or electronic data collection form, 
designed to collect information on each subject 
as required by the Study Protocol / Clinical 
Investigation Plan. 
Charter 
Document that describes the committee 
membership, roles and responsibilities, and 
processes to be utilized by the committee. 
Clinical Data 
Any data collected in a clinical study and stored 
in a study database or related database, 
including device databases and clinical study 
records (e.g., subject questionnaires, discharge 
summaries, save-to-disk and informed consent 
documents). 
Clinical Database  
 
The compilation of data fields that store the 
data collected for a study.  
Clinical Investigation Plan (CIP) 
Document 
that 
state(s) 
the 
rationale, 
objectives, design and proposed analysis, 
methodology, monitoring, conduct and record-
keeping of the clinical investigation. 
Note: The term “protocol” is synonymous with 
“CIP”. However, protocol has many different 
meanings, 
some 
not 
related 
to 
clinical 
investigation, and these can differ from country 
to country. Therefore, the term CIP is used in 
this International Standard. 

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Term 
Definition 
Clinical Study Report (CSR) 
A written description of a study of any 
therapeutic, prophylactic, or diagnostic agent 
conducted in human subjects, in which the 
clinical 
and 
statistical 
description, 
presentations, and analyses are fully integrated 
into a single report. 
Clinical Study Synopsis 
An outline of the general requirements and 
parameters of the study. The synopsis is used as 
a tool in developing the protocol as well as 
providing insight as to what resources may be 
required to conduct the study. 
Close-out Visit (COV) 
A final monitoring visit to a site conducted to 
obtain all required study-related information, 
and to review ongoing and future study-related 
investigator responsibilities (e.g., regulatory 
inspector access, document archival, financial 
disclosure) per contractual agreements and 
relevant regulations. 
Compliance (in relation to studies) 
Adherence 
to 
all 
the 
study-related 
requirements, good clinical practice (GCP) 
requirements, and the applicable regulatory 
requirements.  
Consent Form 
See Informed Consent. 
Ethics Committee (EC) 
Independent body whose responsibility is to 
review clinical investigations in order to protect 
the rights, safety and well-being of human 
subjects participating in a clinical investigation. 
Also known as the Institutional Review Board 
(IRB). 
Note: For the purposes of this International 
Standard, “ethics committee” is synonymous 
with 
“research 
ethics 
committee,” 
“independent 
ethics 
committee” 
or 
“institutional review board”. The regulatory 
requirements pertaining to ethics committees 
or similar institutions vary by country or region. 
Good Clinical Practice (GCP) 
A 
standard 
for 
the 
design, 
conduct, 
performance, monitoring, auditing, recording, 
analyses, and reporting of clinical studies that 
provides assurance that the data and reported 
results are credible and accurate, and that the 

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Term 
Definition 
rights, integrity, and confidentiality of study 
subjects are protected. 
Inclusion/ Exclusion Criteria 
The medical or social standards determining 
whether a person may or may not be allowed to 
enter a clinical study. These criteria are based on 
such factors as age, gender, the type and stage 
of a disease, previous treatment history, and 
other medical conditions. The criteria are not 
used to reject people personally, but to identify 
appropriate participants and keep them safe. 
Independent  
Not involved in the conduct of a clinical 
investigation, except for their specifically 
assigned responsibilities, in order to avoid bias 
or a conflict of interest. 
Informed Consent 
A process by which a subject voluntarily 
confirms his or her willingness to participate in a 
particular study, after having been informed of 
all aspects of the study that are relevant to the 
subject’s decision to participate. Informed 
consent is documented by means of a written, 
signed and dated informed consent form. 
Inspection 
The act by a regulatory authority(ies) of 
conducting an official review of documents, 
facilities, records, and other resources that are 
deemed by the authority(ies) to be related to 
the clinical study and that may be located at the 
site of the study, at the sponsor’s and/or 
contract 
research 
organization’s 
(CROs) 
facilities, or at other establishments deemed 
appropriate by the regulatory authority(ies). 
Institution 
A person, other than an individual, who engages 
in the conduct of research on subjects or in the 
delivery of medical services to individuals as a 
primary activity or as an adjunct to providing 
residential or custodial care to humans. The 
term 
includes, 
for 
example, 
a 
hospital, 
retirement 
home, 
confinement 
facility, 
academic 
establishment, 
and 
device 
manufacturer. 
Institutional Review Board (IRB) 
Any board, committee, or other group formally 
designated by an institution to review, to 
approve the initiation of, and to conduct 

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Term 
Definition 
periodic 
review 
of, 
biomedical 
research 
involving human subjects. The primary purpose 
of such review is to assure the protection of the 
rights and welfare of the human subjects. Also 
known as Ethics Committee (EC). 
Interim Monitoring Visit (IMV) 
A site visit conducted during the execution 
phase of a clinical study to assure the 
Investigator’s 
obligations 
to 
the 
study 
protocol/CIP are being fulfilled and the facilities 
used in the clinical study continue to be 
acceptable.  
Investigational Device 
A device, including a transitional device, which is 
the object of an investigation. 
Investigational Site  
Institution 
or 
site 
where 
the 
clinical 
investigation is carried out.  
Investigational Product  
A product (e.g., Device, Drug, Software) that is 
being evaluated in a clinical study and;  
- is not approved/cleared, or  
- is different from the approved/cleared form, 
or  
- is being used for an unapproved or uncleared 
indication/use.  
Investigator  
A person responsible for the conduct of the 
clinical study at the study site. If a study is 
conducted by a team of individuals at a study 
site, the investigator is the responsible leader of 
the team and may be called the principal 
investigator. See also Sub- 
Investigator.  
Investigator’s Brochure (IB)  
A compilation of the clinical and nonclinical data 
on the study product(s) that is relevant to the 
study of the study product(s) in human subjects.  
Investigator Site File (ISF)  
A study-specific file maintained by the Principal 
Clinical 
Investigator, 
which 
contains 
all 
documentation specific to their clinical site. 
Also called a Site Regulatory Binder.  
Monitoring 
Act of overseeing the progress of a clinical 
investigation and to ensure that it is conducted, 
recorded, and reported in accordance with the 
CIP, written procedures and the applicable 
regulatory requirements. 

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Term 
Definition 
Monitoring Visit 
A visit to a clinical study site by a qualified 
monitor for the purpose of performing a site 
qualification visit (SQV), site initiation visit (SIV), 
interim monitoring visit (IMV) or close out visit 
(COV) activities. 
Protocol 
See Clinical Investigation Plan. 
Protocol Amendment 
A written description of a change(s) to or formal 
clarification of a protocol. 
Publication 
A medical or scientific written or electronic 
summary of research work that is used to 
educate external audiences, such as HCPs, on 
the use(s) or benefit(s) of Medtronic products 
and therapies. 
Publication Plan 
The specific tasks and deliverables in order to 
execute on the publications strategy. 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of 
the consequences characteristic of a serious 
adverse event. 
Serious Adverse Event (SAE) 
 See definition in the Table 6 for SAE. 
Site Initiation Visit (SIV) 
A site visit designed to document general site 
readiness, including but not limited to, a review 
of study procedures and the Investigator’s 
responsibilities with the investigator and site 
personnel. 
Site Initiation 
The process of gathering regulatory documents 
and conducting the activities required to 
activate a site to enroll subjects in a clinical 
study. The initiation process begins after the 
site is selected to participate in the clinical 
study. 
Source Data 
All information in original records and certified 
copies of original records of clinical findings, 
observations, or other activities in a clinical 
study necessary for the reconstruction and 
evaluation of the clinical study. Source data are 
contained 
in 
source 
documents 
(original 
records or certified copies). 
Source Documents /Documentation  
Original documents, data, and records (e.g., 
hospital records, clinical and office charts, 
laboratory notes, memoranda, subject’s diaries 

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Term 
Definition 
or evaluation checklists, pharmacy dispensing 
records, 
recorded 
data 
from 
automated 
instruments, copies or transcriptions certified 
after verification as being accurate and 
complete, 
microfiches, 
photographic 
negatives, microfilm or magnetic media, x-rays, 
subject files, and records kept at the pharmacy, 
at the laboratories, and at medico-technical 
departments involved in the clinical study).  
Sponsor 
An 
individual, 
company, 
institution, 
or 
organization that takes responsibility for the 
initiation, management, and/or financing of a 
clinical study. 
Study Deviation 
An event where the clinical investigator or site 
personnel did not conduct protocol required 
procedures according to the study protocol. 
Sub-Investigator (Sub-I) 
Any individual member of the clinical study team 
designated and supervised by the investigator 
at a study site to perform critical study-related 
procedures and/or to make important study-
related decisions (e.g., associates, residents, 
research fellows). See also Investigator. 
Subject/Study Subject 
An individual who participates in a clinical study 
either as a recipient of the study product(s) or as 
a control. 
Suspension (study or site) 
A temporary postponement of study activities 
related to enrollment and distribution of the 
product. (Possible for the total study or a single 
site.) 
Termination (study or site) 
Discontinuance, by sponsor or by withdrawal of 
EC or NMPA  approval, of an investigation before 
completion. 
Termination Letter 
A letter terminating an agreement or contract. 
 
 

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3. Synopsis 
 
Title 
Xpede Study 
Clinical Study Type 
The Xpede Study is a prospective, 1: 1 randomized, single blind, 
multi-center human clinical trial. 
Product Name 
Kyphon®Xpede™ Bone Cement 
Class of the product 
III 
Similar Product in China 
Yes 
Sponsor:  
Medtronic SOFAMOR DANEK USA 
1800 Pyramid Place, Memphis, TN USA 38132. 
Local Sponsor 
Medtronic (Shanghai) Management Co., Ltd. 
11F, Building B, No 5, Lane 255, DongYu Road, Pudong, Shanghai 
Phone: +86 21 2032 5239  
Indication 
under 
investigation  
KYPHON™ Xpede™ Bone Cement is indicated for the treatment of 
pathological fractures of the vertebral body due to osteoporosis, 
cancer, or benign lesions using a cementoplasty (i.e. kyphoplasty or 
vertebroplasty) procedure. It is also indicated for the fixation of 
pathological fractures of the sacral vertebral body or ala using sacral 
vertebroplasty or sacroplasty. Cancer includes multiple myeloma and 
metastatic lesions, including those arising from breast or lung cancer, 
or lymphoma. Benign lesions include hemangioma and giant cell 
tumor. 
Pathological 
fracture 
may 
include 
a 
symptomatic 
microfracture (as documented by appropriate imaging and/or 
presence of a lytic lesion) without obvious loss of vertebral body 
height. 
Investigation Contents 
Medtronic (Shanghai) Management Co., Ltd is sponsoring the Xpede 
study for product registration in China. This study is a prospective, 
randomized, single-blinded, multi-site study conducted in mainland 
China. The study is considered an investigational trial in China. The 
purpose of the XPEDE study is to demonstrate that Kyphon® 
Xpede™ Bone Cement is non-inferior to the Mendec Spine Bone 
Cement in terms of safety and efficacy. A total of 180 patients will be 
enrolled over a period of 6 months and followed for 6 months after 
the procedure.  
Product Status 
Kyphon®Xpede™ Bone Cement: 
CE mark was obtained in May 2014; 
FDA approval was obtained in 2011. 
Investigational status in China 
Primary Objective(s) 
The primary objective is to demonstrate that: 
•the mean change of NRS score from baseline assessed at 6 months 
post operation  in the subjects treated with Kyphon®Xpede™ Bone 

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Cement is non-inferior to that in the subjects treated with Mendec 
Spine Bone Cement;  
•Change in Vertebral Body Angles from baseline at 6 months in the 
subjects treated with Kyphon®Xpede™ Bone Cement is non-inferior 
to that in the subjects treated with Mendec Spine Bone Cement 
Secondary Objective(s) 
Secondary objective is to evaluate the secondary endpoints 
including: 
Change of NRS score from baseline at 1 day and 3 months 
Change of ODI from baseline at 1 day, 3-month visit and 6-month 
visit. 
Change of SF-36 from baseline at 1 day, 3-month visit and 6-month 
visit 
Change in Vertebral body height restoration at 1 day and  3-month 
visit and 6 month 
Change in Vertebral Body Angles from baseline at 1 day, 3-month 
visit  
Adverse events through 6-month visit. 
Study Design 
This is a single blinded, randomized, multicenter study. 
Target population are patients who are diagnosed with pathological 
vertebral body fracture and will undergo BKP or VP procedures. 
180 patients will be randomized to receive either Kyphon®Xpede™ 
Bone Cement or Mendec. Timeframe for patient visit includes V1 
(pre-operative), V2 (operative), V3 (1d), V4 (3 months), V5 (6 months). 
Randomization 
180 patients will be randomized into 2 groups in a 1:1 ratio. Permuted 
block randomization stratified by site, the number of levels to be 
treated and the type of procedure (VP versus BKP) will be used. 
Sample Size 
180 patients will be enrolled and randomized 
Inclusion/Exclusion 
Criteria 
Subjects will be included if ALL of the following inclusion criteria are 
met: 
1) Subject being diagnosed as having painful pathological vertebral 
body fracture, who is suitable for VP/BKP procedure (1-3 levels) 
according to clinic practice. 
2) Subjects who are willing to participate in study through consent 
and willing to undergo study specific required procedures with 
expectancy of geographically stable for follow up duration. 
3) Subjects are at least 18  and ≤80 years old . 
 
Subjects will be excluded if ANY of the following exclusion criteria is 
met: 
1) Subject has a local or systemic infection 
2) Subject has pains caused by other spine disease than painful 
pathological vertebral compression fracture 
3) Subject has a medical condition with less than 1 year of life 
expectancy 

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4) Subject is grossly obese, i.e. BMI≥40 
5) Subject has medical conditions that represent contraindications 
for the use of bone cement by investigator’s decision 
6) Subject has an allergy or an intolerance to bone cement 
component 
7) Subject has past spinal surgeries at the target level(s) for which the 
VP/BKP procedure is suitable.  
8) Subjects who are currently enrolled or planning to participate in a 
potentially confounding drug or device trial during the course of this 
study.  Co-enrollment in concurrent trials is only allowed when 
document pre-approval is obtained from the Medtronic study 
manager and Medtronic Medical Advisor. 
9) Pregnant women or breastfeeding women, or women of child 
bearing potential who are not on a reliable form of birth regulation 
method or abstinence. 
10)Subjects with exclusion criteria required by local law (age or 
other). 
11)Subjects with medical condition which precludes them from 
participation in the opinion of the Investigator 
 
Study Procedures and 
Assessments 
Data collection is performed at baseline (pre-operative – V1), during 
the procedure (V2), 1 day post-operative (V3),3 months (V4) and 6 
months (V5) post procedure.  
Safety Assessments 
Adverse Events will be recorded and reported according to local 
regulatory requirements. It is the responsibility of the Investigator to 
abide by the adverse event reporting requirements stipulated by 
local law and the sites’ Ethics Committee. 
 Statistics 
This is a non-inferiority study. Since there are two primary efficacy 
endpoints, the overall sample size will be determined by the primary 
objective that requires the larger sample size. The non-inferiority 
hypothesis on the NRS requires 180 subjects (attrition: 15%) by 1:1 
randomization schedule. Since the sample size on Angulation lead to 
200 levels, and therefore to 148 subjects (attrition: 20%), the sample 
size will be 180 subjects. The study is considered as a success if both 
primary objectives are met.  
The data will be primarily analyzed according to the intention-to-
treat principle and a Full Analysis Set will be used for primary final 
analysis. 
The analysis on the first primary endpoint based on NRS will use one 
measure per patient and the comparison will be between the average 
NRS in both groups. It will be claimed that XPEDE is not inferior to 
MENDEC with respect to NRS score if the upper bound of the two-

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sided 95% confidence interval of the difference (µX(t) -µM(t)) is less 
than the margin. 
The analysis on the second primary endpoint based on Index 
Vertebral Body Angles will use multiple data points per patient 
according to the number of levels treated. The analysis will be 
performed by means of Generalized Estimating Equation (or mixed 
models for repeated measures) using patient as the subject.  
The analyses based on freedom from event at 6 months will be 
described by means of Kaplan-Meier curves. Cox models will be fitted 
and hazard ratios (HRs) with 95% confidence intervals will be 
computed.  
The rate of event will be computed and reported separately for each 
group, together with their 95% confidence intervals. Rates were 
compared by means of either a mixed Poisson model or a negative 
binomial regression model (if over dispersion was present). Incident 
rate ratios (IRRs) and 95% confidence intervals were used to compare 
the two groups. 
Analysis of endpoints based on comparisons between groups on 
continuous measurements will be performed by Student’s t-test or 
non-parametric test (Mann–Whitney U test) for normal and non-
normal distributions, respectively. Categorical variable parameter 
comparisons will be performed using a Chi-square test, or a Mantel-
Haenszel test for trend for ordinal variables with 3 or more 
categories.  
List of all clinical trial 
institutions 
and 
investigators 
for 
multicenter clinical trial 
Name 
of 
clinical trial 
institution 
Investigator Title 
Contact information 
The 
First 
Affiliated 
Hospital 
of 
Soochow 
University 
 
Prof. 
Yang 
Huilin 
Professor 
188 
Shizi 
Street, 
Soochow, China 
The 
First 
Affiliated 
Hospital 
of 
Zhengzhou 
University 
Prof. 
Liu 
Hongjian 
Professor 
No. 1 East Jianshe Road, 
Zhengzhou 
 
Hunan 
Provincial 
Prof. 
Liu 
Xiangyang 
Professor 
No. 61 West Jiefang 
Road, Changsha 

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People’s 
Hospital 
4. Introduction  
4.1. 
Background  
With the aging population, vertebral compression fracture (VCF) is nowadays representing a major 
issue in the health management of elderlies. VCFs can result as a consequence of osteoporosis but 
also malignant and benign tumors1 . Percutaneous vertebroplasty (VP) and percutaneous balloon 
kyphoplasty (BKP) are two minimally invasive widely used vertebral augmentation procedures to 
stabilize vertebral body fractures and alleviate pain 2. In both procedures, under fluoroscopy bone 
cement is injected into the vertebral body with a transpedicular approach.    
During percutaneous vertebroplasty, a small needle is inserted percutaneous!y into the vertebral 
body through the pedicles. PMMA based bone cement is injected into the cancellous bone of the 
vertebral body. The bone cement fills the bony trabeculae to stabilize the bone.  
During BKP, an Inflatable Bone Tamp (IBT) is inserted through the cannula into the vertebral body. 
Inflation of the IBT results in a restoration of vertebral body anatomy, with height restoration and 
angular deformity correction. IBT inflation is controlled by a pressure-measuring device; inflation of 
the IBT with radiopaque contrast material is visualized on intraoperative fluoroscopy. The IBT also 
compacts cancellous bone, which may help to provide stabilization. Void creation through 
cancellous bone compaction also reduces the potential for the fixation material to go beyond the 
region of its intended application. ' The IBT is removed, and the void created by the IBT is filled with 
viscous PMMA-based bone cement using a Bone Filler Device (BFD). 
Polymethylmethacrylate (PMMA) has been used as biomaterial in orthopedic surgeries since the late 
1960s. A large literature supports the use of bone cement as a bone void filler in patients with giant 
cell tumors. Other uses of PMMA bone cement include dental applications, contact and intraocular 
lenses, and filler material for bone cavities and skull defects. 
Bone cements have a powder component and a liquid component that are mixed by the user just 
prior to delivery of the bone cement  
                                                          
1 Yi Zhan, Jianzhong Jiang, Haifen Liao, Haitao Tan, Keqin Yang. Risk Factors for Cement Leakage After 
Vertebroplasty or Kyphoplasty: A Meta-Analysis of Published Evidence. World Neurosurgery [World Neurosurg] 
2017 May; Vol. 101, pp. 633-642 
2 Wang H, Sribastav SS, Ye F, Yang C, Wang J, Liu H, Zheng Z. Comparison of Percutaneous Vertebroplasty and 
Balloon Kyphoplasty for the Treatment of Single Level Vertebral Compression Fractures: A Meta-analysis of the 
Literature. Pain Physician. 2015 May-Jun;18(3):209-22. Review 

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4.2. 
Purpose 
Medtronic (Shanghai) Management Co., Ltd. is sponsoring the Xpede study in China.  This study is a 
prospective, multi-site, randomized, single blinded, human clinical trial.  The purpose of this clinical 
study is to confirm the efficacy and safety of the Kyphon®Xpede™ Bone Cement in human use in 
China. This study is expected to begin as a pre-market study using investigational product in China.  

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Figure 1: Study Flowchart 

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5. Objectives and Endpoints 
5.1. 
Objectives 
5.1.1. 
Primary Objective(s) 
To demonstrate that Kyphon®Xpede™ Bone Cement is effective by showing that: 
- 
the mean change of NRS score from baseline assessed at 6months post operation  in the 
subjects treated with Kyphon®Xpede™ Bone Cement is non-inferior to that in the subjects 
treated with Mendec Spine Bone Cement;  
- 
Change in Vertebral Body Angles from baseline at 6 months in the subjects treated with 
Kyphon®Xpede™ Bone Cement is non-inferior to that in the subjects treated with Mendec Spine 
Bone Cement. 
 
5.1.2. 
Secondary Objective(s) 
To evaluate the secondary endpoints defined in section 5.2.2 
5.2. 
Endpoints 
5.2.1. 
Primary Endpoint(s) 
The primary endpoints   are as follows: 
- 
Change of NRS score at 6 months postoperative from baseline . 
- 
Change of Index Vertebral Body Angles 6 months postoperative from baseline 
 
5.2.2. 
 Secondary Endpoints(s) 
The secondary endpoints include: 
• 
Change of NRS score from baseline at 1 day and 3 months 
• 
Change of ODI from baseline at 1 day, 3-month visit and 6-month visit. 
• 
Change of SF-36 from baseline at 1 day, 3-month visit and 6-month visit 
• 
Change in Vertebral body height restoration at 1 day and  3-month visit and 6 month 
• 
Change in Vertebral body Angles from baseline at 1 day, 3-month visit 
• 
Adverse event through 6-month visit, in particular, the following events will be reported: 

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- 
Bone Cement Implantation Syndrome; 
- 
Bone Cement leakage; 
- 
Vertebral body compression fracture; 
- 
Adjacent vertebral body fracture; 
6. Study Design  
The Xpede Study is a prospective, 1: 1 randomized, single blinded, multi-center human clinical trial 
designed to confirm the safety and efficacy profile of the Kyphon®Xpede™ Bone Cement for 
regulatory approval in China.  This study will enroll up to 180 subjects in order to demonstrate that 
the Kyphon®Xpede™ Bone Cement is non-inferior to the Mendec Bone Cement by more than a 
small pre-specified amount in terms of the primary endpoint. This amount is defined as the non-
inferiority margin (section 13 for details). Subjects will be randomly assigned with a 1:1 ratio to the 
Kyphon®Xpede™ Bone Cement arm or to the Mendec Bone Cement arm and then followed for a 
duration of 6 months in all sites. All study sites will be in China. All study sites and Investigators are 
provided under a separate cover.   
6.1. 
Duration 
It is expected to enroll 180 subjects in 3 sites in China. The estimated time of enrollment is 
anticipated to be approximately 6 months in total. Subjects will be followed during a period of 6 
months after the study procedure so the estimated participation duration of each subjected is 
estimated to be 6 months. The total duration of the study is anticipated to be approximately  12 
months. 
Each study site is expected to enroll a minimum of 2 subjects during the study phase. In order to 
minimize potential bias associated with single center experience, a study site is limited to enroll no 
more than 90 (50%) of the total study enrollments (180). Each clinical trial institution, in principle, 
should launch and terminate clinical trials over the same period 
6.2. 
Rationale  
The goal of this study is to confirm the efficacy and safety of the Kyphon®Xpede™ Bone Cement. A 
prospective, randomized trial comparing the Kyphon®Xpede™ Bone Cement   with a bone cement 
currently available in China with comparable characteristics and materials (Mendec Spine – Tecres, 
Verona, Italy) was designed to meet this objective  

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7. Product Description 
7.1. 
General 
Percutaneous vertebroplasty and kyphoplasty are minimally invasive techniques intended to be 
used for pathological fractures of the vertebral body.  During this study either the Kyphon®Xpede™ 
Bone Cement or the currently available cement (Mendec Spine – Tecres, Verona, Italy) will be used. 
The Kyphon®Xpede™ Bone Cement is provided as a powder and a liquid which will need to be 
combined into a KYPHON™ Mixer. Following the KYPHON™ Mixer Instructions For Use, the powder 
and liquid components should be mixed for at least 30 seconds ensuring the ingredients are 
smoothly and uniformly combined. The liquid must moisten all the powder. When the bone cement 
is in a doughy state, it has reached the appropriate level of viscosity and is ready to be placed into 
the pathological fracture. The aim of the injection of bone cement is to stabilize the fractured 
vertebral body by filling the bony trabeculae. 
 
Refer to Kyphon®Xpede™ Bone Cement additional details regarding directions for use, indications, 
contraindications, warnings and/or precautions. In this trial, the Kyphon®Xpede™ Bone Cement will 
not be tested for the fixation of pathological fractures of the sacral vertebral body or ala using sacral 
vertebroplasty or sacroplasty as stated in the most recent Instruction for use.  
Mendec Spine is currently approved for the use in China and will be used according to its approved 
indications. 
 
Table 1: Products information 
Model 
Number 
Component 
Investigational or 
Commercially Available  at 
Study Start  
CX01A 
Kyphon®Xpede™ Bone 
Cement 
Investigational  
13C2040 
Mendec  
Commercially available 
 
Mendec will be used as comparator due to its similar characteristics as shown in Table 2 
 

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Table 2: Products Characteristics 
 
Mendec 
Kyphon®Xpede™ 
Bone Cement 
Power  
20g 
20g 
Polymethlmethacrylate 
67.5% 
69.1% 
Barium sulphate 
30% 
30% 
Benzoly peroxide  
2.5% 
0.9% 
Liquid  
9g 
9.4 g 
Methylmethacrylate 
99.1% 
99.4% 
N,N-dimethyl-p-
toluidine 
0.9% 
0.6% 
Hydroquinone 
75ppm 
75ppm 
 
 
7.2. 
Manufacturer 
Xpede™ Bone Cement : Medtronic SOFAMOR DANEK USA, INC.  1800 Pyramid Place, Memphis, TN 
USA 38132.  
7.3. 
Packaging 
Xpede™ Bone Cement will be labelled as per local regulations in China and products requiring 
investigational labelling will be labelled investigational as per local regulatory requirements. 
7.4. 
Intended Population 
KYPHON™ Xpede™ Bone Cement is indicated for the treatment of pathological fractures of 
the vertebral body due to osteoporosis, cancer, or benign lesions using a cementoplasty (i.e. 
kyphoplasty or vertebroplasty) procedure. It is also indicated for the fixation of pathological 
fractures of the sacral vertebral body or ala using sacral vertebroplasty or sacroplasty. Cancer 
includes multiple myeloma and metastatic lesions, including those arising from breast or lung 
cancer, or lymphoma. Benign lesions include hemangioma and giant cell tumor. Pathological 
fracture may include a symptomatic microfracture (as documented by appropriate imaging 
and/or presence of a lytic lesion) without obvious loss of vertebral body height. 
7.5. 
Contraindications 
PMMA bone cement is contraindicated in the presence of active or incompletely treated infection at 
the site where the bone cement is to be applied, for treatment of non-pathological, acute traumatic 

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fractures of the vertebra or sacrum, and in cases involving either displaced sacral fractures or 
compromise of the sacral foramina. 
7.6. 
Product Use 
The handling characteristics of bone cements are affected by operating room conditions, including 
the room temperature, temperature of the cement components prior to mixing, humidity, the 
geometry of the mixing apparatus, time spent mixing, and the geometry of the delivery device. Any 
change in one or more of these conditions can alter the handling characteristics of the bone cement, 
including the following: 
• 
Handling period – the time it takes for the bone cement to reach the doughy state (the 
cement has reached the doughy state when it no longer sticks to surgical gloves). 
• 
Working period – the time the bone cement remains in the doughy state, and can be 
delivered. 
• 
Hardening period – the time it takes for the bone cement to harden or until it can no longer 
be delivered. 
The user must be aware of these factors and adjust technique to account for variability in operating 
room conditions. 
Under specific conditions in our laboratory using the KYPHON® Cement Delivery System, 
KYPHON®  Xpede™ Bone Cement, had the following dough time, hardening time and working 
period, which allowed sufficient time for careful, minimally-invasive surgical introduction of the bone 
cement. 
Table 3: Dough time, hardening time and working period informations 
Average 
Room Temperature at 
Start of Mixing (±1°C) 
Average Dough Time 
(minutes) 
Average 
Hardening 
Time (minutes) 
Average 
Working 
Period (minutes) 
15 
12.8 
42.8 
30.0 
19 
5.8 
21.9 
16.1 
23 
2.4 
15.8 
13.4 
26 
2.0 
13.3 
11.3 
 
Lower temperatures or other changes in operating room conditions can increase the handling, 
working (doughy), and hardening periods. Conversely, higher temperatures or other changes in 
operating room conditions can decrease the handling, working (doughy), and hardening periods. 

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Table 4: Handling Characteristics of KYPHON®  Xpede™ Bone Cement at 23 ± 1°C  
Period 
Activity 
Approximate Cumulative Time 
From Initiation of Mixing* 
Mixing 
Mix liquid and powder 
0-1 minutes 
Handling 
Transfer into delivery system 
1-2 minutes 
Working (doughy state) 
Fill vertebral body 
2-16 minutes 
Hardening 
Wait 
before 
completing 
procedure 
16-20 minutes 
 
 
When the bone cement is in a doughy state, it has reached the appropriate level of viscosity and is 
ready to be placed into the pathological fracture. Do not insert the bone cement into the vertebral 
body until the bone cement has reached the doughy state. 
Note: These cumulative time periods will vary depending on temperature and other factors. For 
example, the colder the environment, the longer the time necessary for the cement to develop the 
required doughy consistency. Warmer temperatures require more rapid preparation and handling. 
Ensure the cement’s viscosity is high enough (doughy) before delivery begins. The doughy state is 
when the bone cement does not stick to surgical gloves. 
* 
These times are based on cement prepared in Medtronic Spine LLC’s laboratory. Times were 
obtained from bone cement mixed in a KYPHON® Mixer and delivered through the KYPHON® 
Cement Delivery System. Times may vary when other mixing methods, delivery devices and vacuum 
are used. 

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Figure 2: The effect of room temperature on the handling characteristics of KYPHON® Xpede™ 
Bone Cement is shown in the above time vs. temperature graph. At room temperatures of 15°C, 
19°C, 23°C and 26°C, units of KYPHON® Xpede™ Bone Cement were mixed in a KYPHON® Mixer and 
transferred to KYPHON® Cement Delivery System. Dough time and hardening time were 
measured. The dashed line represents dough time (when dispensed cement no longer sticks to a 
surgical glove) and the solid line represents hardening time (when cement is too hard to dispense). 
Preparation Procedures Per the note above, temperature can affect the handling of the cement. 
Prior to use, it is advised to keep the product at a temperature of 23 ± 1°C for a period of 24 hours. 
Prior to use, KYPHON® Xpede™ Bone Cement packaging should be examined for damage and the 
presence of all required components. Maintain aseptic transfer surgical technique to prevent 
possible infection. Maintain strict adherence to the instructions for mixing the powder and liquid to 
prevent possible dermatitis from the liquid monomer during handling. Assure that the inner package 
is undamaged, that the powder is not discolored (yellow or brown) and the liquid is not syrupy. These 
conditions indicate that the product has not been stored correctly. Assure that the preparation 
accessories are specifically compatible with the bone cement product. Do not open the vial of liquid 
over the mixing bowl to avoid the risk of glass fragments entering the dough. 
• 
Never add other substances or foreign bodies to the acrylic resin. Never modify the ratios between 
the liquid and solid components. 
• 
Care should be taken in the mixing of the liquid and powder components such that the entire contents 
of the vial and packet are utilized. The liquid monomer and the powder component should be 
thoroughly mixed. 
Mixing Procedure: 

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1. Always use sterile technique when mixing the bone cement. 
2. Open powder packet and break open the vial. Immediately combine the powder and liquid into a 
KYPHON® Mixer. 
3. Following the KYPHON® Mixer Instructions For Use, mix the powder and liquid components for at 
least 30 seconds ensuring the ingredients are smoothly and uniformly combined. The liquid must 
moisten all the powder. 
4. After the powder and liquid have been thoroughly mixed, the transfer of the mixture into a cement 
delivery device(s) may begin. 
 
Clinical Application Procedures: 
When the bone cement is in a doughy state, it has reached the appropriate level of viscosity and is 
ready to be placed into the pathological fracture. Do not insert the bone cement into the vertebral 
body until the bone cement has reached the doughy state, as described below. 
 
 
1. Dispense a fresh sample of about 2 cm of cement on to a surgically gloved finger (Fig. A). 
2. Very gently touch the surface of the cement with a surgically gloved finger (Fig. B). 
3. If the cement sticks to the glove and/or fibers (fine, hair-like threads) are observed to form 
between the fingers (Fig. C), then the cement has not yet reached the doughy state. In this 
case, repeat the previous steps at 30 second intervals. 
4. When the gloved fingers separate cleanly with no fibers observed (Fig. D), the cement has 
reached the doughy state and is ready to be injected into the vertebral body. 
5. Delivery of the bone cement into the vertebral body should begin in the anterior or central 
region of the vertebral body. Continue by allowing the bone cement to flow into the posterior 
area without moving the delivery device posteriorly. Care should be taken to avoid placing 
the delivery device against the anterior cortex. 
6. While the bone cement hardens, it is important to maintain patient positioning until the end 
of the polymerization or hardening process. 
 
The procedure may require technical support from Medtronic. The technical support is part of the 
standard of care to provide guidance on the appropriate use of the devices according to the IFU and 
Investigator Brochure. If support is present, it will be recorded on the Sponsor Technical Support 
List Product Training Requirements 

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The insertion of bone cement is part of routine BKP and VP procedure thus do not require any special 
training prior to the study. However, to ensure the quality of the study and minimize the investigator 
effect on study endpoints, prior to performing the procedure, it is important that surgeons read and 
understand the Instructions for Use that accompanies the Kyphon®Xpede™ Bone Cement.  
Additionally, the selection of investigators should follow the criteria: 
• 
All investigators should be trained by Medtronic on the appropriate use of Kyphon®Xpede™ 
Bone Cement. 
• 
Investigator is qualified by training and expertise in the diagnosis and treatment of subjects 
requiring a BKP or VP procedures. 
• 
investigator has associate senior professional title or qualification or above in the clinical trial 
institution (CFDA Order No. 25 Article 61) 
• 
Investigator and clinical research staff have experience with conducting clinical device study 
that comply with applicable regulatory standards studies and have the time to conduct the 
study in accordance with the investigational plan. 
• 
Agreement to comply with the investigational plan and applicable regulatory requirements. 
• 
Adequate volume of potential subjects who meet the eligibility criteria 
• 
Number of simultaneous competing clinical studies that might interfere with subject 
enrollment or study conduct. 
• 
Appropriate facilities, resources, and equipment. 
• 
Willing to undergo monitoring, auditing or inspection by Medtronic or relevant regulatory 
authorities. 
7.7. 
Product Receipt and Tracking 
Investigational product will be distributed to a site only when Medtronic has received all required 
documentation, has notified the site of site activation and the site has been authorized to enroll in 
the study. Distribution of the investigational product to study sites during the clinical study will be 
managed by Medtronic. The Investigator or site representative will verify that Investigational 
product supplies are received intact and in the correct amounts.  This will be documented by 
signing and dating the Proof of Receipt or similar document.  
Investigational products will be used only in the study according to the CIP.  
7.8. 
Product Storage 
KYPHON® Xpede™ Bone Cement should be stored in its original shipping materials. Proper care 
should be taken to ensure that KYPHON® Xpede™ Bone Cement will not be damaged. Store below 
25°C and away from sunlight. 

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7.9. 
Product Return 
The unused package of Xpede™ Bone Cement will be returned to Medtronic at end of every 
procedure. Please refer to your local Medtronic field personnel to arrange the return of the products. 
7.10. Product Accountability  
Device Disposition logs will be provided to the site and will be used for tracking of all investigational 
products.  
These logs must be maintained at each investigational site to ensure traceability via assigned lot or 
serial numbers. It is the responsibility of the investigator to correctly handle, and track the 
investigational products. Disposition of investigational product will be reported when any of these 
investigational products are received, opened, implanted, disposed of or returned to Medtronic and 
completed in the related Investigational Products tracking documentation.  
In addition, the used/residual/opened bone cement will be destroyed as medical waste on site 
according as to local procedures or regulations. All empty outer investigational product packaging 
will be inventoried by the site and verified by the site monitor. After investigational product 
accountability has been completed by the site monitor, empty packaging will be destroyed on site 
according to local procedures or regulations. 
At the end of the procedure, the unused package of Xpede™ Bone Cement will be returned to 
Medtronic. 
Mendec Bone cement will be distributed, handled, stored and returned according to each site 
standard procedure.  
 
8. Selection of Subjects 
8.1. 
Study Population 
Up to 180 patients diagnosed with pathological vertebral body fracture and indicated for a BKP or VP 
procedure will be enrolled in up to 3 sites in China.  
8.2. 
Subject Enrollment 
Ethics Committee approval of the Xpede Study Clinical Investigation Plan and Informed Consent 
Form must be obtained prior to enrolling patients in the study.  

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Subjects are considered enrolled in the study upon signing the informed consent and meet all of 
the inclusion and none of the exclusion criteria.  Informed consent must be obtained prior to 
performing any study-related procedures. Subjects will be assessed to ensure that they meet all of 
the inclusion and none of the exclusion criteria.  
8.3. 
Inclusion Criteria 
Subjects will be included if ALL of the following inclusion criteria are met: 
1) Subject being diagnosed as having painful pathological vertebral body fracture, who is suitable for 
VP/BKP procedure (1-3 levels) according to clinic practice. 
2) Subjects who are willing to participate in study through consent and willing to undergo study 
specific required procedures with expectancy of geographically stable for follow up duration. 
3) ) Subjects are at least 18  and ≤80 years old. 
8.4. 
Exclusion Criteria 
Subjects will be excluded if ANY of the following exclusion criteria is met: 
1) Subject has a local or systemic infection 
2) Subject has pains caused by other spine disease than pathological vertebral compression fracture 
3) Subject has a medical condition with less than 1 year of life expectancy 
4) Subject is grossly obese, i.e. BMI≥40 
5) Subject has medical conditions that represent contraindications for the use of bone cement by 
investigator’s decision 
6) Subject has an allergy or an intolerance to bone cement component 
7) Subject has past spinal surgeries at the target  level(s) for which the VP/BKP procedure is suitable.  
8) Subjects who are currently enrolled or planning to participate in a potentially confounding drug or 
device trial during the course of this study.  Co-enrollment in concurrent trials is only allowed when 
document pre-approval is obtained from the Medtronic study manager and Medtronic Medical 
Advisor. 
9) Pregnant women or breastfeeding women, or women of child bearing potential and who are not 
on a reliable form of birth regulation method or abstinence. 

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10)Subjects with exclusion criteria required by local law (age or other). 
11)Subjects with medical condition which precludes patient from participation in the opinion of the 
Investigator 
 
9. Study Procedures  
9.1. 
Schedule of Events 
Table 5: Schedule of Events 
                                                          
3To be obtained before any study related procedure 
Data to be collected 
Baseline 
& 
Randomization 
Study Procedure 
(Day 0) 
1 
day 
Post 
Operative  
3 months post op 
6 months post op 
Unscheduled 
Visit windows 
 
Can 
be 
perfor
med 
the 
same 
day of 
baseli
ne 
(After 
24hour
s 
but 
not 
later 
than 1 
week) 
±2 
weeks 
±2 
weeks 
 
 
NA 
Inclusion/Exclusion 
criteria  
X 
 
 
 
 
 
Informed 
Consent 
Form3 
X 
 
 
 
 
 
Demographics 
and 
medical history 
X 
 
 
 
 
 

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9.2. 
Subject Consent 
Informed consent is defined as legally effective, documented confirmation of a subject’s (or their 
legally authorized representative or guardian) voluntary agreement to participate in the study.  The 
Patient Informed Consent Form (ICF) is signed only after all relevant information regarding all 
aspects of the clinical study that are relevant to the subject's decision to participate throughout the 
clinical study have been provided to the subject.  Subject consent will be obtained in accordance with 
local law and regulations.  The ICF must be approved by the sponsor and the site’s EC. The 
Physical examination 
X 
 
 
 
 
 
MRI 
X 
 
 
 
 
 
Study Procedure Data 
 
X 
 
 
 
 
Concomitant specific 
medication 
X 
 
X 
X 
X 
X 
NRS score 
X 
 
X 
X 
X 
X 
ODI 
X 
 
X 
X 
X 
X 
AP/Lateral X-ray 
X 
 
X 
X 
X 
X 
SF36 
X 
 
X 
X 
X 
X 
Device disposition 
 
X 
 
 
 
 
Adverse 
events 
review (subject and 
non-subject) 
and 
death information 
Upon Occurrence 
Device 
Deficiency 
review 
Upon Occurrence 
Protocol 
deviation 
review   
Upon Occurrence 
Reason for premature 
study termination 
Upon Occurrence 

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documents referenced must be maintained in such a way as to assure control of the document (i.e. 
version and/or date) such that the version(s) approved by the EC are clear with a documented 
change history for all revisions. The principal investigator or his/her authorized designee will 
conduct the informed consent process. Refer to Appendix E: Informed Consent Templates. 
The process for obtaining informed consent shall: 
• 
Avoid any coercion of, or undue influence of subjects to participate 
• 
Not waive or appear to waive subject’s legal rights 
• 
Provide documents to the subject in a language s/he is able to read and understand 
• 
Use language that is non-technical and understandable to the subject or legal representative 
• 
Provide ample time for the subject to consider participation 
• 
Include a dated signature of the subject or legal representative acknowledging their 
participation in the study is voluntary. Include personally dated signatures of the principal 
investigator or an authorized designee responsible for conducting the informed consent process. 
• 
The informed consent shall be documented before any procedure specific to the clinical 
investigation is applied to the subject. 
In the event that the subject can’t read or write, a witnessed (impartial third party) consent form and 
authorization/data protection will be allowed (as determine by local law), provided detailed 
documentation of the process is recorded in the subject’s case history and the witness signs and 
dates the appropriate consent form and authorization.   
The signed ICF and the authorization must be filed at the site.  A copy of the ICF must be provided to 
the subject.  The original signed ICF and the authorization or other privacy language where required 
by law must be retained and made available for review by site monitors, auditors, or inspectors. 
The consent process should be documented at each site in source documents which may include 
Medical charts, progress notes of medical history sheets, etc. Any changes to a previously approved 
Informed Consent Form throughout the course of the study must be approved by Medtronic and 
then by the Ethics Committee reviewing the application before being used to consent a prospective 
study subject. The document(s) must be controlled (i.e. versioned and/or dated, per local law) to 
ensure it is clear which version(s) were approved by the Ethics Committee. All important new 
information should be provided to new and existing subjects throughout the study, and if relevant, 
all affected subjects shall be asked to confirm their continuing informed consent in writing.   

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9.3. 
Stratification and Treatment Assignment 
Randomization will be performed according to a randomization schedule developed by the sponsor 
or sponsor’s representative after the subject has signed the Informed Consent and prior to the 
surgical procedure. The clinical database will contain the randomization distribution system which 
will be used for this study. 
Individuals who are randomized and receive the study treatment will be considered study (treated) 
subjects; only data from study (treated) subjects will be included in endpoint analysis. 
Patients will be randomized 1:1 to either  Xpede™ Bone Cement or Mendec bone cement. The 
sequence of treatments will be randomly permuted in blocks of 2 or 4 patients per block. The blocked 
randomization will be centralized and schedules will be created by the study statistician using 
statistical software. The randomization will be performed by the center via the EDC system (Oracle 
Clinic). To minimize the selection bias, the randomization procedure for this study will use the site (3 
sites), the number of vertebral to be treated (1,2 or 3) and the type of procedure (2 procedure: VP 
and BKP) as stratification factors, so that there will be a separate permuted block randomization list 
for each stratum (18). This guarantees treatment balance within strata. 
9.4. 
Baseline 
Informed consent must be obtained prior to performing any study-specific procedure. 
The following information will be collected at baseline: 
• Demographic data 
• Medical history,  
• General physical examination 
• MRI 
• Imaging: A/P x ray imaging 
• Concomitant medication  
• All Adverse Events 
• Subject will complete: 
a.NRS 
b.Quality of life questionnaires: SF-36 v2 
c. Performance Status: Oswestry Disability Index (ODI) v2.1a: 

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Spinal disability will be assessed with the ODI questionnaire. The ODI is registered with the 
International Consortium for Health Outcome Measures as a standard outcome measure4. It is 
specific for spinal disorders and considered as the “gold standard” by several systematic reviews5 6 
7,  and recent surgery guidelines8  and has been used in several studies of spinal metastases5. 
9.5. 
Prior and Concomitant Medications 
All medication therapy for optimal medical care will be given during the study period at the discretion 
of the physician(s). The specific concomitant medications listed below should be documented as 
concomitant medication. 
• Analgesic(s) frequency and dose in past 24-hours will be recorded. All pain management (including 
but not limited to Nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, acetyl salicylic 
acid, tramadol, cannabinoids) will be collected. All opioid analgesics will be converted to oral 
morphine equivalent doses (OMED). Non-opioid analgesics will be counted as zero for OMED and will 
be analyzed separately. 
• Concurrent Osteoporosis medication(s): Study subjects who have concurrent osteoporosis will 
be 
treated 
with 
antiresorptive 
therapy 
(e.g., 
bisphosphonates, parathyroid hormone 
(PTH),calcitonin), calcium and vitamin D as needed according to standard of care. 
. 
9.6. 
Procedure day 
The following  information will be collected during the procedure: 
                                                          
4 Fairbank JC. Why are there different versions of the Oswestry Disability Index? J Neurosurg Spine. 2014 
Jan;20(1):83-6.  
5 Fairbank JC, Pynsent PB. The Oswestry Disability Index. Spine (Phila Pa 1976). 2000 Nov 15;25(22):2940-52; 
discussion 2952. Review 
6 Johnsen LG, Hellum C, Nygaard OP, Storheim K, Brox JI, Rossvoll I, Leivseth G, Grotle M. Comparison of the SF6D, 
the EQ5D, and the oswestry disability index in patients with chronic low back pain and degenerative disc disease. 
BMC Musculoskelet Disord. 2013 Apr 26;14:148.  
7 Gum JL, Glassman SD, Carreon LY. Clinically important deterioration in patients undergoing lumbar spine surgery: 
a choice of evaluation methods using the Oswestry Disability Index, 36-Item Short Form Health Survey, and pain 
scales: clinical article. J Neurosurg Spine. 2013 Nov;19(5):564-8 
8 Ghogawala Z, Resnick DK, Watters WC 3rd, Mummaneni PV, Dailey AT, Choudhri TF, Eck JC, Sharan A, Groff MW, 
Wang JC, Dhall SS, Kaiser MG. Guideline update for the performance of fusion procedures for degenerative disease 
of the lumbar spine. Part 2: assessment of functional outcome following lumbar fusion. J Neurosurg Spine. 2014 
Jul;21(1):7-13 
 

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• 
Overall duration of the study procedure (skin to skin) 
• 
Fluoroscopy duration 
• 
Level(s) treated 
• 
Type of anesthesia utilized 
• 
Approach: unilateral versus bilateral BKP/VP 
• 
BKP data including Balloon inflation volumes and pressures 
• 
Kyphon® Xpede™ Bone Cement/Mendec volume 
• 
Cement delivery system use 
• 
All Adverse Events/Device Deficiencies 
• 
Cement extravasation 
• 
Inpatient versus outpatient status 
• 
Length of stay 
9.7. 
Follow up visits 
Information collected post-treatment at 1 day and 3 and 6 months onsite follow-up visits for all 
subjects by the Investigator (or, if delegated, the Study Nurse/Coordinator) includes the following: 
• Concomitant medications 
• Re-intervention at initially treated level(s), if applicable 
• Imaging: A/P x ray imaging will be collected at onsite follow-up visits  
• All adverse events/device deficiencies 
• Subject will complete: 
a.NRS score 
b.Quality of Life questionnaires: SF-36 v2 
c. Performance Status: ODI v2.1a 
9.8. 
Radiography assessment 
Radiological measurements will be made both by the blinded site personnel and by a centralized, 
independent radiologist (corelab). 
A. Vertebral Body Height 
Vertebral body height should be assessed at Pre-Operative, 1 days, 3-, 6-month. 
Vertebral Body Height in the lateral projection will be measured at each treated vertebra as well as 
the next adjacent vertebrae (superior and inferior) without fracture and reported in millimeters. 
Vertebral Body Height is the distance between comparable points on the superior and inferior 

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endplates of the vertebral body at the posterior (Hp), midline (Hm) and anterior (Ha) locations as 
shown in Figure 3. 
Notes about Adjacent Vertebral Body Height Measurements: 
Note 1:  The normal estimated pre-fracture height of the treated vertebra will be based on the 
average of the nearest adjacent non-fractured vertebrae (see Figure 4 below). The reviewer will 
record the level of the nearest non-fractured level superior to and inferior to the treated level. 
Note 2:  When L5 is the treated vertebra, the estimated pre-fracture (predicted) height of L5 will be 
based on L4 or the nearest superior non-fractured level.  The height of S1 is not suitable as a 
predictor of the pre-fracture height of L5. 
Note 3:  The height of the nearest adjacent, non-fractured, vertebrae may be calculated at a single 
time point and used for all measurements at other time points.  In general, the adjacent level 
vertebral heights will be obtained at the Pre-Operative time point from standing neutral lateral x-
rays. 
Note 4:  In some cases, the superior or inferior adjacent vertebra may be poorly visualized at the 
Pre-Operative visit due to inadequate image quality.  In this situation, the adjacent vertebra may be 
excluded from the analysis, or a subsequent visit, e.g. Post-Operative, may be used to obtain a 
reliable measurement of the adjacent vertebral body height. 
 
 
1) Posterior height (Hp) is obtained by placing a vertical line along 
the dorsal surface of the vertebral body from the posterior point 
of the superior vertebral body endplate to the posterior point of 
the inferior endplate. 
2) Midline height (Hm) is obtained by placing a vertical line along the 
midline of the vertebral body from the midpoint of the superior 
vertebral body endplate to the midpoint of the inferior endplate. 
The height will be measured between the two opposing 
endplates. If the vertebra is tilted or image obliquely giving a 
double endplate appearance in the radiograph, the vertical 
midpoint of the intact endplate lines will be used as the 
reference point for measurement. 
3) Anterior height (Ha) is obtained by placing a vertical line along 
the ventral surface of the vertebral body from the anterior point 
of the superior vertebral body endplate to the anterior point of 
the inferior endplate. 
 

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Figure 3: Vertebral Body Height 
 
 
Figure 4: Examples of Using the Next Adjacent Non-Fractured Vertebra(e) 
 
Magnification Adjustment 
Vertebral Body Height will be adjusted for variation in image scale by the use of a magnification 
marker. The clinical sites are responsible for ensuring the use of magnification markers, provided 
by Medtronic, on all lateral images. Image readers will measure the diameter of the marker and the 

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ratio of the measurement diameter to the true diameter will define the magnification of the image. 
This magnification will be used to adjust all vertebral body height measurements to a common 
scale at each visit. If the marker is not present or not measurable at a particular visit, the reviewer 
may use a stable anatomical feature common with a calibrated visit to make a similar adjustment 
for scale differences. 
 
B. Vertebral Body Angle 
Vertebral body Angle should be assessed at Pre-Operative, 1 days, 3-, 6-month. 
1) Two lines will be drawn, the first line along the superior endplate of the fractured 
vertebral body and the second line along the inferior endplate of the fractured vertebral 
body for each fractured vertebral body. 
2) The angle between these two lines will then be measured. This is shown in Figure 5. 
Negative angles will be associated with a kyphosis (wedge-shaped) vertebral body; 
positive angles will be associated with lordotic (fish-mouthed) vertebral body.  A zero-
degree angle will indicate that the vertebral endplates are parallel.  
 
Figure 5: Example of Measuring Vertebral Body Angle of a Treated Vertebra Vertebral Body 
Angle of Index Fracture 
 
 
9.9. 
Assessment of Efficacy 
Efficacy will be evaluated by the blinded investigator or designed blinded site personnel status of 
primary endpoint and secondary endpoints related with efficacy. 
X-ray images will be reviewed by an independent radiological reviewer (Corelab) who will be blinded  
to the subjects’ treatment groups for each analysis.  

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Adjudications provided both by the site blinded personnel and by the Corelab will be analyzed 
separately and reported in the Clinical Study Report (CSR). Final conclusion will be made according 
to Corelab adjudication. 
 
9.10. Assessment of Safety 
Timely, accurate, and complete reporting and analysis of safety information is crucial for the 
protection of subjects, clinicians, and the sponsor.  Reporting and analysis of safety data are 
mandated by regulatory authorities worldwide.  Medtronic has established Standard Operating 
Procedures (SOPs) to ensure compliance with global regulatory safety reporting requirements.  
Study activities are conducted in accordance with these SOPs. 
All adverse events are collected throughout the duration of this study, starting from the time of 
signing the ICF through study closure.  Adverse Events are to be reported upon site awareness using 
an adverse event CRF, capturing date of the event; date site became aware of the event, diagnosis 
of the event, actions taken, assessment of seriousness, relatedness and outcome.     
Unavoidable Adverse Events (refer to Table 7) need not be reported unless the adverse event 
worsens or is present outside the stated timeframe.  
Adverse Events will be recorded and reported according to local regulatory requirements and are 
outlined in Table 8. It is the responsibility of the Investigator to abide by the adverse event reporting 
requirements stipulated by local law and the sites’ Ethics Committee.  
9.11. Recording Data 
Clinical data will be collected at baseline, operative day, 1 day post-operative, 3-month and 6-month 
post-operative visits. Data will be collected using electronic case report forms (eCRFs) using an 
electronic data management system for clinical studies. Data will be stored in a secure, password-
protected database, which will be backed up nightly. Data will be reviewed using programmed and 
manual data checks. Data queries will be made available to study sites for resolution. At the end of 
the study, the data will be frozen and retained indefinitely by Medtronic. 
Medtronic will oversee all data management functions and provide support if necessary. Leading site 
will be accountable for data management and analysis about the study data in a centralized manner 
according to local regulations. 
. 

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9.12. Deviation Handling 
A deviation is defined as an event within a study that did not occur according to the CIP or the Clinical 
Trial Agreement.  Prior approval by Medtronic is expected in situations where the investigator 
anticipates, contemplates, or makes a conscious decision to deviate. Prior approval is not required 
when a deviation is necessary to protect the life or physical well-being of a subject in an emergency 
or in unforeseen situations beyond the investigator’s control (e.g., subject failure to attend 
scheduled follow-up visits, inadvertent loss of data due to computer malfunction or inability to 
perform required procedures due to subject illness). 
All study deviations must be reported on the Case Report Form regardless of whether medically 
justifiable, pre-approved by Medtronic, an inadvertent occurrence, or taken to protect the subject 
in an emergency. The description of the deviation and justification must be documented.  
Once a deviation has been identified it should be reported to Medtronic as soon as possible. 
Deviations may be identified through numerous sources, including but not limited to: telephone 
conversations, site monitoring, subject record, or data review.  
It is the site’s responsibility to report deviations in compliance with their EC/IRB policies and/or local 
laws.  
For medically justifiable conditions which preempt a subject’s ability to complete a study-required 
procedure, it may be permitted to complete only one deviation which will apply to all visits going 
forward. This may also apply for other unforeseen situations (e.g., the subject permanently refuses 
to complete a study required procedure and the data will not contribute to the primary end point 
analysis).  However, prior approval from Medtronic is required for such situations.   
In the occurrence of a corrupted device interrogation file, Medtronic may request a deviation to 
document that a readable interrogation file is unavailable. Deviations for missing device 
interrogation file(s) and missing or incomplete electrical testing at the same visit may be reported 
on one deviation CRF. 
In the event the deviation involves a failure to obtain a subject’s informed consent, or is made to 
protect the life or physical well-being of a subject in an emergency, the deviation must be reported 
to the IRB and Medtronic within five (5) working days. Reporting of all other study deviations should 
comply with IRB policies and/or local laws and must be reported to Medtronic as soon as possible 
upon the site becoming aware of the deviation. Reporting of deviations must comply with EC 
policies, local laws, and/or regulatory requirements.  
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions (e.g., amend the CIP, conduct additional training, and 
terminate the investigation).  Repetitive or serious investigator compliance issues may represent a 

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need to initiate a corrective action plan with the investigator and site, and in some cases, necessitate 
suspending enrollment until the problem is resolved or ultimately terminating the investigator's 
participation in the study. 
9.13. Subject Withdrawal or Discontinuation  
Every attempt should be made to follow all treated subjects through study closure.  
Upon exiting from the study, no further study data will be collected or study visits will occur for the 
subject.  No study specific medical care will be provided for subjects after the study has been 
completed and subject will be treated according to the standard routine practice after the study 
period. 
All data available through the time of the subject’s exit will be used for analysis. In the event of study 
exit, the investigator should discuss with the subject the plans for future care and treatment. The 
investigator should explain that the subject will continue to receive standard medical care.  
Alternative treatment, such as medication options, or follow-up through standard of care 
procedures instead of study procedures, and medical consequences should also be discussed. The 
investigator must notify the subject of any significant new findings that may become available during 
the course of the study, which are pertinent to the safety and well-being of the subject. 
Exit 
Subjects may be exited from the study for any of the following situations: 
• 
Subject does not meet inclusion/exclusion criteria and has not been treated  
• 
No BKP or VP attempted 
• 
Procedure attempted but no bone cement was injected 
• 
Subject chooses to withdraw from the study 
• 
Investigator deems withdrawal necessary (medically justified or inclusion/exclusion criteria not 
met, failure of subject to maintain adequate study compliance) 
In the event that a subject is exited from the study prior to study closure, all efforts should be made 
to continue following the subject until all unresolved procedure or product related adverse events 
are resolved or they are ongoing and no further actions will be taken. 
. 
Lost to Follow-up 
In the case that the subject is determined to be lost to follow-up, details of a minimum of three 
attempts and the method of attempt (e.g., one letter and two phone records or two letters and one 
phone record) to contact the subject must be recorded. In addition, the requirements set by the 
governing EC/IRB for subjects lost to follow-up must be followed. 

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10. Risks and Benefits 
10.1. Potential Risks 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the life of a 
product, from the business analysis phase through development, market release, and post-market 
surveillance. 
VP and BKP are not investigational procedures and the risk associated with VP or BKP procedures 
are the same as for the one performed per clinical practice. 
VP And BKP are the two procedures that will be used in both the investigational group (Xpede group) 
and the control group (Mendec) and the randomization will be stratified by the procedures. Hence 
the focus of risk and benefit analysis should be purely on the usage of Xpede versus Mendec 
Serious adverse events, some with fatal outcome, associated with the use of acrylic bone cements 
as specified in the IFU include: 
• 
cardiac arrest 
• 
cerebrovascular accident 
• 
myocardial  infarction 
• 
pulmonary embolism 
Other reported adverse events relevant to the anatomy being treated with acrylic bone cements 
include: 
• 
deep or superficial wound infection 
• 
fistula 
• 
hematoma 
• 
hemorrhage 
• 
heterotopic new bone formation 
• 
extravasation of bone cement potentially resulting in but not limited to: 
• 
compression or irritation of nerve structures, such as the spinal cord or nerve roots, causing 
radiculopathy, parasthesia, paraplegia or paralysis and/or; 
• 
introduction into the vascular system resulting in embolism of the lung and/or heart or other 

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clinical sequelae 
• 
pyrexia due to allergy to bone cement 
• 
short-term  conduction irregularities 
• 
thrombophlebitis 
• 
transitory fall in blood pressure 
• 
migration of hardened bone cement bolus 
10.2. Potential Benefits 
The potential benefits of the KYPHON® Xpede™ Bone Cement are consistent with the vertebral 
body fracture therapy provided by similar currently approved Bone Cement. 
Possible benefits of the use of bone cement include vertebral body height restoration, angular 
deformity correction, vertebral body volume increase, reduction in back pain, reduction in the 
number of days per month that the subject remains in bed, improvement in quality of life, 
improvement in ability to perform activities of daily living, subject satisfaction with the procedure, 
improvement in pain and mobility. 
The information gained from this study could result in the improved management of patients 
suffering from Vertebral body fracture. Additionally, information collected from this study may 
assist in the design of new product(s)/therapy(ies) and/or instructions for use. 
10.3. Risk-Benefit Rationale 
KYPHON® Xpede™ Bone Cement had already been approved and widely used in different regions 
around the world, including EU and USA. 
Risks associated with using the KYPHON® Xpede™ Bone Cement are similar to those associated 
with any other approved bone cement used during VP, BKP  procedures.   
For control arm Mendec Spine, it is a NMPA  approved product. So the risks are also similar to using 
any other approved Bone Cement. 
Compared with eligible patients who receive routine hospital care (any approved DES) and do not 
participate in this study, subjects will have very limited extra risks than using any approved DES. 
Based on post market risk analysis and on the published scientific literature on equivalent products 
that are currently on the market and indicated for the same intended use as the KYPHON® Xpede™ 

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Bone Cement, we anticipate that the benefits of using the KYPHON® Xpede™ Bone Cement 
outweigh the risks associated with the use of this product. 
10.4. Probability analysis of success 
The manufacturing system of Medtronic has been tested and proven for many years. The quality of 
the investigational device has been carefully examined and verified before delivery. The 
investigational device has been commercially available globally, including the Europe and many other 
countries. The basic principles, structure composition and materials etc. either comply with the 
international and domestic standards, or have been carefully examined and verified by Medtronic, as 
well as tested, qualified by NMPA  certificated medical device testing organization. The study design 
of this study complies with related NMPA instructions and requirements of ethical review, and all 
potential subjects will be strictly selected according to indications of the investigational device. 
10.5. Probability analysis of failure 
Although regulatory, ethical, scientific and medical requirements have been fully taken into 
consideration, the unanticipated risk in the clinical application of investigational device could lead to 
failure of this study. Potential risks could be reduced with well-trained study staff and strict protocol 
compliance. 
11. Adverse Events and Device Deficiencies 
11.1. Definitions/Classifications 
. 
 
Table 6: Adverse Event Definitions 
Event Type 
Definition 
Adverse Event (AE) 
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 investigational medical device.  
NOTE 1: This definition includes events related to the investigational medical 
device or the comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related 
to investigational medical devices. 

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Event Type 
Definition 
(ISO 14155:20119 section 3.2) 
The medical events with disadvantages occurred during the clinical study, no 
matter whether they are related to investigational medical devices or not. 
(CFDA Order No. 25 Article 93) 
Serious 
Adverse 
Event (SAE) 
Adverse event that  
a) 
led to death, 
b) 
led to serious deterioration in the 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 or prolonged 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, 
c) 
led to fetal distress, fetal death or a congenital abnormality or birth 
defect.   
NOTE: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not considered a 
serious adverse event. 
(ISO 14155:2011 section 3.37) 
Any untoward medical occurrence during the clinical study: results in death or 
serious deterioration in health; life-threatening diseases or injuries; causing 
permanent damage to the body structure or function; requires hospitalization 
or prolongation of hospitalization; requires medical operations or 
intervention 
for 
preventing 
from 
persistent 
or 
significant 
disability/incapacity; results in fetal distress, fetal death, or congenital 
anomaly/birth defect. 
(CFDA Order No. 25 Article 93) 
Adverse 
Device 
Effect (ADE) 
 
Adverse event related to the use of an investigational medical device. 
NOTE 1: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
(ISO 14155:2011 section 3.1) 
Serious 
Adverse 
Device 
Effect 
(SADE) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.  
(ISO 14155:2011 section 3.36) 
                                                          
9 International Standard ISO 14155:2011(E). Clinical investigation of medical devices for human subjects – Good 
Clinical Practice. 

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Event Type 
Definition 
Unanticipated 
Serious 
Adverse 
Device 
Effect 
(USADE) 
Serious adverse device effect which by its nature, incidence, severity or 
outcome has not been identified in the current version of the risk analysis 
report.  
NOTE: Anticipated serious adverse device effect (ASADE) is an effect, which by 
its nature, incidence, severity or outcome has been identified in the risk analysis 
report. 
(ISO 14155:2011 section 3.42) 
Device 
Deficiency(DD) 
 
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance.  
NOTE: Device deficiencies include malfunctions, use errors, and inadequate 
labeling. 
(ISO 14155:2011 section 3.15) 
Any unreasonable risk caused by a medical device in normal use during clinical 
study that may endanger human health or life safety, such as label error, 
quality issues, malfunction and etc. 
 (CFDA Order No. 25 Article 93) 
Adverse Event Relationship Classification 
Causality assessments define the relationship between the use of the medical device (including 
the medical-surgical procedure) and the occurrence of each adverse event.  During causality 
assessment activity, clinical judgment shall be used and the relevant documents, such as the 
Clinical Evaluation Report and the Risk Management Report shall be consulted, as all the 
foreseeable serious adverse events and the potential risks are listed and assessed there. The 
presence of confounding factors, such as concomitant medication/treatment, the natural history 
of the underlying disease, other concurrent illness or risk factors shall also be considered. 
 
The sponsor and the investigators will use the following definitions to assess the relationship of the 
adverse event to the investigational medical device (or comparator) or procedures.  
1) Not related: relationship to the device or procedures can be excluded when:  
- the event is not a known side effect of the product category the device belongs to or of 
similar devices and procedures;  
- the event has no temporal relationship with the use of the investigational device or the 
procedures;  
- the event does not follow a known response pattern to the medical device (if the response 
pattern is previously known) and is biologically implausible;  
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible - and reintroduction of its use (or increase of 
the level of activation/exposure), do not impact on the serious event;  

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- the event involves a body-site or an organ not expected to be affected by the device or 
procedure;  
 
- the event can be attributed to another cause (e.g. an underlying or concurrent illness/ 
clinical condition, an effect of another device, drug, treatment or other risk factors);  
- the event does not depend on a false result given by the investigational device used for 
diagnosis, when applicable;  
- harms to the subject are not clearly due to use error;  
- In order to establish the non-relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the event.  
2) Unlikely: the relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained.  
3) Possible: the relationship with the use of the investigational device is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible.  
4) Probable: the relationship with the use of the investigational device seems relevant and/or the 
event cannot reasonably be explained by another cause, but additional information may be obtained.  
5) Causal relationship: the serious event is associated with the investigational device or with 
procedures beyond reasonable doubt when:  
- the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures;  
- the event has a temporal relationship with investigational device use/application or 
procedures;  
- the event involves a body-site or organ that  
o the investigational device or procedures are applied to;  
o the investigational device or procedures have an effect on;  
- the serious event follows a known response pattern to the medical device (if the response 
pattern is previously known);  
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible);  
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out;  
- harm to the subject is due to error in use;  

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- the event depends on a false result given by the investigational device used for diagnosis, 
when applicable;  
- In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the event.  
 
The sponsor and the investigators will distinguish between the adverse events related to the 
device and those related to the procedures (any procedure specific to the clinical investigation). An 
adverse event can be related both to procedures and the device. Complications of procedures are 
considered not related if the said procedures would have been applied to the patients also in the 
absence of device use/application. 
In some particular cases the event may be not adequately assessed because information is 
insufficient or contradictory and/or the data cannot be verified or supplemented. The sponsor and 
the Investigators will make the maximum effort to define and categorize the event and avoid these 
situations. Where the sponsor remains uncertain about classifying the event, it should not exclude 
the relatedness and classify the event as “possible”.  
 
 
Unavoidable Adverse Event Related to the Procedure:  An Adverse Event inherent to a surgical 
procedure that is expected to occur in all subjects for a projected duration including but not limited 
to the one listed in Table 7. 
Table 7: Unavoidable Adverse Events 
 
Event Description 
Time Frame (hrs) from 
end of Procedure 
Anesthesia related nausea / vomiting 
24 hrs 
Low-grade fever (<100oF or < 37.8oC) 
48 hrs 
Mild to moderate bruising / ecchymosis 
168 hrs (7 days) 
Sleep problems (insomnia) 
72 hrs 
 
Unavoidable events shall not be reported as AE unless the adverse event worsens or is present 
outside the stated timeframe. 
 

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11.1.1. 
Subject Death 
All subject deaths must be reported by the investigator to Medtronic as soon as possible after the 
investigator first learns of the death.  Document the adverse event that led to the subject death on 
an Adverse Event form. Further supporting evidence that is not originally provided by the site may 
be requested by Medtronic to aid in the adjudication of the death. 
 
A copy of the death certificate, if available and allowed by state/local law, should be sent to the 
Medtronic. When a death occurs in a hospital, a copy of the death summary report and all relevant 
hospital records should be sent to the Medtronic, if available. If an autopsy is conducted, the 
autopsy report should also be sent to the Medtronic if available and allowed by state/local law. When 
the death occurs at a remote site, it is the investigative site’s responsibility to attempt retrieval of 
information about the death. In summary, the following data will be collected: 
 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death 
• 
Relatedness to system and/or procedure 
• 
Death summary/hospital records (if available and allowed by local law) 
• 
Autopsy report (if available and allowed by local law) 
• 
Death certificate (if available and/or allowed by local law) 
11.2. Reporting of Adverse Events and Device deficiencies 
Adverse Events will be recorded and reported according to local regulatory requirements and are 
outlined in Table 8. It is the responsibility of the Investigator to abide by the adverse event reporting 
requirements stipulated by local law and the sites’ Ethics Committee. Investigators are required to 
evaluate and document all AEs and Device Deficiencies (per the definitions in Table 6) observed in 
study subjects from the time they enrolled (signed the ICF) until they are no longer participating in 
the study. AEs and Device Deficiencies should be collected for both the study device as well as for 
the comparator. AEs should be followed until one of these criteria is met:  
• 
Until the AE resolves 
• 
Until no further action can be taken for an ongoing AE 
• 
Until the subject exits the trial, or 
• 
Until trial closure 
NOTE: In the case of permanent impairment, continue to follow the event until it stabilizes and the 
overall clinical outcome has been ascertained. 
The investigator is not required to classify USADE.  

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11.3. Emergency contact details 
For emergency contact regarding a  SAE and/or SADE, investigators should contact their Medtronic 
clinical study representative or monitor immediately (refer to the study contact list provided in the 
site’s study documents binder/investigator site file or refer to the contact information provided on 
the title page).  A list of contact information will be kept separately. 
 
 

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AE Reporting Requirements 
 
Table 8: AE reporting Requirements 
For the following events, reporting requirements are: 
• 
Serious Adverse Events (SAE) 
Investigators shall immediately adopt appropriate therapeutic measures for subjects, and 
simultaneously report to the management department of medical device clinical study in 
clinical Research institutions in written form. Management department of medical device 
clinical study shall report to: 
Medtronic 
Immediately  
Local food and drug regulatory authority and health 
and family planning regulatory authority of the 
province, autonomous region and municipality 
directly under the central government where the 
clinical Research institution locates 
Within 24 hours 
Ethics Committee 
Within 24 hours/per EC’s 
requirements 
For the following events, reporting requirements are: 
• 
All other AEs 
• 
All other Device Deficiencies 
Investigators shall record all the adverse events and device deficiencies occurred during 
the clinical study. Investigators shall analyze the reasons for the events with Medtronic and 
document the analysis result in written report, including the comments of continuing. 
Suspending or terminating study, which shall be reported to the Ethics Committee through 
management department of medical device clinical study in clinical Research institutions 
for review.  
To Medtronic 
Submit in a timely manner after the 
investigator first learns of the event. 
To Ethics Committee 
Per EC’s requirements  
For the following events, reporting requirements are: 
• 
Serious Adverse Events (SAE) 
• 
DD with SAE potential  
Medtronic submits to: 
The food and drug regulatory authorities and health 
and family planning competent authorities at the 
same level  
Within 5 working days upon being 
informed 
Other clinical Research institutions and investigators 
participating in the study 
As per local reporting requirement 

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Ethics Committee 
Timely report to EC of the clinical 
Research institution through 
management department of medical 
device clinical study 
 
 
12. Statistical Design and Methods 
Osteoporotic vertebral compression fractures (OVCFs) have gradually evolved into a serious health 
care problem globally. In order to reduce the morbidity of OVCF patients and improve their life 
quality, two minimally invasive surgery procedures, vertebroplasty (VP) and balloon kyphoplasty 
(BKP), have been developed. Both VP and BKP require the injection of bone cement into the 
vertebrae of patients to stabilize fractured vertebra. As such, bone cement as the filling material 
plays an essential role in the effectiveness of these treatments. The study will randomize subjects 
into two arms the Xpede and the Mendec as comparative products. The Mendec Bone Cement has 
been launched on China Market and has very similar composition material with the Kyphon®Xpede 
™ Bone Cement and they are both polymethylmetacrylate (PMMA). 
Due to these reasons the design of this study is a non-inferiority based on the margin δ as the 
maximum acceptable extent of clinical non-inferiority of Kyphon®Xpede™ Bone Cement.  
Since there are two primary efficacy endpoints, the overall sample size will be determined by the 
primary objective that requires the larger sample size. The non-inferiority hypothesis on the NRS 
requires 154 subjects and including 15% of potential loss-to-follow-up, the total sample size for the 
study will be 178 randomized subjects by 1:1 randomization schedule. If we use 3 * 3 * 2 strata, the 
sample size should be 180 to be divisible of 18. Considering an average of 1.35 level per patient (FREE 
trial 72% with 1 level, 21% with 2 levels, 7% with 3 levels10), we should have around 243 levels treated 
on 180 patients. Since the sample size on Angulation lead to 200 levels, and therefore to 162 
subjects, the sample size will be 180 subjects. The study is considered as a success if both primary 
objectives are met.  
    
                                                          
10 Jan Van Meirhaeghe, Leonard Bastian, Steven Boonen, Jonas Ranstam, John B. Tillman, Douglas Wardlaw, on 
behalf of the FREE investigators. A Randomized Trial of Balloon Kyphoplasty and Nonsurgical Management for 
Treating Acute Vertebral Compression Fractures. SPINE Volume 38, Number 12, pp 971–983 

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13. Sample size determination 
13.1. Primary Objective #1 (Efficacy) 
The first primary objective of this study is to demonstrate that the efficacy of XpedeTM Bone cement 
(Experimental group) is not inferior to the MENDEC (Control group) in terms of NRS score improvement at 6 
months (24 weeks) postoperative from baseline.  
13.1.1. 
Background 
Considering that the VAS and the NRS are reproducible and comparable methods for measuring pain, the 
literature search was performed on the VAS. From a Systematic Review aimed to update the evidence base 
for Balloon Kyphoplasty (BKP) and Vertebroplasty (PV) in the management on patients with VCFs, the mean 
preoperative and postoperative VAS scores (standard deviations) were 8.36 (0.78) and 2.68 (1.09), 
respectively11. In a population of osteoporotic fractures or vertebral metastasis after vertebroplasty the VAS 
mean (standard deviation) scores were 7.8 (1.2) before the procedure and 3.5 (1.3) at 6 months follow-up12. 
Another paper based on the assessment of the treatment of spinal metastases, the pre-operative VAS mean 
(standard deviation) score was 6.85 (0.97), which decreased to 6 months 3.58 (1.63) 13. From the KAVIAR 
study14 the estimated standard deviation for NRS is 3.27 (at 3 and 12 months visit). 
13.1.2. 
Sample Size Calculations  
 
Sample size calculations were performed in SAS software (SAS Institute Inc., Cary, NC, USA). A sample size is 
determined such that the non-inferiority of the primary objective is demonstrated that results are not 
appreciably worse in XPEDE arm compared to MENDEC Spine arm. Based on this information the assumptions 
for the sample size are: 
                                                          
11 Gemma Marcucci, Maria Luisa Brandi. Kyphoplasty and vertebroplasty in the management of osteoporosis with 
subsequent vertebral compression fractures. Clinical Cases in Mineral and Bone Metabolism 2010; 7(1): 51-60 
12 Maiettini D., Orgera G., Bisaccia M., Piscitelli L., Laurino F., Meccariello L., Rebonato S., Schiaroli E., Rossi M. and 
Rebonato A.. Percutaneous Vertebroplasty Improves Pain Control and Quality of Life in Patients Suffering from 
Back Pain: A Single Center Experience.  
13 Feng C., Yong-Hui X., Wen-Zhen C., Wei S., Yang G., Bo F. and Difei W. Percutaneous kyphoplasty for the 
treatment of spinal metastases. ONCOLOGY LETTERS 11: 1799-1806, 2016 
14 Dohm M, Black CM, Dacre A, Tillman JB, Fueredi G; KAVIAR investigators. A randomized trial comparing balloon 
kyphoplasty and vertebroplasty for vertebral compression fractures due to osteoporosis. AJNR Am J Neuroradiol. 
2014 Dec;35(12):2227-36. 
 

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• 
The NRS score which ranges from 0 to 10 is assumed to be approximately normally distributed. 
• 
The NRS score is to be assessed at 24 weeks (6 months) after the procedure. 
• 
The NRS at 24 weeks (6 months) is expected to be 3.5 in the MENDEC Spine treatment, and 3.5 or 
more in the Xpede. A difference in NRS score of 1.5 or less is considered clinically unimportant for this 
comparison 15. It is considered the maximum acceptable increase in NRS score compared to the 
MENDEC Spine arm. 
• 
The standard deviation of the NRS score is expected to be approximately 3.27 (the highest value from 
the literatures sited above) for each treatment. Common standard deviation will be assumed for both 
arms. 
• 
The sample size should be sufficient to produce an 80% chance (power) of a significant result at a one-
sided 0.025 significance level. 
The non-inferiority margin “m” that characterizes the largest absolute difference considered to be dismissible 
is defined as 1.5. Since smaller values of NRS are better, the hypotheses are based on lower-tailed test:  
H0:   µX(t) ≥ µM(t) + m       vs      HA:   µX(t) < µM(t) + m        
Where: t is 24 weeks (6 months), µX is the NRS mean score in the Xpede arm, µM is the NRS mean score in the 
MENDEC and “m” is the non-inferiority margin. 
Based on this statistical test and assuming a one-sided type I error rate of 0.025 and a type II error rate of 0.20 
or equivalently, power of 0.80 for the final analysis, it will be claimed that Xpede is not inferior to MENDEC with 
respect to NRS score if the upper bound of the two-sided 95% confidence interval of the difference (µX(t) -
µM(t)) is less than the margin.  
Thus, the non-inferiority hypothesis will require a sample size of 152 (76 per arm) subjects and including 15% 
of potential loss-to-follow-up, the total sample size for the study will be 179 . If we use 3 * 3 * 2 strata, the 
sample size should be 180 to be divisible of 18 (90 per arm).    
13.2. Primary Objective #2 (Efficacy) 
The second primary objective of this study is to demonstrate that the efficacy of XPEDE bone cement 
(Experimental group) is not inferior to the MENDEC (Control group) in terms of Index Vertebral Body Angles 
improvement at 24 weeks (6 months) postoperative from baseline.  
13.2.1. 
Background 
In Cancer Patient Fracture Evaluation (CAFE) study16, the BKP patients’ Index Spinal Deformity was measured 
by Index Vertebral Body Angles (VBA). The mean index VBA was 9.523  (8.751) at baseline and changed to  0.135  
(5.088) and 0.954  (5.626) at respectively 1 month and 12 months .   
                                                          
15 Copay AG, Glassman SD, Subach BR, Berven S, Schuler TC, Carreon LY. Minimum clinically important difference in 
lumbar spine surgery patients: a choice of methods using the Oswestry Disability Index, Medical Outcomes Study 
questionnaire Short Form 36, and pain scales. Spine J. 2008 Nov-Dec;8(6):968-74 
16 James Berenson, Robert Pflugmacher, Peter Jarzem, Jeff rey Zonder, Kenneth Schechtman, John B Tillman, 
Leonard Bastian, Talat Ashraf, Frank Vrionis, for the Cancer Patient Fracture Evaluation (CAFE) Investigators. 
 

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13.2.2. 
Sample Size Calculations 
Sample size calculations were performed in SAS software (SAS Institute Inc., Cary, NC, USA). A sample size is 
determined such that the non-inferiority of the primary objective is demonstrated that results are not 
appreciably worse in XPEDE arm compared to MENDEC Spine arm. Based on this information the assumptions 
for the sample size are: 
• 
The Angulation is assumed to be approximately normally distributed. 
• 
The Angulation is to be assessed at 24 weeks (6 months) after the procedure. 
• 
The Angulation at 24 weeks (6 months) is expected to be 1.2 in the MENDEC Spine treatment, and 1.2 
or more in the XPEDE. A difference in Angulation of 2.5 or less is considered clinically unimportant for 
this comparison (half standard deviation rule). It is considered the maximum acceptable increase in 
Angulation compared to the MENDEC Spine arm. Standard deviation of 5.0 at 1 month from CAFÉ 
study was conservatively used to derive the non-inferiority margin of 2.5. 
• 
The standard deviation of the Angulation is expected to be approximately 5.6 for both arms. Standard 
deviation of 5.6 at 12 months from CAFÉ study was conservatively used as the standard deviation for 
both arms. 
• 
The sample size should be sufficient to produce an 80% chance (power) of a significant result at a one-
sided 0.025 significance level. 
The non-inferiority margin “m” that characterizes the largest absolute difference considered to be dismissible 
is defined as 2.5. Since smaller values of Angulation are better, the hypotheses are based on lower-tailed test:  
 
H0:   µX(t) ≥ µM(t) + m       vs      HA:   µX(t) < µM(t) + m        
Where: t is 24 weeks (6 months), µX is the mean of index VBA l in the XPEDE arm, µM is the mean of index VBA in 
the MENDEC and “m” is the non-inferiority margin. 
Based on this statistical test and assuming a one-sided type I error rate of 0.025 and a type II error 
rate of 0.20 or equivalently, power of 0.80 for the final analysis, it will be claimed that XPEDE is not 
inferior to MENDEC with respect to Angulation if the upper bound of the two-sided 95% confidence 
interval of the difference (µX(t) -µM(t)) is less than the margin. Thus, the non-inferiority hypothesis 
will require a sample size of 160 levels treated and including 20% of potential loss-to-follow-up, the 
total sample size for the study will be 200 levels treated (100 per arm).   Using the same distribution 
of treated levels from FREE trial: 72% with 1 level, 21% with 2 levels, 7% with 3 levels, the required 
subjects will be 200/1.35  = 148. If we use 3 * 3 * 2 strata, the sample size should be 162 to be divisible 
of 18 (81 per arm), which is   smaller than what is required for the first primary objective.  
                                                          
Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body 
compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol 2011; 12: 
225–356 

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13.3. Data analysis and reporting 
The data will be collected from each center in the electronic Case Report Form (eCRF) data base via 
Oracle Clinic. A specific account number will be given to each center to access the system from any 
internet-enabled computer. Access to Internet is required for the sites to enter data into the 
system. User Identification codes will be created to identify data input from each center. The clinical 
data will be entered by the study staff and transmitted to the central database in an anonymous 
format so that the study sponsor will not be able to identify the patient, in accordance with the 
Chinese Data Privacy Directive. Electronic automatic and manual queries will be generated for 
missing, incorrect or doubtful data and sent directly to the study center via Oracle Clinic.  
All the detailed data analyses are described in the Statistical Analysis Plan (SAP). Any change to the 
data analysis methods described in this section and/or the SAP will require an amendment only if it 
changes a principal feature of the study description. Any other changes to the data analysis methods 
will be described and justified in the Final Report or publication. 
Based on the clinical practice in the surgery procedures and number of subjects enrolled per center, 
an investigation of center effect will be investigated including an independent variable for center in 
the model as well as summary statistics if needed. 
13.4. Analysis of Clinical Data 
Patient demographics and baseline characteristics will be presented using appropriate summary 
statistics. This includes mean and standard deviation, minimum, maximum and median with the 
interquartile range [IQR] for continuous variables, and counts and percentages for categorical 
variables. Summary statistics will be reported with maximum 2 decimals, as appropriate. The SAS 
software (SAS Institute Inc., Cary, NC, USA) or any other validated Statistical Software will be used 
to perform statistical analyses. The test for a treatment effect corresponds to showing that the 
upper bound of the two-sided 95% confidence interval (equivalent to the lower bound of a one-sided 
97.5% confidence interval) for µE(t)-µC(t) < margin. Graphical representations will be used as 
deemed appropriate. No adjustments for multiple comparisons or multiple look at data will be 
performed. Outliers and influential observations will be identified via graphical plots and according 
to study team decision and the analysis could be repeated excluding potential outliers. In case of 
missing data, the imputation of missing data will be performed using the most appropriate method 
depending on the pattern of missing in the data and the type of the imputed variable. After the 
imputation of the missing values the models will be rerun.  
The data will be analyzed according to the intention-to-treat principle and a Full Analysis Set (FAS) 
will be used for primary final analysis. The FAS is the patient set containing all the patients included 
in the study that have signed the study Informed Consent and have received the study treatment. A 
secondary analysis could be performed on a Per Protocol Set (PPS). The PPS patients set containing 
all the patients that meet the inclusion/exclusion criteria with no other major protocol deviation that 

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could impact the clinic outcomes and have the 6 months follow-up visits completed. Any patient 
who does not satisfying the inclusion/exclusion criteria or receives the wrong treatment will be 
eliminate from the per-protocol population. Details of endpoints analyses and additional analysis will 
be described in the Statistical Analysis Plan. 
The analyses based on freedom from event at 6 months will be described by means of Kaplan-Meier 
curves. Cox models will be fitted and hazard ratios (HRs) with 95% confidence intervals will be 
computed. The proportional hazard assumptions will be tested by means of Schoenfeld residuals. 
The exposure time (months) will be computed from the date of the index procedure to the date of 
the last available follow-up or date of first event: [(data end – data in)/30.4].  
The rate of event will be computed and reported separately for each group, together with their 95% 
confidence intervals. Rates were compared by means of either a mixed Poisson model or a negative 
binomial regression model (if over dispersion was present). Incident rate ratios (IRRs) and 95% 
confidence intervals were used to compare the two groups. 
Analysis of endpoints based on comparisons between groups on continuous measurements will be 
performed by Student’s t-test or non-parametric test (Mann–Whitney U test) for normal and non-
normal distributions, respectively. Normality will be assessed by means of Shapiro-Wilks test and 
the p-value will be reported. Categorical variable parameter comparisons will be performed using a 
Chi-square test, or a Mantel-Haenszel test for trend for ordinal variables with 3 or more categories.  
The analysis on the first primary endpoint based on NRS will use one measure per patient and the 
comparison will be between the average NRS in both groups. It will be claimed that XPEDE is not 
inferior to MENDEC with respect to NRS score if the upper bound of the two-sided 95% confidence 
interval of the difference (µX(t) -µM(t)) is less than the margin. 
The analysis on the second primary endpoint based on Index Vertebral Body Angles will use multiple 
data points per patient according to the number of levels treated. Assuming not completely 
independence among measures within same patient the analysis will be performed by means of 
Generalized Estimating Equation (or mixed models for repeated measures) using patient as the 
subject. The model will have the Index Vertebral Body Angles as dependent variables and baseline 
value, number of level treated (as the multiple data points) and arm as explanatory variables. All 
assumptions for regression models will be assessed by viewing plots of the residual values. It will be 
claimed that XPEDE is not inferior to MENDEC with respect to Angulation if the upper bound of the 
two-sided 95% confidence interval of the difference (µX(t) -µM(t)) is less than the margin. 
The overall study is considered reached if both the null NI hypotheses are rejected. A separate 
Statistical Analysis Plan (SAP) will be developed prior to data being analyzed to further describe 
statistical methods, pre-specified data handling rules, and pre-specified analyses that will be 
included in the final study reports. Any deviation from the pre-specified statistical analyses will be 
noted in the study report.  

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The Statistical Analysis Plan will include a comprehensive description of the statistical methods and 
analyses to be included in reports that include analysis of endpoints. Any change to the data analysis 
methods described in the CIP will require an amendment only if it changes a principal feature of the 
CIP. Any other change to the data analysis methods described in the CIP, and the justification for 
making the change, will be described in the clinical study report.   
14. Ethics 
14.1. Statement(s) of Compliance 
•This study is a pre-market clinical trial for product registration. The study will be conducted in 
accordance with the laws and regulations of China, including any future applicable laws and 
regulations in China.  
•To protect the rights and welfare of patients, this clinical study will be conducted in compliance 
with the latest version of the Declaration of Helsinki (2013), the Clinical Trial Agreement (CTA) and 
Clinical Investigation Plan, the laws and regulations of China including Good Clinical Practice for 
Medical Devices (CFDA Order No. 25), Announcement of Chinese Regulation  on Filing of Medical 
Device Clinical Trial (2015, No.87) and also including applicable data protection laws. Sites will also 
comply with any additional ethics committee requirements applicable. 
•The sponsor will provide the medical institution with Medical Device Clinical Trial Notice 
•The principles of the Declaration of Helsinki have been implemented through the patient informed 
consent (IC) process, Ethics Committee approval, study training, clinical trial registration, 
preclinical testing, risk-benefit assessment and publication policy. 
•Approval of the CIP or CIP amendments is required from the following groups prior to any study 
procedures at a study site: Medtronic, principal investigators and Ethics Committee. Similarly, 
approval of subsequent revisions to the CIP is required at each study center from the above 
mentioned groups prior to implementation of the revised CIP at that center. 
•Sponsor should be responsible for filing the study to Shanghai Municipal Food and Drug 
Administration after Ethics Committee approval of the current version of the CIP and fully 
executed Clinical Trial Agreement. 
•All products will be labelled as per local regulations in China and products requiring investigational 
labelling will be labelled investigational as per local regulatory requirements. 
•All participating study sites and investigators should make all the study data and study related 
records and including source data/records available for the monitoring, audits work from sponsor 
and inspection from EC and/or Regulatory body per their requirements to ensure the quality of the 
clinical trial.  
•The sponsor shall avoid improper influence on, or inducement to, the subject, monitor, any 
investigator(s) or other parties participating in, or contributing to, the Xpede study. 

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•Sponsor representatives may provide support as required for the study, including technical 
support at site. Sponsor representatives may provide technical support as required for the study 
under supervision of the Principal Investigator, including: 
•Provide study training relevant and pertinent to the involvement of personnel conducting study 
activities and investigator responsibilities. 
Technical support will be under the supervision of a study investigator, but no data entry on the 
eCRF shall be performed by Medtronic personnel or their representatives at sites. 
 
14.2.   Ethics Committee (EC) 
The study will be conducted in accordance with the requirements of local Ethics Committees.  The 
responsible Ethics Committee (EC) at each investigational site must approve the study protocol 
and consent.  Study activities will not commence prior to receipt of documentation of EC approval 
by the site and Medtronic.  The Investigator and study site staff must comply with the 
requirements of their EC. 
Prior to enrolling subjects, each investigational site’s EC will be required to approve all necessary 
study documents including the CIP, the Informed Consent Form (ICF) and any other written 
information to be provided to the subjects.  EC approval of the clinical study must be received in 
the form of a letter and provided to Medtronic before commencement of the study at an 
investigational site.  The approval letter must contain enough information to identify the version 
or date of the documents approved.  If this information is not contained in the approval letter, it 
must be retrievable from the corresponding submission letter. If the EC approval letter is not in 
English, the Medtronic clinical study team must ensure documented review of the letter in English, 
or a translation to English must be obtained. In addition, the approval letter needs to be 
accompanied by an EC roster or letter of compliance, to allow verification that the investigator, 
other site study staff, and/or Medtronic personnel are not members of the EC. If they are 
members of the EC, written documentation is required stating that he/she did not participate in 
the approval process.  Medtronic will prepare the required documents and send them to the 
investigator for reporting to the EC.  Investigators must inform Medtronic of any change in status 
of EC approval once the investigational site has started enrollment.  If any action is taken by an EC 
with respect to the investigation, that information will be forwarded to Medtronic by the 
respective investigator. 
14.2.1. 
  General Study Requirements 
Prior to enrolling any subjects in the study, all requirements need to be fulfilled. Each site must 
have written documentation of site/Investigator readiness, including but not limited to EC 
approval, a signed investigator agreement, and site research personnel training documentation. 
The Investigators shall agree to this protocol and any amendments by signing and dating the 
investigator agreement. 
The participating Investigator is responsible for adhering to this CIP, the Declaration of Helsinki 

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2013, the agreement and the applicable local regulatory requirements. 
14.2.2. 
  Informed Consent and Ethics Committees  
All subjects must provide written informed consent in accordance with approved by the site’s EC and 
Medtronic. A copy of the informed consent form from each site must be forwarded to Medtronic for 
review and approval prior to submitting it to the EC. A sample copy of the informed consent form is 
provided in Appendix 4. Each site must provide Medtronic with a copy of the investigational site’s EC 
approval letter and the EC approved informed consent form. Approvals for the continuation of the 
study at each investigational site must be kept current and notifications forwarded to Medtronic.  
 
14.3. Monitoring  
Medtronic monitors the regulatory and reporting compliance of clinical studies to ensure the overall 
integrity and quality of the data through a combination of the following actions: 
• 
Automated data logic checks 
• 
Statistical analysis to identify data trends or anomalies 
• 
Statistical analysis to identify sites that are outliers relative to other participants 
• 
Source verification using available in-house data e.g. data transmission   
• 
Regulatory and reporting compliance trends 
• 
Interim on-site clinical monitoring visits 
• 
Site Audits  
It is the responsibility of Medtronic to ensure proper monitoring of this study per regulations.  
Trained Medtronic personnel or delegates appointed by Medtronic may perform study monitoring 
activities to ensure this study is conducted in accordance with the protocol, Clinical Trial Agreement, 
and applicable regulatory and local requirements.   
Medtronic (or delegates) must be allowed access to the subjects’ case histories when conducting 
onsite interim monitoring visits (clinic and hospital records, and other source data/documentation) 
upon request as per the Informed Consent Form, Research Authorization (where applicable) and 
Clinical Trial Agreement. 
Site Monitoring Visits 
Frequency of onsite monitoring visits will be based upon subject enrollment, duration of the study, 
compliance, number of adverse events or deviations, findings from previous monitoring visits and 
any suspected inconsistency in data that requires investigation. Regulatory documents may be 
reviewed at each site. Monitoring for the study, including site qualification visits, site initiation visits, 

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interim monitoring visits, and closeout visits, will be done in accordance to the study-specific 
monitoring plan. 
Visits may be conducted periodically to assess site study progress, the investigator’s adherence to 
study requirements regulatory compliance including but not limited to IRB approval and review of 
the study, maintenance of records and reports, and review of source documents against subject 
CRFs. Monitors review site regulatory and study compliance by identifying findings of non-
compliance 
and 
communicating 
those 
findings 
along 
with 
recommendations 
for 
preventative/corrective actions to site personnel.  Monitors may work with study personnel to 
determine appropriate corrective action recommendations and to identify trends within the study 
or at a particular site. 
Further details of monitoring and a list of data which can be recorded directly in the CRF will be given 
in the study specific monitoring plan. The Monitoring Plan will be provided under a separate cover  
14.4. Data Management 
Data will be collected using an electronic data management system.  Data reporting will be 
completed and submitted by the clinician or authorized staff.  All data will be stored in a secure, 
password-protected database.   
Medtronic will review site reported data to monitor data quality, data discrepancies will be created 
as required and forwarded to the site for resolution. Study management reports may be generated 
by Medtronic to monitor data quality and study progress. Site personnel are responsible for the 
timely submission of data and the resolution of discrepancies. 
Reported data elements should be supported in the subject’s case history.  Any time the database 
reported data are the only record, it should be appropriately documented.  In these cases, an 
alternate method of source documentation is highly recommended.   
For products capable of transmitting data, device data uploads/transmissions will be collected for 
Medtronic products only.  This data will be obtained directly from the submitted device file (i.e. 
transmission, etc.) therefore, additional source verification will not be required. 
Medtronic or regulatory authority may audit the site to evaluate the conduct of this study.  The 
Investigator(s)/institution(s) shall allow study-related monitoring, audits, EC/IRB review, and 
regulatory inspection(s) by providing direct access to study source data/documents, and regulatory 
documents. 

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Leading site will be accountable for data management and analysis about the data from each clinical 
research institution in a centralized manner according to local regulations and study requirements. 
Medtronic will oversee all data management functions and provide support if necessary. 
14.5. Direct Access to Source Data/Documents  
When source data verification is performed, the monitor must have direct access to original source 
documentation and/or certified copies of the original source must be provided. Subject completed 
questionnaires are self-reported source documents and data is to be entered into the RDC by the 
site staff directly from the completed original questionnaires. 
If applicable, the Investigator(s)/Institution(s) will permit study-related monitoring, audits, IRB/EC 
review, and regulatory inspection(s), providing direct access to original source data/documents 
and/or certified copies of the original source. 
Where printouts of electronic medical records, are provided as source documents, or where copies 
of source documents are retained as source documents, they should be signed and dated by a 
member of the investigation site team indicating they are a true reproduction of the original source 
document. 
The eCRFs will not serve as source documents.  Source documentation for data elements not 
routinely captured in medical records may vary from site to site: the site may use worksheets if 
identified as source documents. 
15. Study Administration 
15.1. Confidentiality 
All records and other information about subjects participating in this study will be treated as 
confidential. Data will be transferred and processed by Medtronic or a third party designated by 
Medtronic in a key coded form, unless it’s impossible to make it anonymous, for instance, where the 
patient’s name cannot be removed from the data carrier, such as fluoroscopy images.  
Procedures in the CIP require source documentation. Source documentation will be maintained at 
the site. Source documents, which may include worksheets, patient medical records, programmer 
printouts, and interrogation files, must be created and maintained by the investigational site team. 
Medtronic or regulatory authority may audit the site to evaluate the conduct of this study.  The 
Investigator(s)/institution(s) shall allow study-related monitoring, audits, EC/IRB review, and 
regulatory inspection(s) by providing direct access to study source data/documents, and regulatory 
documents. 

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15.2. Liability 
If subjects are physically injured as a result of participation in this study, reasonable and appropriate 
medical treatment will be provided by Medtronic, if such treatment is not already covered by 
subject’s medical insurance according to the local requirements.  The local sponsor Medtronic 
(Shanghai) Management Co, Ltd. is a wholly owned subsidiary of Medtronic, Inc., which as the parent 
company of such entity maintains appropriate clinical study liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable laws and customs concerning 
specific insurance coverage.  If required, a Clinical Study Insurance statement/certificate will be 
provided to the EC. 
Funding for the study will be defined according to the local regulations and must be agreed upon in 
writing by the clinical research institution and Medtronic before the study commences. The 
payments for the study should be appropriate relative to the number of subjects enrolled.  The 
Kyphon®Xpede™ Bone Cement will be provided by Medtronic free of charge for use in this clinical 
study. A reasonable amount of the procedures outside the routine practice done for this clinical 
study will be reimbursed. No any other compensation for the participation in this study will be 
received. 
15.3. Finance 
Funding for the study will be defined according to the local regulations and must be agreed upon in 
writing by the clinical research institution and Medtronic before the study commences. The 
payments for the study should be appropriate relative to the number of subjects enrolled . The 
Xpede bone cement and the Mendec will be provided by Medtronic free of charge for use in this 
clinical study.  
15.4. CIP Amendments 
Approval of the CIP or CIP amendments is required from the following groups prior to any study 
procedures at a study site: Medtronic, principal investigators, geography-specific regulatory 
authorities (if regulatory approval is required) and an independent Ethics Board. Similarly, approval 
of subsequent revisions to the CIP is required at each study center from the above mentioned 
groups prior to implementation of the revised CIP at that center. 
15.5. Responsibilities of all Parties 
Investigator responsibilities will be included in clinical trial agreement and subject responsibilities 
will be available in Informed Consent Form (ICF). Sponsor will undertake all the responsibilities of 
the sponsor as required per local regulations. 

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15.6. Record Retention 
15.6.1. 
Investigator Records 
The investigator is responsible for the preparation and retention of the records cited below. All of 
these records, with the exception of case history records and case report forms, should be kept in 
the Investigator Site File (i.e., the study binder provided to the investigator) or Subject Study Binder. 
CRFs may be maintained and signed electronically within the electronic data capture system during 
the study. Clinical trial institutions shall keep the clinical trial data for at least ten years after the 
completion of clinical trials. 
• 
All correspondence between the EC, sponsor, monitor, NMPA /regulatory authority and 
or the investigator that pertains this study 
• 
Subject identification and enrollment log, and subject screening log, where required per 
local law Subject’s case history 
o Informed Consent 
o Observations of AEs/ADEs/DDs 
o Medical history 
o procedure and follow-up data 
o Documentation of the dates and rationale for any deviation 
• 
All approved versions of the CIP, Informed Consent Form  
• 
Signed and dated Clinical Trial Agreement 
• 
Delegation documentation 
• 
Study training records for site staff 
• 
Any other records that NMPA  and local regulatory agencies require to be maintained. 
• 
Final Study Report including the statistical analysis 
• 
Current Signed and dated CV of PI (and key study team members if required per local 
requirements) 
• 
Device accountability records, Shipping records for investigational devices and clinical–
investigation related documents and materials 
• 
Software disposition logs  
• 
Electronically signed and dated CRFs 
15.6.2. 
Investigator Reports 
The investigator is responsible for the preparation (review and signature) and submission to the 
sponsor of all case report forms, adverse events and adverse device effects (reported per the 
country-specific collection requirements), device deficiencies, deaths, and any deviations from 
study requirements.  If any action is taken by an EC/IRB with respect to this study, copies of all 
pertinent documentation must be forwarded to Medtronic in a timely manner. Reports are subject 
to inspection and to the retention requirements as described above for investigator records. 

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Table 9: Investigator Reports per Medtronic Requirements 
Report 
Submit to 
Description/Constraints 
Clinical trial 
institution and 
Investigator 
Initiated Study 
suspension or 
termination 
Local NMPA 
If it is required to suspend or terminate the trial as the 
clinical trial institution and investigators found that the 
risk outweighs the possible benefits or results have 
been obtained that suffice the judgment of the safety 
and effectiveness of medical device, the investigators 
shall inform the subjects, and make sure appropriate 
treatment and follow-up visits for the subjects, and 
meanwhile report as required with detailed written 
explanation for the suspension and termination. Report 
to the food and drug regulatory authorities of the 
provinces, autonomous regions and municipalities 
directly under the central government if necessary.  
(GCP for Medical Devices, CFDA order No.25 Article 76) 
Failure 
to 
obtain
informed consent 
Sponsor and 
Ethics Committee
Informed consent shall be obtained in writing and 
documented before a subject is enrolled into the clinical 
investigation.  (ISO 14155:2011) 

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Safety Report 
Clinical 
Trial 
Institution 
Sponsor, 
Local FDA or 
Regulatory 
Authority 
For the serious adverse events occurred in clinical trials, 
investigators shall immediately adopt appropriate 
therapeutic measures for subjects, and simultaneously 
report to the management department of medical 
device clinical trials in clinical trial institutions in written 
form, and notify the sponsor in written form. 
Management department of medical device clinical trials 
shall report to corresponding Ethics Committee as well 
as local food and drug regulatory authority and health 
and family planning regulatory authority of the province, 
autonomous region and municipality directly under the 
central government where the clinical trial institution 
locates in written form within 24 hours. In case of death 
of subjects, the investigators and clinical trial 
institutions should provide all the required additional 
information to the Ethics Committee and the sponsor. 
(GCP for Medical Devices, CFDA order No.25 Article 71) 
Deviation 
and 
Progress report 
Management 
Department of 
Medical Device 
Study deviations and progress report should be 
submitted to Management department of medical 
device clinical study then they will submit to Sponsor 
and EC 

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Final report 
NMPA 
, 
Sponsor, 
and 
Clinical 
Trial 
Institution 
Upon 
completion of multi-center 
clinical 
trials, 
investigators of all clinical trial institutions shall issue 
brief summary of clinical trials, respectively, and submit 
it to coordinating investigator together with Case 
Report Form upon review as required for coordinating 
investigator to summarize and complete summary 
report. 
(GCP for Medical Devices, CFDA  order No.25 Article 29（
7）) 
Investigators should, in accordance with the design 
requirements of the clinical trial protocol, verify and 
validate the safety and effectiveness of investigational 
medical devices, and complete the Clinical Trial Report. 
As for multi-center clinical trials, the Clinical Trial Report 
should contain the Summaries of Clinical Trial of all sub-
centers. 
(GCP for Medical Devices, CFDA order No.25 Article 83) 
The Clinical Trial Report should be signed and dated by 
the investigators, and submitted to the sponsor after 
being reviewed, commented, dated and sealed by 
medical device clinical trial administration department 
of clinical trials institutions. 
For multi-center clinical trial, the clinical trial summary of 
each center should be signed and dated by the 
investigators of respective center, and submitted to the 
leading site after being reviewed, dated and sealed by 
the site's clinical trial administration department. 
(GCP for Medical Devices, CFDA order No.25 Article 86) 
 
 
15.6.3. 
Medtronic Records 
Medtronic shall maintain the following (but not limited to) accurate, complete, and current records: 
 
• 
All correspondence which pertains to the studies 
• 
Investigational device tracking documentation 
• 
Signed Clinical Trial Agreements and delegation documentation as well as the signed 
agreements with third party(if applicable) and FD from PI 

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• 
All electronically signed and dated case report forms submitted by investigator, including 
reports of AEs, ADEs and Device Deficiencies, Subject Deaths 
• 
All approved Informed Consent Forms, and other information provided to the subjects and 
advertisements, including translations 
• 
Copies of all EC/IRB approval letters and relevant EC/IRB correspondence and EC/IRB voting 
list/roster 
• 
Names of the institutions in which the Study will be conducted 
• 
Names/contact addresses of monitors 
• 
Statistical analyses and underlying supporting data 
• 
Study final reports 
• 
Sample eCRFs 
• 
All versions of the study protocol and IB 
• 
Training records of site personnel and Medtronic personnel involved in the study 
• 
Sample of labelling attached to investigational products 
• 
Any other records required by the NMPA   
15.6.4. 
Medtronic Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports listed in the 
tables below.  In addition to the reports listed below, Medtronic shall, upon request of reviewing 
EC/IRB or NMPA  or local regulatory authority, provide accurate, complete and current information 
about any aspect of the respective study. 
Table 10: Sponsor Reports 
Report 
Submit to 
Description/Constraints 
Premature 
termination 
or 
suspension of the 
clinical 
investigation 
Clinical 
Trial 
Institution 
Investigator 
Ethical 
Committee 
Local 
Regulatory 
Authority 
For deciding to suspend or terminate clinical trials, 
sponsor shall notify the management department of 
medical device clinical trials of all clinical trial institutions 
within 5 days, and state the rational in written form. 
Management department of medical device clinical trials 
in 
clinical 
trial 
institutions 
shall 
timely 
notify 
corresponding investigators and Ethics Committee. The 
suspended clinical trials shall not be recommenced 
without the approval of Ethics Committee. Upon the 
completion of clinical trials, sponsor shall notify local 
food and drug regulatory authority of the province, 
autonomous region and municipality directly under the 
central government where he locates in written form. 
(GCP for Medical Devices, CFDA order No.25 Article 46) 

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Safety Report 
Local FDA or 
Regulatory 
Authority 
Clinical 
Trial 
Institution 
Investigator 
Ethical 
Committee 
For serious adverse events or the device deficiencies 
possibly resulting in serious adverse events, sponsor shall 
report to the food and drug regulatory authorities and 
health and family planning competent authorities at the 
same level filed within 5 working days upon being 
informed, simultaneously notify other clinical trial 
institutions and investigators participating in the trial, and 
timely report to Ethics Committee of the clinical trial 
institution through management department of medical 
device clinical trials. 
Final report 
Investigators, 
NMPA, 
local 
competent 
authority  
The Clinical Trial Report should be signed and dated by 
the investigators, and submitted to the sponsor after 
being reviewed, commented, dated and sealed by 
medical device clinical trial administration department 
of clinical trials institutions. 
For multi-center clinical trial, the clinical trial summary of 
each center should be signed and dated by the 
investigators of respective center, and submitted to the 
leading site after being reviewed, dated and sealed by 
the site's clinical trial administration department. 
(GCP for Medical Devices, CFDA order No.25 Article 86) 
 
Sponsor will submit the final report to NMPA  after obtaining 
it from the medical institution. 
Medtronic records and reports will be stored in secure file cabinets at Medtronic during the course 
of the study. Electronic versions of the reports will be kept on a password-protected document 
management system.  After closure of the study, all records and reports will be archived 
indefinitely 
15.7. Publication and Use of Information 
Publications based on the results of the study will follow the process outlined in the Clinical Study 
Agreement. 
. 

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15.8. Suspension or Early Termination 
15.8.1. 
Planned Study Closure 
Study Closure is a process initiated by distribution of an initial study closure letter. Study closure is 
defined as closure of a clinical study that occurs when Medtronic and/or regulatory requirements 
have been satisfied per the protocol and/or by a decision by Medtronic or regulatory authority, 
whichever occurs first. The study closure process is complete upon distribution of the Final Report 
or after final payments, whichever occurs last. Ongoing IRB oversight is required until the overall 
study closure process is complete. 
15.8.2. 
Early Termination or Suspension 
Early Termination of the study is the closure of a clinical study that occurs prior to meeting defined 
endpoints. This is possible for the whole study or a single site. Study Suspension is a temporary 
postponement of study activities related to enrollment and distribution of the product. This is 
possible for the whole study or a single site. 
Study-Wide Termination or Suspension 
Possible reasons for considering study suspension or termination of the study include but are not 
limited to: 
• 
Adverse events associated with the system or product under investigation which might 
endanger the safety or welfare of the subject 
• 
Observed/suspected performance different from the product’s design intent 
• 
Decision by Medtronic (circumstances include but are not limited to; interests of the health 
of the study subjects, continuation of the study cannot serve any scientific  purpose, 
insolvency) or regulatory body (where the study is operating under regulatory body 
authority) 
• 
Technical issues during the manufacturing process 
Investigator/Site Termination or Suspension 
Possible reasons for clinical investigator or site termination or suspension include but are not limited 
to: 
• 
Failure to obtain initial IRB approval or annual renewal of the study 
• 
Persistent non-compliance to the clinical investigation (e.g. failure to adhere to eligibility 
criteria, failure to follow subjects per the scheduled follow-ups) 
• 
Lack of enrollments 

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• 
Noncompliance to regulations and the terms of the Clinical Trial Agreement (e.g. failure to 
submit data in a timely manner, failure to follow-up on data discrepancies and monitoring 
findings in a timely manner, etc.) 
• 
IRB suspension 
• 
Fraud or fraudulent misconduct is discovered  
• 
Investigator request (e.g. no longer able to support the study) 
15.8.3. 
Procedures for Suspension or Termination 
Medtronic-Initiated 
 
• 
For deciding to suspend or terminate clinical trials, sponsor shall notify the management 
department of medical device clinical trials of all clinical trial institutions within 5 days, and 
state the rationale in written form. 
• 
Management department of medical device clinical trials in clinical trial institutions shall 
timely notify corresponding investigators and Ethics Committee. 
• 
The suspended clinical trials shall not be recommenced without the approval of Ethics 
Committee. 
• 
Upon the completion of clinical trials, sponsor shall notify local food and drug regulatory 
authority of the province, autonomous region and municipality directly under the central 
government where he locates in written form. 
• 
Upon receipt of notification of suspending or terminating clinical trials from sponsor, 
investigators shall timely notify subjects and ensure that subjects receive appropriate 
treatment and follow-up.  
• 
In the case of a study suspension, subject enrollment must stop until the suspension is lifted 
by Medtronic with the approval of Ethics Committee. 
• 
In the case of a study suspension, enrolled subjects should continue to be followed out of 
consideration of their safety, rights and welfare. 
 
Clinical Trial Institution and Investigator-Initiated 
• 
If it is required to suspend or terminate the trial as the clinical trial institution and 
investigators found that the risk outweighs the possible benefits or results have been 
obtained that suffice the judgment of the safety and effectiveness of medical device, the 
investigators shall inform the subjects, and make sure appropriate treatment and follow-up 
visits for the subjects, and meanwhile report as required with detailed written explanation 
for the suspension and termination. 

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• 
Clinical Trial Institution and Investigator shall report to the food and drug regulatory 
authorities of the provinces, autonomous regions and municipalities directly under the 
central government if necessary. 
• 
In the case of a study suspension, subjects enrolled should continue to be followed out of 
consideration of their safety, rights and welfare. 
 
EC/IRB-Initiated 
 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension within 5 business days 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance with Ethics 
• 
Committee policy or its determination that an overriding safety concern or ethical issue is 
involved 
• 
The investigator will inform his/her institution (where required per local requirements) 
• 
Upon receipt of notification of suspending or terminating clinical trials from Ethics 
Committee, investigators shall timely notify subjects and ensure that subjects receive 
appropriate treatment and follow-up.  
 
 
 

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16. Appendixes  
 
Appendix : Study Contact 
Sponsor:  
Medtronic SOFAMOR DANEK USA 
1800 Pyramid Place, Memphis, TN USA 38132. 
Local Sponsor: 
Medtronic (Shanghai) Management Co., Ltd. 
11F, Building B, No 5, Lane 255, DongYu Road, 
Pudong, Shanghai 
Clinical Operations: 
Medtronic Inc 
CHN Medtronic Core Clinical Solutions 
11F, Building B, No 5, Lane 255, DongYu Road, 
Pudong, Shanghai 
Monitoring: 
Medtronic Inc 
CHN Medtronic Core Clinical Solutions 
11F, Building B, No 5, Lane 255, DongYu Road, 
Pudong, Shanghai 
The detailed contact list will be kept separate from the CIP and provided to the Investigators. 
Medtronic will maintain an updated list. For specific contact information of the core members refee 
to the detailed list. 
For the relevant qualification documents of Medtronic refer to the EC review document package. 
 
 

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056-F275, v3.0 Clinical Investigation Plan Template 
 
 
 
 
Appendix A: Informed Consent Form 
The ICF template will be provided under a separate cover. 
 
 

Xpede Clinical Investigation Plan  
 
 
 
Version 3 17 Sep 2018 
Page 78 of 78 
 
Medtronic Confidential 
This document is electronically controlled  
 
056-F275, v3.0 Clinical Investigation Plan Template 
 
 
 
 
Version History 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
New Document 
Tristan Zhao, Clinical Research 
Sr. Manager 
Laura 
Manotta, 
EMEA 
RCC 
Principal 
Proj 
and 
Clinical 
Research Spec 
 
2.0 
• 
Updated indication for Use according to 
M708348B093E Rev C 
• 
Correction of minor typos 
Laura 
Manotta, 
EMEA 
RCC 
Principal 
Proj 
and 
Clinical 
Research Spec 
 
3.0  
• 
Update inclusion criteria: age range between 
18-80 years  
• 
Specification that the efficacy will be 
evaluated by a blinded investigator 
• 
Definition of a central image reading CoreLab 
• 
Removal of the CEC as not required by local 
regulation 
Laura Manotta, EMEA S&SS 
Principal 
Proj 
and 
Clinical 
Research Spec