A Prospective, 5-Year Global Study on MAST™ Minimally Invasive Fusion Procedures for the Treatment of the Degenerative Lumbar Spine
Conditions: Intervertebral Disc Degeneration
Sponsor: Medtronic Spinal and Biologics

 
 
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MASTERS-D 2  
Clinical Investigation Plan 
 
Version 4.0 
 22 Feb 2019 
P15-01 
 
Global Sponsor 
Medtronic Bakken Research Center BV 
Spinal and Biologics Clinical 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
 
 
Local sponsor (China) 
Local sponsor (Korea) 
Local sponsor (Latin America) 
Medtronic (Shanghai) Management Co., Ltd. 
 Floor 6-17, Building B, The New Bund World 
Trade Center Phase I, 
No 5, Lane 255, DongYu Road 
Pudong, Shanghai, P.R.China 
Medtronic Korea Ltd. 
424, Yeongdong-daero, 
Gangnam-Gu, Seoul, 135-280, 
Korea 
Medtronic Latin America HQ 
- Miami Florida 
9850 NW 41st St Ste 450 
Miami, FL 3317 
USA 
 
 

 
 
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Change History record 
 
CIP Change History 
Version 
Summary of Changes 
Author 
1.0 
Initial Release 
 
2.0 
• 
Section Approval Sheet: Will be kept separately 
• 
Section CIP SYNOPSIS: CIP synopsis has been incorporated to the CIP.  
• 
Section: A.2.3 Cages Systems: The AVILA™ Interbody Fusion Device  has been added 
• 
Sections B.1.2. Primary objective and endpoint AND B.1.3. Secondary objectives and 
endpoints (both in main CIP and in Synopsis); B.4 Study hypothesis; B.7 Sample size; and 
throughout the document: Clarification that the population is Degenerative Disc Disease 
(DDD) patients. As it is mentioned in the inclusion criteria already.  
• 
B.1.2 Primary objective and endpoint: Definition of “procedure” clarified: “In this 
prospective study design, patients will be enrolled in one of the 6 procedure groups: ALIF, 
OLIF, DLIF, PLIF, TLIF or MIDLF” 
• 
Section Rationale for selection of the secondary endpoints – Fusion: 
o 
Clarification that “If no fusion is observed during the first fusion assessment further 
fusion assessment(s) will be at the discretion of the investigator”.  
o 
Modification of fusion success definition: “If a subject shows fusion success at early 
timepoints and non-fusion at a later timepoint, the fusion status at all earlier points 
should be considered as non-fusion.” 
• 
Section Rationale for selection of the secondary endpoints - second surgery: 
o 
Terminology harmonization: intervention replaced by surgery.  
o 
Clarification in the paragraph that the second surgery will be collected as well for 
“adjacent level(s)” as already mentioned in the title. 
o 
Removal of “reoperation form” as not existing in the case report form. 
• 
Section Rationale for selection of the secondary endpoints DN4 questionnaire, (Douleur 
Neuropathique 4 (neuropathic pain)): 
o 
Full paragraph added to explain the DN4 questionnaire as well as rational and 
references 
• 
Section Additional spinal cord stimulation or pain pump: Addition of this section as 
additional measurement 
• 
Section B.3 Definitions Study Procedures: L4-L5 added in ALIF definition as these levels 
can also be treated with an ALIF procedure 
• 
Section B.5 Study design: The terminologies “Cohort”, “Pragmatic” and “patient centered 
case series” were removed in order to align with other sections. 
• 
Sections B.6 Randomization and blinding; B.7.Sample Size; E.1. Screening; E.11. Study 
deviations and CIP changes: Removal of the terminology “cohort” to align with other 
sections. 
• 
Section B.7 Sample size: Clarification added that “The amount of patients with 
spondylolisthesis versus non-spondylolisthesis will be monitored during the study. […]” 
 

 
 
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this will allow to make sure that the sample size defined in this protocol is reached in case 
high amount of non-spondylolisthesis versus spondylolisthesis patients are enrolled. 
• 
Sections B.7 Sample size AND E.9 Adverse events: References to Canada are removed as 
this country will not participate 
• 
Sections B.7 Sample size: 
o 
Correction of terminology “cohort” and replacement by “procedure”: “A minimum 
enrollment of 80 patients in each procedure (ALIF, OLIF, DLIF, PLIF, TLIF or MIDLF) is 
required.” 
o 
Addition of information on site/region enrollment limit 
o 
Latin America and Middle-Est Overview of patient enrollment has been increased to a 
maximum of 20 enrollment per site and 15 per procedure 
• 
Section(s) B.8 Number of investigation sites and study duration AND Synopsis - Patient 
Population: 
o 
Timelines adaptation: Patients “will be enrolled over a period of around 28”; The total 
duration of the study will be of approximately 88 months; Enrolment will start in 2016 
and the final follow up visit is expected in 2023. 
o 
Addition of “Depending on enrolment progress, study timelines are subject to 
change.” 
• 
Section C SUBJECT SELECTION: 
o 
Inclusion Criteria:  
o 
Inclusion of patient who are 18 years old by changing to more or equal: “Patient is ≥ 
18 years of age” 
o 
Clarification that: “For a double level instrumented fusion, the same procedure must 
be used for both levels” 
o 
Exclusion Criteria:  
o 
Clarification that patient participating to a concurrent clinical study should not be 
enrolled if “that may confound study results” 
• 
Section D.2.1 EC/IRB approval: Clarification that “when the sponsor is responsible for EC 
submission, a written documentation from the sponsor is required. “ 
• 
Section D.2.3 Revisions in Patient Information and Informed Consent Form: Clarification 
that “in case the revised Informed Consent has no impact on previously enrolled patients, 
the Informed Consent won’t need to be re-signed by already enrolled patients.” 
• 
Section D.3 Regulatory compliance: Addition of “If any action is taken by a EC/IRB with 
respect to the investigation, the information will be forwarded to the sponsor.” 
• 
Table 2: Description of Procedures and Assessments at different time intervals: 
o 
Addition of “DN4 for back and DN4 for leg” at Baseline, 3m, 1 year 
o 
Addition of “As DN4 questionnaire has been added in the CIP amendment 2.0, the 
patients who were enrolled under CIP version 1.0 will NOT complete the DN4 
retrospectively but will complete the DN4 questionnaires for any upcoming follow up 
visits.” 
• 
Section E.1 Screening: Clarification of Subject Identification & Enrollment Log maintenance 
• 
Section E.3 Baseline procedures: Addition of “The identification of neuropathic pain will 
be assessed by the DN4 questionnaire in the back and in the leg.” 
• 
Section E.4 Implant or procedure aspects: Clarification “Patient […] might not be operated 
to treat the degenerative lumbar spine or might have a different procedure for other 
reasons” 
• 
Section E.6 Follow up requirements: Addition of “The identification of neuropathic pain 
will be assessed by the DN4 questionnaire in the back and in the leg at 3 and 12 months 
follow up.” 

 
 
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• 
Sections E.7 Data collection requirements AND F.1.2. Data collection: Correction: patient 
satisfaction removed (not collected in this study) 
• 
Table 3: Summary of scheduled procedures and assessments AND Synopsis Table 1: 
Summary of scheduled procedures and assessments:  Addition of DN4 in the back and 
DN4 in the leg at Baseline, 3 months and 1 year 
• 
Section E.8 Source documents: Addition of “DN4 in the back and DN4 in the leg” 
• 
Section E.9.1.1 Definition/classification - Related to the disease: Definitions changed in 
order to be aligned with MEDDEV 2.7/3 definitions 
• 
Section E.9.1.2 Recording and reporting of Adverse Events: Clarification of the reporting 
• 
Section E.9.1.3 Recording and reporting of Device Deficiencies: Clarification of the 
reporting 
• 
Section E.9.1.5 Reporting of product complaints: This section has been reworded entirely 
to be clearer for the site 
• 
Section E.9.3 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact 
details: 
o 
Section has been added to clarify the actions needed in case CRF not accessible.  
o 
Emergency contact details updated 
• 
Section E.10 Subject accountability: 
o 
Addition of “Patient did not undergo the instrumented lumbar fusion as defined in 
this protocol” 
o 
Addition of “Subjects withdrawn from the study will only be replaced when patients 
did not undergo the instrumented lumbar interbody fusion with posterior fixation as 
defined in this protocol if the enrollment is still open. In that case only, these patients 
will not contribute to the site and region specific enrollment limits nor to the 
maximum amount of patient enrollments per procedure.” 
• 
Section E.11 Study deviations and CIP changes AND Table 6 Deviation - Actions overview 
table: Addition of deviations that will be tracked in the eCRF 
• 
Section F.1.4 Data review and processing: Clarification of the Data electronic storage 
maintenanceSection F.2.2 Interim Monitoring visits: the percentage of data monitored is 
replaced by level of monitoring for correctness. 
• 
Section G.1 Analysis of clinical data: Clarification of Analysis data set 
• 
Section G.1.2 Analysis of Secondary Endpoints: 
o 
Change in Fusion analysis: “Time-to-event-analysis will be conducted for fusion 
success” 
o 
Addition of DN4 analysis 
• 
Section G.2 Publication Policy: Addition of ClinicalTrials.Gov reference 
• 
Throughout the documents: Duplications and typos have been respectively deleted and 
corrected. Furthermore the abbreviations were harmonized 
• 
Section REFERENCES: This section has been updated 
• 
Section K APPENDICES: Clarification that List of sponsor staff and List of Advisory 
Committee Members will be kept separately 
3.0 
• 
Minor textual changes throughout the Clinical Investigation Plan 
• 
Incorporated all requirements of CIP Region Specific Addendum: Asia Pacific Version 2.0, 
25 Oct 2016 in this Masters-D2 CIP version 3.0. 
• 
Section title page: added local sponsors for China (new address), Korea and Latin America 
• 
Section CIP SYNOPSIS:  
o 
Timelines have been adjusted to reflect the current estimated timelines. 
 

 
 
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o 
Inclusion criteria: Reference to section Medical Devices has been corrected to 
refer to section Device information. 
o 
Clarified that Medtronic BRC is the Global Sponsor 
• 
B.1.2 Primary objective and endpoint: Moved primary endpoint after objective to have a 
more logical order. Removed duplicate text in section rationale for primary endpoint 
selection. 
• 
B.5 Study design:  
o 
An email will be sent to the participating sites to inform the investigators (not the 
patients as initially indicated) when the enrollment for a specific procedure is 
complete. 
o 
Refusal of study participation as well as enrollment into the study will be 
recorded for statistical purposes from the investigators on the screening log. This 
sentence was removed because no statistical analysis will be performed on the 
screening log. 
• 
B.6 Randomization and blinding: Moved ODI information to section B.5 which describes 
measures to avoid bias. Clarified that blinding is not applicable in this study. 
• 
B.7 Sample size:  
o 
Aligned regions with synopsis by removing specifications of individual countries 
o 
Restructured the section about enrollments.  
o 
Included information from Asia Pacific addendum with regard to enrollment 
limits. Adjusted enrollment max per procedure for Korea to 20. Included a 
potential additional site for China and Europe to align with the estimate of 38 
sites. 
o 
Added : patient enrolment may be stopped when the required sample size for 
the primary endpoint has been reached. 
o 
Minimum enrolment of 80 patients in each procedure (ALIF, OLIF, DLIF, PLIF, TLIF 
or MIDLF) reduced to 40 and added sentence that study will aim to balance the 
subjects equally between the procedures.  
o 
Adjusted enrollment maximum per site for Europe to 40 patients and increased 
the enrollment maximum per procedure for each site in Europe, Latin America 
and Middle East. 
o 
Clarified that the limits in table 1 may be subject to change during the course of 
the study and will be communicated as appropriate to the investigators and 
EC/IRB, if required.  
o 
Added note to allow for change in enrollment limits per procedure to have a 
better distribution of procedures amongst the sites and regions.  
• 
B.8 Number of investigation sites and study duration:  Timelines have been adjusted to 
reflect the current estimated timelines. 
• 
C.1 Inclusion and exclusion criteria: Inclusion criteria: Reference to section Medical 
Devices has been corrected to refer to section Device information. 
• 
D.2.2 Informed consent process: Clarified that “the process must be documented” before 
any clinical study related activity takes place.  
• 
D.2.4 Data Release Consent process: Clarified that “the process must be documented” 
prior to releasing any personal information of the patient. 

 
 
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• 
D.3 Regulatory compliance: Clarified that EC/IRB may also impose additional 
requirements. Removed reference to APAC CIP addendum since all requirements are 
captured in this version of the CIP.  
• 
D.4 Training requirements: Use of data collection tools ( CRF training updated to EDC 
training for correctness) 
• 
E.7 Data Collection requirements: 4 weeks (± 2 weeks) visit changed from mandatory 
hospital visit to potential phone visit. 
• 
E.9 Adverse events: References to China safety and vigilance reporting requirements are 
added from the Asia Pacific Addendum. The Korea safety and vigilance reporting 
requirements are updated to reflect the new requirements. 
• 
E.9.1.1 Definition/classification: References added to Korea GCP and UADE definition 
included from Asia Pacific Addendum.  
• 
E.9.1.4: Adverse Event and Device Deficiency review process: Table 5 reporting 
requirements added for Korea. 
• 
E.9.1.5: Removed reporting of product complaints according to local Product Complaint 
Handling SOP as the investigators are not trained on Medtronic procedures so they wil 
only report via the regular channels for market-released products. 
• 
F.2.2 Interim Monitoring Visits: Updated source data verification language to align with 
the monitoring plan. Added certified copy definition. 
• 
G.1.4 Interim Analysis: Section updated to provide more clarification on the interim 
analysis.  
• 
H.4.1 Insurance: Replaced Medtronic Plc. With Medtronic after advice from legal.  
 
4.0 
• 
B.7 Sample size 
Equivalence range was redefined from -7.5, 7.5 points to -10, 10 points ODI improvement 
at 3 months between anterolateral and posterior group 
Due to the change in equivalence range the estimated sample size per group 
(anterolateral procedures versus posterior procedures) was updated from 122 to 70. The 
estimated total sample size for spondylolisthesis patients with DDD was decreased from 
244 to 140 
As from the MASTERS-D study it is known that approximately 50% of the patients with 
degenerative disc disease have spondylolisthesis ≥ grade I. Hence the required total 
sample size was also changes from 244/0.5=488 to 140/0.5 = 280.  
The anticipated patients to be enrolled in the study was also changed from 560 to 350. 
Minimum enrollment of 40 patients was changed to 20 patients in order to accommodate 
also the lower sample size of the study. 
In Table 1: “Overview of patient enrollment limits in Europe, Latin America, Middle East 
and Asia Pacific per site and per procedure. “, the Middle East was removed as 
participating region and estimated number of sites corrected for EU and China. 
 
 

 
 
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• 
B.8 Number of investigation sites and study duration: Number of estimated patients 
updated per section B.7 and Middle East was removed as participating region  
• 
G.1.1 Analysis of Primary Endpoint: Equivalence range update  from (-7.5, 7.5) points to (-
10, 10)  
• 
E.7. Data collection requirements - Table 1: Summary of scheduled procedures and 
assessments  - lay out reformatted. 
• 
H.3.5 Record retention : added information for Europe in order to comply with EU MDR: 
The documentation shall be kept for a period of at least 15 years after the clinical 
investigation with the device in question has ended  
• 
General comment: 
This CIP amendment (Version 4.0) is related to an increase of equivalence range and the 
impact is that number of patients enrolled into the the study is reduced from about 560 to 
approximately 350 patients, Even though the number of patients enrolled in the study 
worldwide is mentioned in the Patient Informed Consent/Patient Data Release form it has 
been decided not to reconsent the patients unless if this is requested by the IRB/EC. 
Rationale for not reconsenting patients is the following: 
- 
The amendment does not include new information that might affect patients’ 
health, welfare and willingness to continue participation in the study. 
- 
The amendment does not change assessments for the patients already included 
or to be included in this study. 
- 
It is not expected that a decrease in sample size will cause already enrolled 
patients to change their mind about study participation 
- 
In case new information becomes available from this or other studies that may 
affect the patient’s health, welfare, or willingness to stay in this study, the 
patient’s will be informed about it as soon as possible. 
For those sites were enrollments are still expected after approval of CIP version 4.0 a site 
specific consent will be created and submitted for approval to the ethics committee 
indicating the correct number of expected enrollments. Since the change is only related to 
the number of pts enrolled in this study, no new master template nor country specific 
templates will be prepared as no other changes will be made to the already previously 
approved PIC/DRF. 
 
 

 
 
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TABLE OF CONTENTS 
 
CIP SYNOPSIS ......................................................................................................................................................... 12 
TITLE AND STUDY IDENTIFICATION NUMBER ........................................................................................................ 15 
A 
GENERAL INFORMATION ............................................................................................................................ 15 
A.1 
Introduction .................................................................................................................................... 15 
 Study Rationale .................................................................................................................... 15 
 Costs/Health Economics ...................................................................................................... 16 
 Literature Update ................................................................................................................. 16 
 Risks-Benefits from a Literature perspective ....................................................................... 17 
A.2 
Device information .......................................................................................................................... 18 
 Posterior Fixation (Stabilization) Systems ............................................................................ 19 
 Access Systems..................................................................................................................... 19 
 Cages Systems ...................................................................................................................... 20 
 Plates .................................................................................................................................... 20 
 Bone Grafts and Substitutes ................................................................................................ 20 
B 
STUDY PLAN ................................................................................................................................................ 21 
B.1 
Study Objectives and Clinical Endpoints ......................................................................................... 21 
 Study Objectives .................................................................................................................. 21 
The MASTERS-D 2 clinical study aims: ............................................................................................. 21 
 Primary objective and endpoint........................................................................................... 21 
 Secondary objectives and endpoints ................................................................................... 22 
 Additional Measurements ................................................................................................... 24 
B.2 
Study Population ............................................................................................................................. 25 
B.3 
Definitions Study Procedures .......................................................................................................... 26 
B.4 
Study hypothesis ............................................................................................................................. 26 
B.5 
Study design .................................................................................................................................... 27 
B.6 
Randomization and blinding............................................................................................................ 28 
B.7 
Sample size ...................................................................................................................................... 28 
B.8 
Number of investigation sites and study duration .......................................................................... 29 
C 
SUBJECT SELECTION .................................................................................................................................... 29 
C.1 
Inclusion and exclusion criteria ....................................................................................................... 29 
D 
STUDY PREPARATION PROCEDURES........................................................................................................... 30 
D.1 
Investigator/Investigation site selection ......................................................................................... 30 
 Clinical Investigation Agreement ......................................................................................... 30 
 Curriculum Vitae .................................................................................................................. 31 
D.2 
Ethics ............................................................................................................................................... 31 
 EC/IRB approval ................................................................................................................... 31 
 Informed consent process ................................................................................................... 32 
 Revisions in Patient Information and Informed Consent Form ........................................... 32 
 Data Release Consent process ............................................................................................. 33 

 
 
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 Regulatory notification / approval ....................................................................................... 33 
D.3 
Regulatory compliance .................................................................................................................... 33 
D.4 
Training requirements ..................................................................................................................... 34 
D.5 
Site readiness .................................................................................................................................. 34 
D.6 
Study materials and study-specific equipment ............................................................................... 34 
E 
STUDY METHODS ........................................................................................................................................ 34 
E.1 
Screening ......................................................................................................................................... 36 
E.2 
Point of enrollment ......................................................................................................................... 36 
E.3 
Baseline procedures ........................................................................................................................ 36 
E.4 
Implant or procedure aspects ......................................................................................................... 36 
E.5 
Post Procedure to Discharge ........................................................................................................... 37 
E.6 
Follow up requirements. ................................................................................................................. 37 
E.7 
Data collection requirements .......................................................................................................... 38 
E.8 
Source documents ........................................................................................................................... 39 
E.9 
Adverse events ................................................................................................................................ 39 
 Adverse Events and Device Deficiencies .............................................................................. 40 
E.9.1.1 
Definition/classification ...................................................................................... 40 
E.9.1.2 
Recording and reporting of Adverse Events ....................................................... 43 
E.9.1.3 
Recording and reporting of Device Deficiencies ................................................. 43 
E.9.1.4 
Adverse Event and Device Deficiency review process ........................................ 44 
E.9.1.5 
Reporting of product complaints ........................................................................ 47 
 Adverse Event Advisory Committee..................................................................................... 47 
 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact details ...... 47 
E.10 
Subject accountability ..................................................................................................................... 48 
E.11 
Study deviations and CIP changes ................................................................................................... 48 
 Request for approval of study deviations ............................................................................ 49 
 Reporting requirements for study deviations ...................................................................... 50 
 Amendments to the Clinical Investigation Plan ................................................................... 50 
F 
QUALITY CONTROL PROCEDURES............................................................................................................... 50 
F.1 
Procedures for database management ........................................................................................... 50 
 Data collection ..................................................................................................................... 50 
 Source data to be directly recorded on the Case Report Forms .......................................... 50 
 Time windows for completion and submission of Case Report Forms ................................ 50 
 Data review and processing ................................................................................................. 51 
F.2 
Monitoring procedures ................................................................................................................... 51 
 Site Initiation Visits .............................................................................................................. 51 
 Interim Monitoring Visits ..................................................................................................... 51 
 Close out visits (COV) ........................................................................................................... 52 
 Accessibility of investigation site staff and study materials................................................. 52 
 Audits and investigation site inspections ............................................................................. 52 
F.3 
Study suspension or early termination ........................................................................................... 53 

 
 
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 Early study suspension or termination ................................................................................ 53 
 Early investigation site suspension or termination .............................................................. 53 
 Subject follow-up in case of termination ............................................................................. 53 
F.4 
Study close out ................................................................................................................................ 53 
G 
DATA ANALYSIS AND REPORTING ............................................................................................................... 53 
G.1 
Analysis of clinical data ................................................................................................................... 53 
 Analysis of Primary Endpoint ............................................................................................... 53 
 Analysis of Secondary Endpoints ......................................................................................... 53 
 Additional Data Analysis ...................................................................................................... 54 
 Interim Analysis .................................................................................................................... 55 
G.2 
Publication Policy ............................................................................................................................ 55 
H 
MANAGEMENT ........................................................................................................................................... 56 
H.1 
Study staff ....................................................................................................................................... 56 
H.2 
Advisory committees ....................................................................................................................... 56 
 Advisory Committee ............................................................................................................ 56 
 Data Monitoring Committee ................................................................................................ 56 
 Publication Committee ........................................................................................................ 56 
H.3 
Records and reports ........................................................................................................................ 56 
 Investigator records ............................................................................................................. 56 
 Investigator reporting responsibilities ................................................................................. 57 
 Sponsor records ................................................................................................................... 57 
 Sponsor reporting responsibilities ....................................................................................... 58 
 Record retention .................................................................................................................. 58 
H.4 
Miscellaneous .................................................................................................................................. 58 
 Insurance .............................................................................................................................. 58 
 Subject compensation and indemnification ........................................................................ 59 
 Subject confidentiality ......................................................................................................... 59 
I 
RISKS AND BENEFITS ................................................................................................................................... 59 
I.1 
Anticipated Clinical Benefits ............................................................................................................ 59 
I.2 
Risks ................................................................................................................................................. 59 
J 
REFERENCES ............................................................................................................................................... 60 
K 
APPENDICES ................................................................................................................................................ 65 
K.1 
Names and addresses...................................................................................................................... 65 
 List of contact persons ......................................................................................................... 65 
K.2 
Case Report Forms .......................................................................................................................... 65 
K.3 
Sample Investigator Agreement ...................................................................................................... 65 
K.4 
Abbreviations .................................................................................................................................. 65 
K.5 
Definitions ....................................................................................................................................... 66 
K.6 
Sample Statement that no Ethics Committee approval is required ................................................ 67 
 
 

 
 
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TABLE OVERVIEW 
 
 
Table 1: Overview of patient enrollment limits in Europe, Latin America, Middle East and Asia Pacific per site and per 
procedure. .......................................................................................................................................................................... 29 
Table 2: Description of Procedures and Assessments at different time intervals .............................................................. 34 
Table 3: Summary of scheduled procedures and assessments .......................................................................................... 38 
Table 4: Adverse Events Definitions ................................................................................................................................... 40 
Table 5: Adverse Event reporting requirements................................................................................................................. 44 
Table 6 Deviation - Actions overview table ........................................................................................................................ 49 
Table 7: Investigator Reporting Responsibilities Overview ................................................................................................ 57 
Table 8: Sponsor Reporting Responsibilities Overview ...................................................................................................... 58 
Table 9: Definitions ............................................................................................................................................................. 66 

 
 
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CIP SYNOPSIS 
Name of Trial 
MASTERS-D 2 
Title of Trial 
A Prospective, 5-Year, Global Study on MAST™ Minimally Invasive Fusion Procedures for the 
Treatment of the Degenerative Lumbar Spine.  
Identification # 
P15-01 
Purpose 
 
To evaluate the effectiveness of MAST techniques for anterior/lateral and posterior 
approaches in patients with spondylolisthesis (≥ grade I).  
 
To assess how single or double level MAST fusion procedures PLIF, TLIF, DLIF, OLIF, ALIF, or 
MIDLF are used in surgical practice and to describe long-term safety and effectiveness  in 
a broad patient population of patients with degenerative lumbar disc disease .  
Design 
Prospective, Global (multi center), Post Market Release (PMR) Study  
Name of product 
Medtronic CD Horizon® Spinal Systems.  
CD HORIZON® Spinal System consists of a variety of rods, hooks, screws, plates, and other 
connecting components used to build a spinal construct. Instrumentation is also available to 
facilitate implantation of these components. 
Primary Objective 
& Endpoint 
To demonstrate that Degenerative Disc Disease (DDD) patients operated for spondylolisthesis 
fare equally well regardless of the surgical procedure (anterolateral or posterior) performed as 
measured by the improvement of Oswestry Disability Index (ODI) at 3 months as compared to 
baseline.  
Endpoint: Improvement of disability at 3 months post-operatively as compared to baseline. 
Secondary 
Objectives & 
Endpoints 
 
To evaluate whether DDD patients without spondylolisthesis fare equally well regardless 
of the surgical procedure (anterolateral or posterior) performed, as measured by 
Oswestry Disability Index (ODI) at 3 months 
 
To observe and document clinical and radiological outcomes through 5 year follow-up 
(except for ODI at 3 months) 
- 
Improvement of ODI as compared to baseline 
- 
Improvement of VAS back- and leg pain intensity as compared to baseline 
- 
Improvement of EQ-5D as compared to baseline 
- 
Neurological success 
- 
Fusion success  
- 
Secondary Surgeries at index and/or adjacent level(s)  
- 
Adverse Events 
 
To observe and document the patients’ short term recovery after surgery 
- 
Time needed for first ambulation: Days needed for patient to get out of bed and 
ambulate with or without assistance 
- 
Surgery Recovery Day: Days after the surgery, fulfilling following criteria: 
 No need for intravenous infusion of analgesic drugs 
 No ongoing surgery related adverse events impeding discharge  
 No need for nursing care 
 
To document health resources consumption and perform economic analyses. 
 
To observe and document the patient profile when choosing a particular minimally 
invasive fusion procedure. 
 
 

 
 
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Patient 
Population  
Approximately 350 patients suffering from lumbar degenerative disc disease (DDD) will be 
enrolled over a period of around 4 years in approximately 30 sites located in Europe, Middle 
East, Latin America and Asia Pacific. As the patients will be followed during a period of 5 years 
after the surgical procedure, the total duration of the study will be of approximately 9 years. 
Enrollment has started in 2016 and the final follow up visit is expected in 2025.   
Treatment 
A single or double level instrumented fusion using minimally invasive PLIF, TLIF, MIDLF, DLIF, 
OLIF, ALIF procedures for the treatment of the degenerative lumbar spine. The use of a 
posterior fixation system is mandatory in this study and will be either mini-open and/or 
percutaneous. 
Inclusion 
Criteria 
 
Patient is ≥ 18 years of age (or minimum age as required by local regulations) 
 
Patient has degenerative disc disease and an indication for a single or double level 
instrumented lumbar fusion for the treatment 
 
Patient agrees to participate in the study and is able to sign the Data Release 
Form/Informed Consent 
 
The procedure planned for the patient complies with the labeling of the Devices that may 
be used in the surgical procedure as described in the section Device information of this 
Clinical Investigation Plan 
 
Patient is planned to be submitted to a minimally invasive fusion procedure using a 
posterior (PLIF, TLIF, MIDLF) or anterolateral (OLIF, ALIF, DLIF) technique * 
 
The patient is willing and is able to perform study procedures and required follow-up 
visits. 
* For a double level instrumented fusion, the same procedure must be used for both levels. 
Exclusion 
Criteria 
 
Patient that has already undergone a lumbar fusion surgery 
 
Patient that has already undergone open lumbar surgery other than standard 
decompression surgery 
 
Indications for the procedure other than degenerative spine disease like: Osteoporotic 
vertebral fractures, Spine trauma fractures or Spine tumor 
 
Illiterate or vulnerable patients (e.g. minors, participants incapable of judgment or 
participants under tutelage)   
 
Concurrent participation in another clinical study that may confound study results. 
Clinical 
Procedures and 
Assessments 
Assessments will be done pre-operative, during surgical procedure and hospital stay and post-
operative at 1, 3 months, 1, 2, 3, 4 and 5 year follow up. See table 1 (below) 
Global Sponsor 
Medtronic Bakken Research Center (Maastricht, The Netherlands). 
 
         
 
 

 
 
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 Table 1: Summary of scheduled procedures and assessments  
 
    (1) Patient Informed Consent must be obtained prior to performing any study specific procedure  
    (2) Day ‘0’ (D0) is the day of the surgery, D1 is the first day after surgery, D2 the second and so on. 
    (3) SRD = Surgery Recovery Day; DIS = Day of Discharge 
    (4) VAS Intensity scores for Back and Leg pains. 
    (5) CT scan or X-Rays at 1 year follow up. If no fusion is observed at 1 year follow-up, it will be at the discretion of the investigator to 
follow up if fusion can be observed (only if standard of care at the site).  
    
    (6) Optional only if it is routine practice (standard of care) at the site  
 
 
 
Baseline 
Day of 
Surgery (D0) (2) 
Hospital 
Stay and 
Discharge 
(3) 
Follow up assessments 
D2 
SRD 
DIS 
4(±2)week 
 
3(-1.5/+3)month 
   1 year            
(±6 months) 
        2 year       
(±6 months)  
3 year        
(±6 months) 
4 year         
(±6 months) 
5 year        
(±6 months) 
Data Release Form  OR 
Informed Consent Form 
X 
(1) 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Surgery Indication 
X 
 
 
 
 
 
 
 
 
 
 
 
Pain medication 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Imaging (X-Ray, MRI and/or CT Scan) 
X 
 
 
 
 
 
 
 
 
 
 
 
VAS (4) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ODI 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
EQ-5D 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Neuropathic pain: DN4 in the back and 
DN4 in the leg 
X 
 
 
 
 
 
X 
X 
 
 
 
 
Work status 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Rehabilitation Program 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Neurological status 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X-Ray or CT Scan (5) 
 
 
 
 
 
 
 
X 
(X) 
(X) 
(X) 
(X) 
Sagittal Balance(6) 
(X) 
 
 
 
 
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
Surgery and hospital data 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
 
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 TITLE AND STUDY IDENTIFICATION NUMBER 
Study identification number:  
P15-01 
Study name: 
MASTERS-D 2 
Study Title: 
A Prospective, 5-Year Global Study on MASTTM Minimally Invasive Fusion 
Procedures for the Treatment of the Degenerative Lumbar Spine. 
A GENERAL INFORMATION 
A.1 Introduction 
 Study Rationale 
 
The basic tenet of minimally invasive spine surgery (MIS) and MAST™- (Minimal Access Surgical Technologies) is 
to effectively treat patients with the most reliable technique while minimizing tissue trauma. The advantages of 
the minimally invasive techniques in patients with degenerative disc disorders are low morbidity, shorter 
hospitalization time, less blood loss, less muscle damage, less narcotic use, quicker entry to physical therapy and 
more rapid recovery and return to work/sports (1-3). However, it is generally considered that there is a need for 
monitored clinical studies with longer (5 years) follow-up (FU) due to the following aspects: 1) outcomes of MAST™ 
lumbar fusion techniques at long-term FU (> 2 years), in a larger patient population (> 300 patients) are still poorly 
documented; 2) there is an increased interest for cost-effectiveness data (4); 3) clinical and health economic 
benefits of the lumbar fusion may be apparent several years following the operation (5-7); FU beyond 2 years has 
been argued to be essential to formulate meaningful recommendations regarding the cost-effectiveness of lumbar 
fusion over non-fusion treatments (5); 4) FU for rare adverse events may require a longer (> 2 years) FU period 
(8). A Prospective, Long Term, Pragmatic Multicenter Post Market Release Study on MASTTM Fusion Procedures 
for the Treatment of the Degenerative Lumbar Spine (MASTERS-D, NCT01143324) was performed to observe and 
document standard of care surgical practice and to evaluate patient’s outcomes up to 12 months FU. 
Spondylolisthesis (52.8%), stenosis (71.4%), and disc pathology (93.7%) were the most common preoperative 
degenerative lumbar pathologies. All surgeries were performed by experienced physicians. The majority of the 
patients were treated via a minimally invasive transforaminal lumbar interbody fusion (TLIF) approach, at one- 
(83%) and two-levels (17%), respectively (9). The results of the study on safety and effectiveness of MAST™ from 
4 weeks up to 1-year FU showed low perioperative morbidity, early clinical recovery, improvements in Patient 
Reported Outcomes (PRO), high patient satisfaction and low complication rates.  
The results of the initial MASTERS-D study generates a platform of interest for a new study including more MAST™ 
approaches for lumbar interbody fusion (LIF), and with a longer FU (up to 5 years): the MASTERS-D 2 study.  
This new study aims to observe and understand the standard-of-care surgical practice, safety and effectiveness 
and evaluate patient’s short and long-term outcome data, following a MAST™ single- or double level fusion 
procedure using a posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), direct 
lateral lumbar interbody fusion (DLIF), oblique lumbar interbody fusion (OLIF), anterior lumbar interbody fusion 
(ALIF), or midline lumbar fusion (MIDLF) procedure in broad patient population of subjects with degenerative 
lumbar disc disease (DDD) with or without spondylolisthesis and/or stenosis. A lumbar interbody fusion in 
symptomatic patients can typically be performed by accessing the injured spine disc(s) either by an anterolateral 
(ALIF, OLIF, DLIF) or posterior (PLIF, TLIF, MIDLF) approach. The anterolateral procedures allow indirect 
decompression of the affected neural spinal structures while the posterior fusion procedures could allow direct 
decompressing (by tissue removal) of the neural spinal structures.  
 

 
 
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The results of the MASTERS-D 2 study are expected to contribute to better understanding of the different 
minimally invasive MAST™ procedures regarding patient pathology, surgical exposure and expected safety and 
clinical outcomes, from a short (intra- and peri-operative) to a long-term FU post-operatively, from the standard-
of-care perspective. 
 Costs/Health Economics  
The benefits of MIS techniques (smaller scars, diminished local pain, reduced blood loss, reduced post-operative 
wound pain, shorter hospital stay) were weighed against possible drawbacks, such as reduced orientation, steep 
learning curve, increased radiation exposure, dependency on technology, cost(10), and it was argued that 
comparative studies could convey a more realistic appreciation. However, the evidence concerning the economic 
value of the MIS surgery compared to open techniques is still scarce. Most of the data is provided by US studies, 
and concerns TLIF or PLIF surgical approaches. 
Anderson et al. reviewed available literature, reporting outcome assessment and economic value for minimally 
invasive muscle-splitting and percutaneous surgical procedures, such as DLIF(XLIF), and ALIF(11). It was concluded 
that, regardless of the approach, parameters such as reduction in blood loss, surgical site infection, hospitalization 
costs, decreased pain, less soft tissue damage, decreased postoperative narcotics use, and quicker recovery all 
developed more favorable with MIS when compared with open procedures after two years.  
Wang et al. performed a retrospective, nation wide, institutional data-base review of US data on 6106 (1667 MIS 
and 4439 open) inpatient hospital records from the Premier Perspective database (2002 to 2009), including 
patients who underwent a posterior lumbar fusion with interbody cage placement, to determine if minimally 
invasive interbody fusion is associated with cost savings when compared with open surgery (12). It was concluded 
that the majority of cost savings from MIS surgery were due to more rapid mobilization and discharge, as well as 
a reduction in outliers with extended hospitalizations. MIS lumbar interbody fusion also resulted in a statistically 
significant reduction in length of hospital stay and a reduction in total hospital costs with 2-level surgery after 
adjusting for significant covariates (age, sex, race, hospital geography and setting, payor, and comorbidities) (12). 
Parker et al. found that MIS vs. open TLIF was associated with a decreased reported incidence of surgical site 
infection from 10 MIS TLIF cohorts (362 patients) and 20 open TLIF cohorts (1,133 patients), suggesting that MIS 
could be valuable in reducing hospital costs associated with spine care (13). MIS TLIF also resulted in reduced 
operative blood loss, shorter hospital stay and decreased 2-year cost, and accelerated return to work (14). Thus, 
MIS TLIF may represent a valuable and cost-saving advancement from a societal and hospital perspective.  
Finally, a retrospective cohort comparison between MIS and open TLIF was performed to assess duration of 
narcotic use and return to work, long-term pain, disability, and quality of life (QOL) for MIS TLIF versus open TLIF 
(15). Both MIS and open TLIF provided long-term improvement in pain, disability, and QOL (EQ5D) in patients with 
back and leg pain from grade I degenerative spondylolisthesis. However, MIS TLIF allowed shorter hospital stay, 
reduced postoperative narcotic use, and accelerated return to work, reducing direct medical costs as well as 
indirect costs due to lost work productivity associated with TLIF procedures (15). 
 Literature Update 
A literature review performed on December 11th, 2011 provided a comprehensive status of available relevant 
clinical evidence for minimally invasive spine fusion for degenerative diseases (data on file)(16). In total, a number 
of 971 patients were treated with minimally invasive surgical techniques for a 1-2 level fusion. Consistently 
through the assessed studies, the short-term advantages of MIS versus open surgery were confirmed, in terms of 
blood loss, time to ambulation, and hospital stay, while operation time and radiation exposure time could be 
higher. Yet, clinical outcomes, complication rates and fusion rates were similar. The MIS techniques allowed 
significantly lower infection rates compared to their open counterparts. It was concluded that further clinical and 
economic studies, were needed to provide additional information on the long-term clinical evidence for the 
MAST™ techniques(16).  
A second literature update was performed at July 28th, 2014 by consulting the PUBMED database, for literature 
published after December 2011. The search generated 12 hits, of which four were retained for further analysis. 
Additionally, a search in the PUBMED database for articles specifically referring to the OLIF technique generated 

 
 
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three hits, of which one(17) reported only on pre-clinical data and was not further assessed. Several systematic 
reviews reporting on different MIS techniques were also considered for the literature update. Thus, a systematic 
review(3) was performed to determine whether MIS or open PLIF results in (1) better perioperative parameters, 
including blood loss, operative times, and length of hospital stay; (2) improved patient-reported outcome scores; 
(3) improved disc distraction; and (4) decreased frequency of reoperation and complications when compared with 
open PLIF procedures. It was concluded that MIS PLIF might lead to better perioperative parameters.  
A meta-analysis based on 11 current randomized and non-randomized studies was undertaken by Zang et al. to 
assess MIS versus open TLIF(2). The pooled data on a total of 785 patients showed that MIS TLIF was associated 
with less blood loss, shorter hospital stay and a trend of better functional outcomes when compared with open 
TLIF. MIS TLIF significantly increased the intraoperative X-ray exposure. Both techniques had similar operative 
time, complication rate, and re-operation rate. A quantitative meta-analysis was conducted on published studies 
reporting fusion rates after open or MIS/mini-open single or multi-level TLIF procedures for the treatment of 
degenerative disease including stenosis with spondylolisthesis and degenerative disc disease(18). Twenty-three 
articles were identified which fit the inclusion criteria. In each of the 23 studies, TLIF was performed with pedicle 
fixation and fusion was evaluated using radiograph or computed tomography scan at minimum 6-month FU. 
Overall, the studies included 1,028 patients, of which 46.8% were female. The mean age of all patients was 49.7 
years (range, 38-64.9 years), and the mean FU interval for assessment of fusion was 26.6 months (range, 6-46 
months). The usage of recombinant bone morphologic protein was higher in the MIS TLIF group (50% vs. 12%). 
Mean fusion rate from 16 studies (716 patients) of open TLIF was 90.9%, whereas mean fusion rate from 8 studies 
(312 patients) of MIS TLIF was 94.8%. Complication rate was 12.6% and 7.5% for open and MIS TLIF, respectively. 
There were no controlled comparisons between open and MIS TLIF. It was concluded that the fusion rates for both 
open and MIS TLIF were relatively high and had similar ranges. Complication rates were also similar, with a trend 
towards MIS TLIF having a lower rate. The analysis provided clear benchmarks for fusion rates in open and MIS 
TLIF procedures for spine surgeons. 
A retrospective study(19), including 179 patients receiving an OLIF procedure, performed at a single institution, 
with a FU time of 6 weeks-9 months discovered that the OLIF technique carried the same rate and risk for 
complications as the traditional anterior approach. It was concluded that OLIF can be performed easily and safely 
in lumbar spine from L2 to L5, and at L1-2 for selected cases, up three levels (via a “sliding window” through the 
abdominal muscles). Finally, the authors highlighted the need of a prospective study to compare the OLIF 
technique to the traditional anterior retroperitoneal approach. 
 Risks-Benefits from a Literature perspective 
The primary objective of lumbar surgery in patients with spondylolisthesis and stenosis is to decompress the neural 
elements, as the patients will present symptoms such as neurogenic claudication, radiculopathy and/or low back 
pain(20). The available evidence contains generally a heterogeneous cohort of subjects, often combining patients 
with and without spondylolisthesis, treated by a variety of surgical techniques, limiting fusions to patients with 
instability(21). Lumbar fusion was considered appropriate to stabilize the spine in patients diagnosed with 
spondylolisthesis with stenosis, to avoid further misalignment, recurrence of pain and/or neurological 
complaints(22). For the stenosis patients that do not improve with conservative care, the role of fusion in the 
absence of degenerative processes was uncertain(21). 
It was documented that the most common patient complications after decompression for lumbar spinal stenosis 
were per-operative dural lesions (23). The overall incidence for dural lesions was 7.4%, and high age, previous 
surgery and smoking were risk factors for sustaining a lesion. However, at 1 year FU the outcome was not affected 
negatively by these factors (23). Surgery for lumbar spinal stenosis in obese patients led to a clinically important 
(>10%) weight loss in 8% of the patients. The weight loss was not related to changes in patient-related outcomes 
(23). In the early 2000, the first reports were published on MIS TLIF with percutaneous pedicle screw fixation via 
tubular retractors, developed to avoid surgery-related lesions to the paraspinous muscle (20, 24, 25). It is well-
documented and generally accepted that MIS techniques result in less blood loss, less post-operative pain, shorter 
hospital stay, faster recovery and fewer post-operative infections when compared with open techniques(13, 15, 
26-32). A recent systematic literature review of 460 publications(33) was performed to examine the potential 

 
 
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complication of MIS and traditional surgery. A similar incidence of dural tears, infection, screw malpositioning, 
root injury and revision surgery rates was reported in both MIS and open surgery patients.  
A systematic review of 258 publications regarding lateral fusion techniques (LLIF, XLIF(R), or DLIF)(34) examining 
the comparative safety and effectiveness for lateral techniques concluded that there was not sufficient evidence 
to compare the effectiveness of LLIF versus PLIF/TLIF surgery(34). However, the patients in the LLIF group 
experienced less estimated blood loss and a lower mortality risk compared with the PLIF group. No permanent 
neurological impairment, vascular or visceral injuries were observed in 97 consecutive patients from three 
different centers at a mean FU of 12 months(35). A rare complication of bowel perforation for XLIF in a 70-year 
old male was reported(36). ALIF open lumbar interbody fusion technique was associated with retrograde 
ejaculation (RE), demonstrating an increased risk (6.3%) in patients which received BMP-2 than in patients that 
were not exposed to BMP-2 (0.9%)(37). In fact, when using the rhBMP-2 in spinal fusion surgery a 10-50 times 
higher risk for AE than compared with sponsored peer-review publications(38) was communicated.  
Concerns have been expressed about the instrumented fusion leading to a more stiff spine, and thus, to an 
increased risk for adjacent segment disease (ASD). ASD requires often re-operation, and is reported to be a 
common problem after lumbar spine fusion. However, there was no statistically significant difference of ASD 
incidence in patients undergoing open or percutaneous ALIF(8). Preoperative degenerative changes and post-
operative sagittal imbalance were however important factors for developing ASD(39), along with high BMI(40) 
with a majority of the ASD re-operations being performed > 5 years post-surgery(41). A meta-analysis 
demonstrated that, when comparing with motion-preserving procedures, fusion patients were at higher risk of 
developing ASD(42). Within 10 years after surgery, it was predicted that 10% of patients would undergo additional 
surgery for ASD after index lumbar fusion, with PLIF (43, 44) and age > 60 years being risk factors.  
 
Clinical outcomes after open spine fusion procedures in patients with degenerative conditions were reported to 
deteriorate continuously after 6 months post-surgery in a large cohort study with 6,376 patients, with 
approximately 18% having procedure-related complications, and 20% of these patients having a re-operation 
within 5 years. The complications occurred more frequent in patients having fusion than in patients having 
laminectomy or discectomy alone(45). Higher levels of back pain in 1,310 patients with DDD which had undergone 
an instrumented PLIF, at two years after surgery(46). However, the QoL was similar between the groups at 2 years 
post-surgery. MIS TLIF was comparable with open TLIF in terms of midterm clinical outcomes and fusion rates with 
the additional benefits of less initial postoperative pain, less blood loss, earlier rehabilitation, and shorter 
hospitalization, and a lower complication rate (47). There was no significant difference of ASD incidence in patients 
undergoing open versus percutaneous instrumented fusion following ALIF(8) or TLIF(48) procedures. It was 
suggested that MIS TLIF could be associated with decreased long-term morbidity compared with open fusion 
approaches(48), and had better results. In patients with degenerative spondylolisthesis MIS TLIF was equally 
effective as the conventional open TLIF procedure(47, 49-52), even though the quality of the available literature 
was questioned(53). MIS TLIF was a more cost-effective treatment than open TLIF for patients with degenerative 
spondylolisthesis and was equally effective as the conventional open TLIF procedure, although further financial 
analysis, including an analysis of indirect costs, is needed to better understand the full benefit of MIS TLIF (14, 53, 
54).  
 
A.2 
Device information 
The main set of devices that should be used in this study is the Medtronic CD Horizon® Spinal System. CD 
HORIZON® Spinal System consists of a variety of rods, hooks, screws, plates, and other connecting components 
used to build a spinal construct. Instrumentation is also available to facilitate implantation of these components. 
Additionally, other Medtronic family of ancillary devices, implants, instrumentation and bone grafts and 
substitutes (which are referred to as ‘Devices’) will also be used in the minimal invasive procedures within the 
scope of this study.  

 
 
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All Medtronic Devices to be used in this study, as listed below, shall be used within their intended use as described 
in the approved manual and Instructions for Use for which Medtronic obtained regulatory market release (e.g. CE 
Marking in Europe). Labeling of the devices will be in the appropriate local language. It is an investigator’s 
responsibility to only use commercially available devices within intended use in the scope of this study.  
In addition, any future approved similar devices or models may be used in the study. 
 
 Posterior Fixation (Stabilization) Systems  
The CD HORIZON® Spinal System consists of a variety of shapes and sizes of rods, hooks and screws that has the 
function to help provide immobilization and stabilization of spinal segments as adjunct to fusion. The MAST™ 
platform provides generic instruments used to implant some of the CD Horizon® families of implants. The following 
systems are used for posterior stabilization of the treated spinal segments:  
• 
CD HORIZON® FENESTRATED Spinal System 
• 
CD HORIZON® LONGITUDE™ Multi-Level Percutaneous Fixation System 
• 
CD HORIZON® LONGITUDE™ II Multi-Level Percutaneous Fixation System 4.75  
• 
CD HORIZON® LONGITUDE™ II Multi-Level Percutaneous Fixation System 5.5/6.0  
• 
CD HORIZON® LEGACY™ 5.5 Spinal System (Solid and cannulated screws) 
• 
CD HORIZON® SEXTANT® Rod Insertion System 
• 
CD HORIZON® SEXTANT® II Rod Insertion System 
• 
CD HORIZON® SEXTANT® II Spondylolisthesis Reduction System 
• 
CD HORIZON® SOLERA® 4.75 Spinal System (Solid and cannulated screws) 
• 
CD HORIZON® SOLERA® 5.5/6.0 Spinal System (Solid and cannulated screws) 
• 
CD HORIZON® SOLERA® VOYAGER™  
 
 Access Systems  
The MAST™ (Minimal Access Spinal Technologies) platform incorporates instruments that allow the surgeon, in a 
minimally invasive approach, to reach the targeted lumbar anatomy by splitting the muscles with the insertion of 
a sequence of dilator tubes and reach the preferred tubular retractor diameter. This minimally invasive access 
allows a clear intraoperative visualization to perform the surgical procedure. The families of retractor systems, but 
not limited to, that may be used are: 
• ENDO-RING™ surgical retraction system  
• MAST QUADRANT® Retractor System 
• MAST QUADRANT™ Lateral Retractor System 
• MAST™ MIDLF™ Retractor System 
• METRx® II System 
• METRx® X-tube® Retraction System  
• 51 Access System 
• Other commercially available minimally invasive access systems  
 

 
 
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 Cages Systems 
These are devices placed in the intervertebral space between two vertebrae to replace a disc and/or to restore 
disc height. These families of devices including the necessary instrumentation for their placement that may be 
used, but not limited to, are: 
• 
CAPSTONE® PEEK Spinal System  
• 
CAPSTONE®TI Vertebral Body Spacer 
• 
CAPSTONE PTC™ Spinal System 
• 
CAPSTONE CONTROL™ Spinal System 
• 
CRESCENT™ System 
• 
CRESCENT® Spinal System Titanium 
• 
CLYDESDALE™ Spinal System 
• 
FUSE™ Spinal System 
• 
I-FLY™ Threaded Fusion Device 
• 
INTER FIX™ Threaded Fusion Device 
• 
LOOP® Spinal System 
• 
LT-CAGE® Lumbar Tapered Fusion Device 
• 
SOVEREIGN™ Spinal System 
• 
TELAMON® Vertebral Body Spacer 
• 
VERTE-STACK® PERIMETER® PEEK Vertebral Body Spacer 
• 
WAVE-D Spinal System® 
• 
WAVE O Spinal System® 
• 
AVILA™ Interbody Fusion Device 
• 
Other commercially available cage systems 
 Plates 
Plates are devices used to obtain anterior stable, rigid segmental fixation. The family of devices including the 
necessary instrumentation for their placement that may be used, but not limited to, is: 
• 
PYRAMID™ Anterior Lumbar Plate  
• 
Vantage™ Anterior Fixation System 
• 
CD HORIZON® LEGACY™ Anterior Spinal System  
• 
Other commercially available anterior plates 
 Bone Grafts and Substitutes  
Bone grafts and substitutes are used to promote bone formation which is necessary for a strong and successful 
fusion. The following, but not limited to, osteoconductive bone graft substitutes may be used:  
• 
BCP BiCalPhos® granules 
• 
GRAFTON® Demineralized Bone Matrix 
• 
InductOs®/ Infuse® 
• 
MAGNIFUSE BONE GRAFTS 
• 
MASTERGRAFT™  
• 
Nanostim™ Synthetic Bone Paste 
• 
Other commercially available bone grafts and substitutes  

 
 
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B 
STUDY PLAN 
B.1 Study Objectives and Clinical Endpoints  
 Study Objectives 
The MASTERS-D 2 clinical study aims: 
• 
To evaluate the effectiveness of MAST techniques for anterior/lateral and posterior approaches in 
patients with spondylolisthesis (≥ grade I).  
• 
To assess how single or double level MAST fusion procedures PLIF, TLIF, DLIF, OLIF, ALIF, or MIDLF are 
used in surgical practice and to describe long-term safety and effectiveness in a broad patient 
population of patients with degenerative lumbar disc disease .  
 Primary objective and endpoint 
 
Primary objective: To demonstrate that DDD patients operated for spondylolisthesis fare equally well regardless 
of the surgical procedure (anterolateral or posterior) performed as measured by the improvement of Oswestry 
Disability Index (ODI) at 3 months as compared to baseline. 
 
Primary endpoint: Improvement of disability at 3 months post-operatively as compared to baseline. 
 
In this prospective study design, patients will be enrolled in one of the 6 procedure groups: ALIF, OLIF, DLIF, PLIF, 
TLIF or MIDLF. Patients treated with an ALIF, OLIF or DLIF procedure will be assigned to the anterolateral 
procedure group and patients treated with a PLIF, TLIF or MIDLF procedure will be assigned to the posterior 
procedure group. 
 
• 
Rationale for primary endpoint selection 
The accuracy of an outcome instrument is dependent on its reliability, validity and responsiveness (5). The 
rationale for selecting the Oswestry Disability Index (ODI) is that it is reliable, accurate and has a good 
responsiveness, in addition it is translated to several languages and validated.  
The Oswestry Disability Index (ODI) was used to assess pain and disability in the original MASTERS-D trial 
(NCT01143324), and is one of the principal instruments for managing outcomes in spine disorders, including 
lumbar fusion techniques in patients with chronic low-back pain disorders. The ODI is registered with the 
International Consortium for Health Outcome Measures as a standard outcome measure (55, 56). It is spine-
specific, considered as the “gold standard” by several systematic reviews (4, 56, 57) and recent surgery 
guidelines(5), validated for different languages, used in numerous randomized controlled trials and long-term 
follow up studies(3, 58), for different follow-up periods (57, 59, 60). It has been shown that the smallest change 
score to represent a real change beyond measurement error with 95% probability in one individual (MDC95) is 
11.75, with SEM (standard error of mean) of 4.24(4). The ODI score was able to detect clinically relevant changes 
(61) after surgical treatment for low-back pain. Clinical relevant changes were evident also when the ODI was used 
to compare MIS techniques with each other or with open surgery techniques (3, 62). The highly cited SPORT-study 
used the ODI for its consistency with interpretation of the SF-6D (63-65) in comparing surgical with non-operative 
treatment in patients with intervertebral disc herniation, spinal stenosis, and degenerative spondylolisthesis. 
Furthermore, ODI was also used to generate utility values(6) in lumbar fusion patients.    
SWESPINE, the Swedish national Spine register, is reporting outcomes related to lumbar spine disorders treated 
in patients diagnosed with disc herniation, spinal stenosis, spondylolisthesis and degenerative disc disease and 

 
 
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treated with lumbar surgery over the last 20 years. Significant functional disability improvements from baseline 
measured by the ODI score were reported at 1-, 2-, and 5-year follow-up data. The results seemed to be stable 
over time(66). Results from the MASTERS-D study showed that significant improved outcomes could occur much 
earlier (9), in patients with degenerative lumbar disorders treated with minimally invasive lumbar interbody fusion 
(MILIF).  The present study aims to further investigate the effects of MILIF surgical techniques, while also having a 
pathology based approach.  
This study intends to investigate functional improvements that occur at 3 months post-surgery, in patients with 
spondylolisthesis, treated by a minimally invasive surgery technique, thus adding to the existent body of evidence. 
Secondary outcomes, for patients diagnosed spondylolisthesis at longer follow up, and for patients diagnosed with 
stenosis, with/without spondylolisthesis, are also aimed to be reported at different follow up intervals(16). 
 Secondary objectives and endpoints 
 
1. To evaluate whether DDD patients without spondylolisthesis fare equally well regardless of the surgical procedure 
(anterolateral or posterior) performed, as measured by Oswestry Disability Index (ODI) at 3 months 
 
2. To observe and document clinical and radiological  outcomes through 5 year follow-up (except for ODI at 3 
months) 
• 
Endpoints: 
a) Improvement of ODI as compared to baseline 
b) Improvement of VAS back- and leg pain intensity as compared to baseline 
c) Improvement of EQ-5D as compared to baseline 
d) Neurological success 
e) Fusion success  
f) 
Secondary Surgeries at index and/or adjacent level(s)  
g) Adverse Events 
 
3. To observe and document the patients’ short term recovery after surgery 
• 
Endpoints: 
a) Time needed for first ambulation: Days needed for patient to get out of bed and ambulate with or 
without assistance 
b) Surgery Recovery Day: Days after the surgery, fulfilling following criteria: 
i. 
No need for intravenous infusion of analgesic drugs 
ii. 
No ongoing surgery related adverse events impeding discharge  
iii. 
No need for nursing care 
 
4. To document health resources consumption and perform economic analyses. 
 
5. To observe and document the patient profile when choosing a particular minimally invasive fusion procedure.  
 
The primary endpoint and the secondary endpoints outlined in secondary objectives 2 and 3 of will be analyzed 
for all DDD patients and the following subgroups: 
1) In DDD patients with spondylolisthesis and stenosis 
2) In DDD patients with spondylolisthesis but without stenosis 
3) In DDD patients with stenosis but without spondylolisthesis  
4) All patients not included in subgroup 1), 2), 3).  

 
 
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The grade of spondylolisthesis will be evaluated according to the Meyerding grading system (Grade I < 25%, Grade 
II is 25-49%, Grade III is 50-74% and Grade IV is 75-99% sagittal slip, Grade V if the vertebral body completed slips 
from the body below (spondyloptosis)). 
 
• 
Rationale for selection of the secondary endpoints  
 
VAS back / leg pain 
The study requires an assessment of the level of pain and pain like symptoms in the back and the legs. Although 
quantification of pain remains a great challenge, patient completed visual analogue scales (VAS) are the preferred 
method to quantify pain or the changes thereof. Thus VAS is used in our study as well to quantify pain and pain 
like symptoms in the back and legs. 
The study utilizes VAS in order to assess the magnitude and the eventual changes in these two pain types.  
A standardized visual analogue scale (VAS, 0-10) will be used to evaluate the level of intensity of leg and back pain 
as perceived by the patient, where 0 is no pain and 10 is the worst pain possible. 
 
EQ-5D questionnaire 
Health-related quality of life will be assessed by using the five-item EQ-5D questionnaire at the study center, with 
three levels for each dimension: no problems, some problems, or extreme problems. EQ-5D index scores will be 
obtained using the UK population value set (http://www.euroqol.org). The EQ VAS will also be utilized to 
document the patient’s self-rated overall health state on a 0 to 100 scale (0 = maximal health-related problems, 
100 = minimal health-related problems).  
Generic tools such as Euroqol (EQ-5D) are currently used in spine surgery practice due to several advantages(67). 
The score has been validated in different populations, diseases, setting and for different languages, allowing 
comparisons(68). Moreover, it allows the evaluation of cost-effectiveness(68). EQ-5D is increasingly used in spinal 
research(69-71), and it has outcomes in spinal surgery(4, 69, 70).  
 
Neurological status 
Neurological status will be evaluated both prior to the surgery and throughout the study. 
Neurological status is based on four types of measurements (sections): motor, sensory, reflexes, and straight leg 
raising. Each of the sections is comprised of a number of elements. Following scales will be used to evaluate 
neurological status: reflexes (0 = Absent or Trace, 1 = Hyper-reflexic, 2 = Normal), sensory function (Light Touch 
or Pin Prick L1 to S1), motor function (using 0-5 scores 0-5 whereas 0= Total Paralysis, 1 = Palpable or Visible 
Contraction, 2 = Active Movement, Gravity Eliminated, 3 = Active Movement, Against Gravity, 4 = Active 
Movement, Against Some Resistance and 5 = Active Movement, Against Full Resistance (full strength) and 
straight leg raise (positive = patient experiences radiating leg pain below the knee on elevating the leg between 
15 and 70 with the knee extended, normal = no pain is experienced on elevating the leg between 15 and 70 with 
the knee extended). 
Overall neurological success will be defined as maintenance or improvement in all sections (motor, sensory, 
reflex, and straight leg raising) for the time period evaluated. In order for a section to be considered a success, 
each element in the section must remain the same or improve from the time of the baseline evaluation to the 
time period evaluated. Therefore, if any one element in any section does not stay the same or improve, then a 
patient will not be considered a success for neurological status. 
 
Fusion  
From the surgical point of view, fusion is the main target of performing the procedure.  
Fusion will be assessed at 1 year, preferably by collecting a CT-scan, alternatively fusion may also be collected 
thru X-Rays. If no fusion is observed during the first fusion assessment further fusion assessment(s) will be at the 
discretion of the investigator. The criterion for fusion when assessed thru a CT-scan is bony bridging and when 
assessed thru X-Rays the criteria are bony bridging, no motion (<4˚) in Flexion/Extension views and integrity of 

 
 
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instrumentation (implanted devices). The surgeon or hospital radiologist will determine fusion. Fusion success 
rate will be summarized at 1, 2, 3, 4, 5 -year follow-up. If a subject shows fusion success at early timepoints and 
non-fusion at a later timepoint, the fusion status at all earlier points should be considered as non-fusion. For 2-
level subjects, fusion success will be defined as achieving fusion at both treated levels.  
 
Proportion of patients needing a second surgery at the index and/or adjacent level(s) (reoperation rates) throughout 
the study  
When a patient requires additional surgery at the index and/or adjacent level(s), it can be an indicator of 
insufficient outcomes of the initial surgery. As such, this is a reflection of the efficiency of the initial surgery and 
therefore is of great clinical value to the surgical community and through that to the patients. Due to the 
progressive nature of the degenerative lumbar spine, additional surgeries at the index and/or adjacent level might 
be required after the initial surgery. To ensure all safety and economic values are collected, the revision surgeries 
and their complication types and rates will be assessed during the study as assessed by the surgeons.  
In case the investigator or hospital becomes aware of a second surgery at the index and/or adjacent level in 
another hospital, this should also be documented in the  AE  eCRF.  
 
Document Adverse Events occurrence throughout the study 
The study is designed to observe and document events related to clinical safety and performance of the devices 
according to approved instructions for use. During the follow up period (up to 5 years), the occurrence of all AEs 
will be monitored, registered and analyzed. To safeguard the safety of the clinical study subjects, all AEs will be 
collected even those that may not be directly related to the surgery. 
  
Time in days needed for first ambulation  
The time in days needed for first ambulation with or without assistance will be part of clinical outcome measures 
to document the patient’s short term recovery of the surgery. Ambulation will be defined in this study as ability 
to walk with or without assistance.  
 
Surgery Recovery Day  
The objective of the Surgery Recovery Day assessment is to collect the day when the patient could be discharged 
based on his actual clinical condition because the effective day of discharge may be prolonged by factors other 
than the patient's clinical recovery such as social factors or co-morbidity. 
For the purpose of reporting these parameters the day of the surgery will be considered ‘D0’, the first day after 
surgery as ‘D1’, the second day as ‘D2’ and so on. 
 
 Additional Measurements 
Other measurements in the study will be co-morbidities, hospital discharge day, rehabilitation program, pain 
medication consumption throughout the study, days to first return to work, additional medical visits related to 
back pain, sagittal balance. 
 
Co-morbidities 
Comorbidities can be either medical condition(s) existing simultaneously but independently with another 
condition; or it can indicate a related medical condition or conditions. Comorbidities may affect the outcomes of 
the surgery. 
 
Hospital Discharge Day  
Days after the surgery when patient has been discharged from hospital.  
 

 
 
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Rehabilitation program 
Information on the rehabilitation venue and program will also be collected in order to assess how many patients 
will have rehabilitation in an in-patient setting, at home or in an outpatient rehabilitation unit. Corresponding 
costs will be evaluated and included in the economic analyses. 
 
Pain Medication consumption throughout the study 
When assessing the economical outcomes after surgical treatments in chronic diseases such as Degenerative 
lumbar spine, it is essential that pain medication consumption of the patients is also collected.  
 
Days to first return to work  
Information on the days needed to first return to work will also be collected by the patient for the investigator in order 
to assess how long it takes for patients to return to work. Corresponding costs will be evaluated and included in the 
economic analyses.  
 
Additional Medical visits  
Information on additional medical visits related to the spine that are not related to the study protocol will be 
collected throughout the study (e.g. outpatient consultations, visits to primary care services, visits to general 
practitioner).  
 
Sagittal Balance 
Collection of Sagittal Balance parameters can show us if the patient’s spine is balanced or not prior to or after 
the surgery. Any evolution of parameters after the surgery can indicate a change in Sagittal Balance or a 
mechanism of regulation / compensation due to an evolution of the spinal alignment. Sagittal balance 
parameters may include Pelvic Incidence, Sacral Slope, Pelvic Tilt, Global Lordosis Angle, Lordosis Apex Location 
and Inflection Point Limit.  
Sagittal balance data will be assessed by the investigator and only be collected by the sites if it is part of standard 
of care at the hospital.  
 
DN4 questionnaire, (Douleur Neuropathique 4 (neuropathic pain)) 
The French Neuropathic Pain Group developed a validated clinician-administered questionnaire named DN4 
consisting of both sensory descriptors and signs related to bedside sensory examination(72). Identification of 
neuropathic components is important for characterization of chronic pain patients. The 10 questions are 
answered by subject interview and clinical examination. The first seven items are related to the quality of pain 
(burning, painful cold, electric shocks) and its association to abnormal sensations (tingling, pins and needles, 
numbness, itching). The other 3 items are related to neurological examination in the painful area (touch 
hypoesthesia, pinprick hypoesthesia, tactile allodynia). A score of 1 is given to each positive item and a score of 0 
to each negative item. The total score is calculated as the sum of all 10 items. A score of at least 4/10 in this 
questionnaire is indicative of neuropathic pain, with excellent sensitivity and specificity (73). Two questionnaires 
will have to be completed, one will be completed to address the neuropathic pain specifically in the leg and one 
specifically in the back. 
 
Additional spinal cord stimulation or pain pump 
When a patient requires spinal cord stimulation or pain pump, this should also be documented in the AE CRF. 
B.2 Study Population 
Patients enrolled in this study will receive a single or double level instrumented fusion using minimally invasive 
PLIF, TLIF, MIDLF, DLIF, OLIF or ALIF procedures. Please see a list of abbreviations at section K.4 of this protocol.  

 
 
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B.3 Definitions Study Procedures  
In order to make a clear distinction between the different techniques the following definitions will apply: 
For the posterior procedures: 
• 
TLIF: Fusion Procedures targeting the disc space with a trajectory lateral to the medial pedicle wall.  
• 
PLIF: Fusion procedures targeting the disc space with a trajectory medial to the medial pedicle wall (in 
the coronal plane).  
• 
MIDLF: Fusion procedures with a medial to lateral pedicle screw trajectory deep to the segmental back 
muscles and with the screw construct placed into the pedicle through cortical bone. 
Fixation, decompression, and interbody fusion through a laminectomy approach. 
For the anterolateral procedures: 
• 
DLIF: Fusion Procedures with a Lateral Transpsoas approach via a smaller incision and dilatation. This 
technique would also be named Lateral Lumbar Interbody Fusion in literature.  
• 
OLIF:  
o 
OLIF25: Access to L2-L5, approach via oblique corridor between the aorta and the psoas avoiding 
the lumbar plexus and iliac crest. 
o 
OLIF51: Access to L5-S1, approach via oblique corridor between the iliac vessels 
• 
ALIF: Anterior incision, transperitoneal or retroperitoneal approach. Disc access L4-L5 or L5-S1.  
  
B.4 Study hypothesis 
The study hypothesis for the primary objective is to verify whether DDD patients operated for spondylolisthesis 
(≥ grade I) have equivalent mean improvement of ODI at 3 months regardless of the minimally invasive surgical 
procedure (anterolateral or posterior) used.  
 
More specifically: 
The null-hypothesis;  
Ho: Δ ODI_Anterolateral ≠ Δ ODI_posterior 
 
will be tested against the alternative hypothesis  
HA: Δ ODI_Anterolateral = Δ ODI_posterior 
 
Where Δ ODI_Anterolateral is the average improvement in ODI score (baseline - 3 months) in spondylolisthesis DDD 
subjects treated with the anterolateral approach and Δ ODI_posterior is the average improvement in ODI score 
(baseline - 3 months) in spondylolisthesis subjects treated with the posterior approach. 
 
The study hypothesis for the first secondary objective is to verify whether DDD patients operated for non-
spondylolisthesis have equivalent mean improvement in ODI at 3 months regardless of the minimally invasive 
surgical procedure (anterolateral or posterior) used. More specifically: 
 
The null-hypothesis;  
Ho: Δ ODI_Anterolateral ≠ Δ ODI_posterior 
 
will be tested against the alternative hypothesis  

 
 
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HA: Δ ODI_Anterolateral = Δ ODI_posterior 
 
Where Δ ODI_Anterolateral is the average improvement in ODI score (baseline - 3 months) in non-spondylolisthesis 
subjects treated with the anterolateral approach and Δ ODI_posterior is the average improvement in ODI score 
(baseline - 3 months) in non-spondylolisthesis subjects treated with the posterior approach. 
 
There is no hypothesis testing for other secondary objectives with descriptive nature for the analyses. 
 
B.5 Study design 
The MASTERS-D 2 study is a Prospective, Global clinical trial. Commercially available study devices will be used 
within their intended use.  
 
The indication for the treatment of a patient will be at the discretion of the surgeon.  
As such the assignment of a patient to a particular surgical intervention is not required within this clinical study 
protocol but falls within standard of care practice.  
 
All fusion procedure patients will be screened consecutively against the eligibility criteria. Every effort will be made 
to enroll subjects in a consecutive manner.  
Study enrollment is open to eligible subjects who in the opinion of the investigator are candidates for a minimally 
invasive lumbar fusion surgery.  
The investigator or authorized designee must obtain written informed consent/ data release consent from the 
patient before any clinical study related activity takes place. The patient has the right to refuse and refusal will not 
affect the care of the patient. The patient can opt out at any time from the study. Refusal of study participation as 
well as enrollment into the study will be recorded on the screening log. 
 
The following measures have been taken to avoid bias: 
o 
Consecutive screening and enrollment is encouraged and enforced as much as possible.  
 
When all inclusion/exclusion criteria are fulfilled for a patient, then the patient should be 
enrolled in this study. A screening log will be maintained at each site documenting the patients 
that have been screened and identified to be eligible or ineligible for the study, declined 
patients and enrolled patients.  
 
In case the group with one of the approach procedures has reached the maximum amount of 
patients per procedure in a specific region, further enrollment of subjects into the procedure 
will be terminated. An email will be sent to the participating sites to inform the investigators 
when the enrollment for a specific procedure is complete. 
o 
A multi-center design is used to help ensure a representative sample of surgeons performing the 
procedure and to ensure a reasonable enrollment period 
o 
Only surgeons that have adequate experience (> 30 minimally invasive lumbar fusion procedures) can 
participate 
o 
Site training will be performed to assure full understanding and engagement to comply with the study 
design and all protocol requirements  
o 
Preferably, the ODI outcome measurements at 1, 3 months and 1, 2, 3, 4, 5 year follow up will be done 
by site staff different than the surgeon who operated the patient. The site staff will be trained to collect 
the ODI outcome measurements in an independent way without influencing the patients.  
 

 
 
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B.6 Randomization and blinding 
Randomization and blinding is not applicable in this study.  
 
B.7 Sample size 
The primary objective is to evaluate if DDD patients operated for spondylolisthesis fare equally well regardless of 
the surgical procedure (anterolateral or posterior) performed, measured by the improvement of Oswestry 
Disability Index (ODI) 3 months after the surgery. 
 
For the initial sample size calculation “equally well” was defined as a difference in ODI improvement at 3 months 
between groups  within the range of (-7.5, 7.5) points. However, taking into account  literature (74, 75) and the 
opinion of the Study Advisory board the equivalence range was increased to (-10, 10) points. As patient enrollment 
is slower than initially forecasted, the increase in equivalence range also allows completing enrollment timely  
If the difference in ODI improvement at 3 months between the anterolateral procedures group and the posterior 
procedures group is within the range of (-10, 10) points, the anterolateral and posterior treatment options will 
be considered equivalent in terms of effectiveness. 
Assuming that the standard deviation for ODI improvement at 3 months is 20 for both groups (anterolateral and 
posterior) and there is no difference in the mean ODI improvement at 3 months, with 80% power and 5% alpha 
level, the sample size per group is 70 in order to claim equivalence of the primary endpoint between two groups 
with equivalent margin (-10, 10) 
 
Estimated sample size per group  
(anterolateral procedures versus posterior procedures): 
70 
Estimated total sample size for spondylolisthesis patients with DDD: 
140 
 
From the MASTERS-D study it is known that approximately 50% of the patients with degenerative disc disease 
have spondylolisthesis ≥ grade I. Hence the required total sample size is 140/0.5 = 280.  
The study is anticipated to enroll 350 patients. The amount of patients with spondylolisthesis versus non-
spondylolisthesis will be monitored during the study. In case the study team identifies that the target amount of  
spondylolisthesis patients for the anterolateral procedures and posterior procedures might not be reached, the 
sites might receive instruction to limit the enrollment of non-spondylolisthesis patients. This action will secure 
the enrollment of target sample size as calculated for the primary endpoint. Additionally, it might be decided to 
stop patient enrollment completely when the required sample size for the primary endpoint has been reached. 
It is expected that approximately 350patients will be enrolled in this study from approximately 30 sites in Europe, 
Middle East, Latin America and Asia Pacific. This study will be open for enrollment to other countries in order to 
meet the required patient numbers. Sites have been selected based upon an anticipated enrollment for each 
minimally invasive fusion procedure. Consecutive enrollment will apply per minimally invasive procedure (i.e. ALIF, 
OLIF, DLIF, PLIF, TLIF and or MIDLF). 
To allow the different regions to contribute patients to this study, a maximum enrollment per country/region 
might be defined during the course of the study This will be timely communicated to the investigators and they 
will be requested to stop enrollment when the country/regional anticipated maximum number of patients has 
been reached. Patient enrollment limits per site for each country/region are indicated in Table 1. These limits may 
be subject to change during the course of the study and will be communicated as appropriate to the investigators 
and EC/IRB, if required.  
The distribution of the procedures differs among the regions. Patient distribution accross different surgical 
procedures will be in accordance with natural distribution in the country, but the study will aim to balance the 

 
 
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subjects between the procedures. Nevertheless, a minimum enrollment of 20 patients in each procedure (ALIF, 
OLIF, DLIF, PLIF, TLIF or MIDLF) is required for the study. A broad usage of both anterolateral and posterior lumbar 
fusion procedures is encouraged at all sites even though it is acknowledged that a user preference will apply. 
Enrollment limits per procedure have been defined for sites in China as these sites are allowed to enroll more 
patients than sites in other regions (Table 1). Investigators will be requested to stop enrollment when the 
maximum enrollment for that procedure at their site has been reached.  
 
 
Table 2: Overview of patient enrollment limits in Europe, Latin America, Middle East and Asia Pacific per site and per 
procedure. 
REGION 
EUROPE 
LATIN AMERICA 
CHINA 
KOREA 
Enrollment max per site 
40 
20 
120 
20 
Enrollment maximum per 
procedure for each site* 
40 
 
20 
75 
20 
Estimated Number of sites 
21 
3 
3 
3 
* Enrollment limits per procedure might change to obtain a better distribution of procedures amongst the sites 
and regions and reach the minimum enrollment of 40 patients in each procedure. Any change in enrolment 
limitations will be communicated to the sites. 
B.8 Number of investigation sites and study duration 
Approximately 350patients will be enrolled over a period of around 4 years in approximately  30 sites located in 
Europe, Latin America and Asia Pacific. This study is open to other countries/regions as long as the Devices are 
approved for market release in those countries with the same indications as in the European Community. As the 
patients will be followed during a period of 5 years after the surgical procedure, the total duration of the study 
will be of approximately 9 years. Depending on enrolment progress, study timelines are subject to change. 
A list of participating investigation sites and investigators will be kept separate from this CIP at the sponsor’s 
Project Files and the Investigator Site Files. The sponsor will keep this list up to date. 
C 
SUBJECT SELECTION 
C.1 
Inclusion and exclusion criteria 
The Inclusion Criteria for this study are: 
• 
Patient is ≥ 18 years of age (or minimum age as required by local regulations) 
• 
Patient has degenerative disc disease and an indication for a single or double level instrumented lumbar 
fusion for the treatment 
• 
Patient agrees to participate in the study and is able to sign the Data Release Form/Informed Consent 
• 
The procedure planned for the patient complies with the labeling of the Devices that may be used in 
the surgical procedure as described in the section Device information above 
• 
Patient is planned to be submitted to a minimally invasive fusion procedure using a posterior (PLIF, 
TLIF, MIDLF) or anterolateral (OLIF, ALIF, DLIF) technique*.  
• 
The patient is willing and is able to perform study procedures and required follow-up visits.  
* For a double level instrumented fusion, the same procedure must be used for both levels. 
The Exclusion Criteria for this study are: 

 
 
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• 
Patient that has already undergone a lumbar fusion surgery 
• 
Patient that has already undergone open lumbar surgery other than standard decompression surgery 
• 
Indications for the procedure other than degenerative spine disease like: Osteoporotic vertebral 
fractures, Spine trauma fractures or Spine tumor 
• 
Illiterate or vulnerable patients (e.g. minors, participants incapable of judgment or participants under 
tutelage)  
• 
Concurrent participation in another clinical study that may confound study results. 
 
D STUDY PREPARATION PROCEDURES 
D.1 Investigator/Investigation site selection 
The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical study as 
well as ensure data integrity and the rights, safety and well-being of the subjects involved in the clinical study. 
Sites will be nominated and selected for this study based upon screening against a list of selection criteria. 
Compliance with the components of the list is intended to ensure high quantity and quality data. An investigation 
site may be included in this study if the investigation site complies with the following requirements: 
• 
The operating study surgeons must have a minimum previous experience of at least 30 instrumented 
minimally invasive lumbar interbody fusion procedures for degenerative lumbar spine indications. 
• 
The operating study surgeons must have recognized expertise in at least one of the surgical techniques 
which are the objective of this study PLIF, TLIF, ALIF, OLIF, DLIF and/or MIDLF 
• 
Site must have sufficient patient population  
o 
Annual Case volume of > 30 minimally invasive lumbar fusion procedures 
o 
Ability to enroll at least 10 patients over a period of 12 to 18 months. 
• 
Investigator must have interest in clinical research and motivation to participate in the study. 
• 
Site will assess fusion at 1 year FU by CT scan or X-Rays as standard of care. 
• 
Investigator should have adequate staff that has time to perform data collection and electronic data 
capture. 
• 
Investigator and his study staff must be willing to comply with applicable regulations and this Clinical 
Investigation Plan (Protocol).  
• 
Have internet connection at the site with sufficient data transfer speed to facilitate data entry in the web 
based eCRFs. 
• 
Willing to undergo monitoring and auditing by sponsor or relevant regulatory authorities 
• 
Willing to undergo required study training 
• 
Willing to enroll subjects in a consecutive manner 
 
In addition, the site and Investigators will also be selected based on geographic location and/or previous 
participation in the MASTERS-D study.  
 Clinical Investigation Agreement 
A Clinical Investigation Agreement shall be in place, signed by the participating investigation site and/or principal 
investigator of each investigation site, as per the local legal requirements, and returned to Medtronic prior to the 
commencement of any clinical study activities. The investigator is indicating approval of the Clinical Investigation 
Plan and subsequent amendments, by a fully executed agreement. Amendments to this Clinical Investigation Plan 

 
 
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shall be agreed upon between Medtronic and investigator(s) and be recorded with a justification for the 
amendments. 
 Curriculum Vitae 
Prior to study start, an up to date signed and dated curriculum vitae shall be collected from each investigator 
participating in this clinical study, evidencing the required qualifications, including the year and where obtained, 
and shall include their current position at the investigation site. The signature on the CV must be dated within 3 
years prior to the date of activation of the site.  
D.2 Ethics 
All patients enrolled in this study must be able to give the Data Release or Patient Informed Consent whichever is 
applied.  
 EC/IRB approval 
 
EC/IRB approval depends on local law/hospital requirements. If not required by the hospital, written 
documentation from the investigator is required. However, when the sponsor is responsible for EC submission, a 
written documentation from the sponsor is required.  
EC/IRB requirements may vary from site to site and from country to country. This is especially applicable for studies 
under the scope of a post market release design.  
Some EC/IRB will require a full submission of the study documentation including a Patient Informed Consent Form 
or Data Release Form and will inform the investigator in writing that there are no objections to start the study 
after a review according to their procedures. Other EC/IRB might only require to be notified about the planned 
conduct of this study, while some sites do not require EC/IRB involvement to start the study. 
It is the responsibility of the investigator to confirm the approval requirements of the hospital and local regulations 
for this study with his/her EC/IRB prior to start this study.  
 
In case EC/IRB approval is required per local law/ hospital regulations: 
Prior to enrolling subjects in this clinical study, the investigation site’s EC/IRB will be required to approve the 
current Clinical Investigation Plan, the Patient Information and Informed Consent form. EC/IRB approval of the 
clinical study must be received in the form of a letter and provided to Medtronic before commencement of the 
clinical study at an investigation 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. In addition, the approval letter needs to be accompanied 
by an EC/IRB roster or letter of compliance, to allow verification that the investigator, other investigation site 
personnel, and/or Medtronic personnel are not members of the EC/IRB. If they are members of the EC/IRB, written 
documentation is required stating that he/she did not participate in the approval process. If the EC/IRB imposes 
any additional requirements (e.g. safety reports, progress reports etc.), Medtronic will prepare the required 
documents and send them to the investigator for reporting to the EC/IRB. Investigators must inform Medtronic of 
any change in status of EC/IRB approval once the investigation site has started enrollment. If any action is taken 
by an EC/IRB with respect to the investigation, that information will be forwarded to Medtronic by the respective 
investigator. 
 
In case EC/IRB notification is required per local law/ hospital regulations: 
For investigation sites in which the local EC/IRB only needs to be notified about this study, the investigator needs 
to provide a copy of the EC/IRB notification letter to Medtronic prior to enrolling subjects in the clinical study. For 
the initial submission and any subsequent CIP amendment, the investigator needs to sign a statement (available 

 
 
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at Appendix K.6) confirming that this approach is in accordance with local regulations. However, when the sponsor 
is responsible for EC submission/notification, written documentation from the sponsor is required. 
 
In case neither EC/IRB notification nor approval is required per local law/ hospital regulations 
If neither approval nor notification from the EC/IRB is necessary to conduct the study at the investigator’s hospital, 
written documentation from the investigator is required. However, when the sponsor is responsible for EC 
submission/notification, a written documentation from the sponsor is required. 
For the initial submission and any subsequent CIP amendment, the investigator needs to sign a statement 
(available at Appendix K.6) confirming that this approach is in accordance with local regulations prior to start 
patient enrollment. A copy of this statement needs to be forwarded to Medtronic prior to the start of patient 
enrollment.   
 
 Informed consent process 
If full Informed Consent (other than the Data Release Consent) is requested by local laws or by the EC/IRB, the 
investigator or authorized designee must obtain written informed consent from the subject and the process must 
be documented before any clinical study related activity takes place.  
 
A “Patient Informed Consent” document will be developed specifically for each country, approved by the EC/IRB 
in the local language.  
Well in advance of the consent discussion, the subject should receive the EC/IRB approved Patient Information 
and Informed Consent Form. During the consent discussion, the investigator or his/her authorized designee must 
fully inform the patient of all aspects of the clinical study that are relevant to the patient’s decision to participate 
in the clinical study. All items addressed in the Patient Information and the Informed Consent Form must be 
explained. The language used shall be as non-technical as possible and must be understandable to the patient.  
The patient must have ample time and opportunity to read and understand the Patient Information and the 
Informed Consent Form, to inquire about details of the clinical study, and to decide whether or not to participate 
in the clinical study. All questions about the clinical study should be answered to the satisfaction of the patient. 
Neither the investigator, nor the investigation site staff shall coerce or unduly influence a patient to participate or 
to continue to participate in the clinical study. The informed consent process shall not waive or appear to waive 
the patient’s rights. 
When the patient decides to participate in the clinical study, the Informed Consent Form must be signed and 
personally dated by the patient and investigator or authorized designee. 
After all persons have signed and dated the Informed Consent Form, the investigator must provide the subject 
with a copy of the Patient Information and the signed and dated Informed Consent Form. 
The clinical study data can only be submitted to Medtronic upon fully execution of the Patient Informed Consent 
Form.  
The signed consent forms will be retained by the investigator and made available (for review only) to the study 
monitor and inspector or auditor on request.  
 Revisions in Patient Information and Informed Consent Form 
Medtronic will inform the investigators whenever new information becomes available that may be relevant to the 
subject’s confirmed participation in the clinical study. The investigator or his/her authorized designee should 
inform the subject in a timely manner.  
Medtronic will revise the written Patient Information and Informed Consent Form whenever new information 
becomes available that may be relevant to the subject’s confirmed participation in the clinical study. The revised 
information will be sent to the investigator for approval by the EC/IRB if applicable. After approval by the EC/IRB, 

 
 
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a copy of this information must be provided to the participating subjects, and the informed consent process as 
described above needs to be repeated. However, in case the revised Informed Consent has no impact on 
previously enrolled patients, the Informed Consent won’t need to be re-signed by already enrolled patients.   
 Data Release Consent process 
If Data Release Consent is requested by local laws or by the EC/IRB, the investigator or authorized designee must 
obtain written Data Release Consent from the patient and the process must be documented prior to releasing any 
personal information of the patient. 
During the consent discussion, the investigator or his/her designee must fully inform the patient of the clinical 
study in a non-technical wording understandable for the patient.  
The patient must have ample time and opportunity to inquire about details of the clinical study, and to decide 
whether or not to participate in the clinical study. All questions about the clinical study should be answered to the 
satisfaction of the patient.  
When the patient decides to participate in the clinical study, the written Data Release Consent form must be 
signed and personally dated by the patient and the investigator. 
After all persons have signed and dated the Data Release Consent Form, the investigator must provide the patient 
with a copy of the signed and dated Data Release Consent form.  
The clinical study data can only be submitted to Medtronic upon fully execution of the Data Release Consent Form.  
 Regulatory notification / approval 
The need for regulatory notification or submission is country-specific. The Medtronic study team will work 
together with the Medtronic regulatory department to identify the requirements per country.  
In countries where submission to the regulatory authority is required per local law, no patients will be enrolled in 
the clinical study until the particular regulatory authority has approved the current Clinical Investigation Plan of 
the clinical study and other documents as required according to the local requirements. 
 
D.3 Regulatory compliance 
This clinical study will be conducted in compliance with the Declaration of Helsinki 2013, laws and regulations of 
the country/ies in which the clinical study is conducted, including data protection laws, the Clinical Investigation 
Agreement and the Clinical Investigation Plan.  
All principles of the Declaration of Helsinki have been implemented in this clinical study by means of the patient 
informed consent process, EC/IRB approval (if applicable), clinical study training, clinical trial registration, 
preclinical testing, risk benefit assessment, publication policy, etc.  
All Medtronic Devices to be used in this study will be used within their intended use as described in the manual 
and Instructions for Use for which Medtronic obtained regulatory market release e.g. CE Marking in Europe. All 
Devices that can be used in this study are listed in section A.2. 
Only legally competent patients will be included in this post market release study.  
If the regulatory authority and/or EC/IRB imposes any additional requirements (e.g. safety reports, progress 
reports etc.), Medtronic will prepare the required documents and send them to the respective authority and/or 
EC/IRB. If any action is taken by a EC/IRB with respect to the investigation, the information will be forwarded to 
the sponsor. 
 

 
 
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D.4 Training requirements 
Prior to investigation site activation or subsequent involvement in clinical study activities, Medtronic will provide 
clinical study training relevant and pertinent to the involvement of personnel conducting clinical study activities 
and investigator responsibilities. 
At a minimum, training will consist of the following items: 
- 
CIP overview and timeframes 
- 
Patient eligibility criteria 
- 
PIC/DRF procedure and documentation in the patient’s medical record,  
- 
Consecutive enrollment-screening log 
- 
AE reporting 
- 
Source document requirements 
- 
Use of data collection tools ( EDC training) 
- 
Applicable local regulations 
- 
Collect ODI questionnaire in an independent way without influencing the patients.  
 
Performed training will be documented prior to investigation site activation. 
After initial training, trained clinical site personnel can provide training to other clinical site study team members 
on study documents and processes on which they have already been trained on. All training must be 
documented. The name of each member of the investigational site team that attended the training session must 
be recorded as well. 
An investigator in this protocol is defined as a surgeon who is trained on the protocol training requirements and 
listed on the site delegation list.  
D.5 Site readiness 
Before a study site can enroll a subject or have access to the electronic data capturing (EDC) system, the 
investigator must be in receipt of an ‘activation letter’ (this may also be an email) from Medtronic. In addition, 
proper documentation must be in place before site activation, both at the participating site and at Medtronic, 
before subject enrollment begins.  
D.6 Study materials and study-specific equipment 
Medtronic will provide study materials such as the Investigator site file required to conduct the clinical study.  
Device accountability and traceability is not required for Post Market Release (PMR) studies. The Devices used in 
this study are commercially available. All Devices need to be purchased by the sites as routinely done. The Devices 
will be used within the intended approved indication (IFU). Existing approved procedures for commercial product 
regarding distribution, shipment, storage, handling, and return of these Devices will be followed. 
 
E 
STUDY METHODS 
All assessments to be done at the different time intervals are described in Table 2 
 
Table 3: Description of Procedures and Assessments at different time intervals 
Pre-operative visit 
(Baseline): 
 
• 
Written Patient Informed Consent /Data Release Form 
• 
Demographic data  
• 
Medical history 
• 
Work status  
• 
Pain medication 

 
 
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• 
VAS Back and leg pain 
• 
ODI 
• 
EQ-5D 
• 
Neurological status 
• 
AP & Lateral Radiographic Evaluation 
• 
Imaging (MRI and/or CT Scan) 
• 
Sagittal balance (in those sites where this assessment is Standard 
of care) 
• 
DN4 for back and DN4 for leg** 
Surgical procedure: 
 
• 
Surgery procedure data 
• 
Surgery time 
• 
Blood loss and Transfusion 
• 
Device Models 
• 
Adverse Events 
Hospital stay and 
discharge: 
(Surgery = Day 0) 
• 
Length of hospital stay (in days) 
• 
VAS Back and leg pain (at Day 2, the day the patient is considered 
recovered from the surgery(=SRD) and/or Day of discharge) 
• 
Time in days to first ambulation  
• 
Surgery Recovery Day 
• 
Record pain medication 
• 
Adverse Events 
Postoperative 
assessment at  
4w (±2w): 
3m (-1.5/+3m) 
 
• 
VAS Back and leg pain 
• 
ODI 
• 
EQ-5D 
• 
Neurological Status 
• 
Work Status and rehabilitation program 
• 
Pain medication  
• 
Adverse Events  
• 
Sagittal balance (in those sites where this assessment is standard 
of care)  
• 
DN4 for back and DN4 for leg (at 3m only)** 
Postoperative 
assessment at  
1, 2,3, 4 and 5y (±6m) 
• 
VAS Back and leg pain 
• 
ODI 
• 
EQ-5D 
• 
Neurological Status 
• 
Work Status and rehabilitation program 
• 
Pain medication  
• 
Adverse Events  
• 
Fusion Status * 
• 
Sagittal balance (in those sites where this assessment is standard 
of care) 
• 
DN4 for back and DN4 for leg (at 1 year only)** 
• 
CT-scan or alternatively an X-Ray will be taken to observe fusion 1 
year after the surgery. If no fusion is observed during the first fusion 
assessment further fusion assessment will be at the discretion of 
the investigator. 
• 
** As DN4 questionnaire has been added in the CIP amendment 2.0, 
the patients who were enrolled under CIP version 1.0 will NOT 
complete the DN4 retrospectively but will complete the DN4 
questionnaires for any upcoming follow up visits.  
 

 
 
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E.1 
Screening 
Every effort will be made to screen subjects consecutively for treatment and enrollment into the MASTERS-D 2 
global clinical study. Consecutive enrollment per procedure is essential in order to minimize selection bias.  
When all inclusion/exclusion criteria are fulfilled for a patient, then the patient should be enrolled in this study. 
Failure to meet all inclusion and exclusion criteria results in a screening failure and such subjects must not be 
enrolled to the study.  
A subject screening log is provided to the site and should be completed by the site’s study staff to maintain a 
cumulative log of all screened subjects per procedure. Patients not suitable for the study or refusal to participate 
should also be collected and reported in the subject screening log kept at each sites and reported at end of study 
recruitment. The Investigator will maintain a Subject Identification & Enrollment Log of all subjects enrolled in the 
clinical investigation, assigning a subject study ID linked to their names. Patient identifier will not leave the 
hospital. In case the group with one of the procedures is completed in a specific region, further enrollment of 
subjects into the procedure will be terminated, an email will be send to the participating sites when the enrollment 
for a specific procedure is complete. Once a procedure group is complete or the site maximum capacity of 
enrollment has been reached, no further screening will occur at the site for the applicable procedure.  
 
E.2 
Point of enrollment 
A subject is considered enrolled in this clinical study at the time at which he/she signed the Informed Consent 
Form or Data Release Consent form (whichever is applicable, see section D.2 Ethics).  
The investigator will maintain a log of all subjects enrolled in the clinical investigation, assigning an identification 
code linked to their names, alternative subject identification or contact information.  
All subjects must sign the Informed Consent Form or Data Release Consent form (whichever is applicable, see 
section D.2 Ethics) prior to undergoing any evaluations or procedures that are purely research-related (defined as 
those that would not be done if the subject was not participating in this study) or collection of study data.  
E.3 
Baseline procedures 
During the baseline visit the following data will be collected, patient demographics, medical history, comorbidities, 
surgery indication, pain medication, work status, imaging data. A standardized visual analogue scale (VAS, 0-10) 
will be used to evaluate the level of leg and back pain as perceived by the patient prior to surgery. Quality of life 
will be assessed having the patient completing the EQ-5D. Evaluation of how back or leg pain is affecting the 
patient’s ability to manage in everyday life will be assessed using the Oswestry Disability Questionnaire (ODI). 
Neurological status; in case of a neurological abnormality, the neurological status will be assessed and 
documented. The measurement of Slip and Disk Height of the levels adjacent to the index level(s) will be collected 
by X-Ray, CT scan and/or MRI whichever is applicable at the site. The identification of neuropathic pain will be 
assessed by the DN4 questionnaire in the back and in the leg. 
Sagittal Balance will be collected in those sites where it is standard of care by collecting an X-Ray (preferably this 
would be a long standing / full spine X-Ray (C7 + Femoral Head visible) or alternatively a short X-Ray with the 
femoral heads and top of lordotic segment visible).  
AEs should be collected after patient signed consent/data release form. 
E.4 
Implant or procedure aspects 
Patients will receive a single or double level instrumented fusion using a minimally invasive/MAST™ PLIF, TLIF, 
DLIF, OLIF, ALIF or MIDLF surgical procedure with a posterior fixation. The use of a posterior fixation system is 
mandatory in this study and will be either mini-open and/or percutaneous.  
Only those investigators with a documented experience of at least 30 minimal invasive procedures are allowed to 
perform the procedure of the subjects in this study.  
 

 
 
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It is recognized that the situation of a patient might change after enrollment. Due to investigator’s discretion a 
patient who was scheduled for a minimally invasive lumbar fusion procedure might receive an open procedure, 
might not be operated to treat the degenerative lumbar spine or might have a different procedure for other 
reasons.  
It is at the investigator discretion to decide before or during the surgery that the patient does no longer meet the 
eligibility criteria of the study to perform a Minimally Invasive Fusion Surgery. If this situation occurs this shall be 
documented on a study deviation eCRF (please see section E.11) and appropriate action should be taken (see 
section E.10) as well as a rationale for either continuing with the minimally invasive procedure, continuing with an 
open procedure or for discontinuation of the procedure and the study early termination form will be completed 
in the eCRF. 
 
E.5 
Post Procedure to Discharge 
All subjects will be assessed until discharge. Assessments are described in Table 2 . 
Day 2 after the procedure, at SRD and at discharge following assessments will be collected: 
Pain medication, VAS Leg and Back pain intensity scores, hospital data and AEs. 
E.6 
Follow up requirements.  
The schedule for patient assessments and follow-up visits after surgery (with required windows) will be 4 weeks 
(± 2 weeks), 3 months (-1.5/+3 month), 1 year (± 6 month), 2 years (± 6 month), 3 years (± 6 month), 4 years (± 6 
month), 5 years (± 6 month).  
After the closure of the 5 year follow-up visit window patients will be automatically considered as terminated from 
the study.  
All data will be collected via a secure web-based data entry system. 
Treatment outcomes in terms of how back or leg pain is affecting the patient’s ability to manage in everyday life 
will be assessed using the Oswestry Disability Questionnaire (ODI). Preferably, these ODI outcome measurements 
at 1, 3 months and 1, 2, 3, 4, 5 year follow up will be done by site staff different than the surgeon who operated 
the patient.  
A standardized visual analogue scale (VAS, 0-10) will be used to evaluate the level of leg and back pain as perceived 
by the patient. 
Quality of life will be assessed having the patient completing the EQ-5D. 
The identification of neuropathic pain will be assessed by the DN4 questionnaire in the back and in the leg at 3 
and 12 months follow up. 
The measurement of Slip and Disk Height of the levels adjacent to the fused level(s) and fusion will be collected at 
1 year follow up with either a CT scan or X-Rays. If no fusion is observed, 1 year after the surgery, further fusion 
follow up assessment will be at the discretion of the investigator. 
Neurological status will also be documented. This is an AE if the patient did not have a neurological abnormality 
before. 
Additional medical visits, Pain medication, work status and rehabilitation program will also be collected as part of 
overall patient follow up. 
Sagittal Balance will be collected in those sites where it is standard of care by collecting an X-Ray (preferably this 
would be a long standing / full spine X-Ray (C7 + Femoral Head visible) or alternatively a short X-Ray with the 
femoral heads and top of lordotic segment visible). 
 
Table 2 summarizes assessments and data (variables) to be collected in the electronic-CRFs throughout the study. 
 

 
 
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E.7 
Data collection requirements 
Table 2 summarizes what data will be collected prospectively within this study.  
After the surgery, regular patient follow up visits will be done to complete the Quality of Life questionnaires and 
to assess work status, and rehabilitation program.  
While a hospital visit is required for the 3 months (-1.5/+3 month) and 1 year (± 6 month) follow up; the 
Postoperative follow-up assessment at 4 weeks (± 2 weeks),  2 years (±6 months), 3 years (±6 months), 4 years, 
(±6 months), and 5 years (±6 months) can either be done through a patient visit at the hospital or by means of a 
phone call done by the investigator and/or authorized designee.  
The ODI outcome measurements are preferably done by site staff different than the surgeon who operated the 
patient. Training will be provided to the site to collect the ODI outcome measurements in an independent way 
without influencing the patients.  
Imaging is critical for assessing fusion. At 1 year follow up, each site should at least perform a CT scan or X-Rays 
per patient to assess fusion. If no fusion is observed, 1 year after the surgery, further fusion follow up assessment 
will be at the discretion of the investigator and the investigator will have the opportunity to enter this data in the 
CRF.  
Sagittal Balance will only be collected in those sites where it is standard of care to assess the sagittal balance of 
the patient. 
Calibration and maintenance of imaging equipment should be done according to the instructions of the 
manufacturer of the equipment and according to local protocols per Institution’s standards.   
 
Table 4: Summary of scheduled procedures and assessments  
Baseline 
Day of 
Surgery (D0) (2) 
Hospital Stay and Discharge 
(3) 
Follow up assessments 
D2 
SRD 
DIS 
4(±2)week 
 
3(-1.5/+3)month 
  1 year      (±6 
months) 
    2 year    (±6 
months)  
3 year    (±6 
months) 
4 year    (±6 
months) 
5 year    (±6 
months) 
Data Release Form OR 
Informed Consent Form 
X 
(1) 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Surgery Indication 
X 
 
 
 
 
 
 
 
 
 
 
 
Pain medication 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Imaging 
(X-Ray, 
MRI 
and/or CT Scan) 
X 
 
 
 
 
 
 
 
 
 
 
 
VAS (4) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ODI 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
EQ-5D 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
DN4 in the back and DN4 in 
the leg 
X 
 
 
 
 
 
X 
X 
 
 
 
 
Work status 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 

 
 
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  (1) Patient Informed Consent must be obtained prior to performing any study specific procedure  
  (2) Day ‘0’ (D0) is the day of the surgery, D1 is the first day after surgery, D2 the second and so on. 
  (3) SRD = Surgery Recovery Day; DIS = Day of Discharge 
  (4) VAS Intensity scores for Back and Leg pains. 
  (5) CT scan or X-Rays at 1 year follow up. If no fusion is observed at 1 year follow-up, it will be at the discretion of the investigator to 
follow up if fusion can be observed (only if standard of care at the site).  
  (6) Optional only if it is routine practice (standard of care) at the site  
E.8 
Source documents 
All source documents marked in the eCRFs should be located in the patient’s medical records (electronic, digital, 
or paper), i.e. hospital records, surgery reports, x-rays, MRIs, CTs or any other material that contains original 
information used for data collection including the documentation of the AEs and study worksheets completed by 
the investigator or site staff. Patient completed questionnaires will be considered as source data (i.e. VAS pain 
scores, ODI, EQ-5D, DN4 in the back and DN4 in the leg).  
The investigator will clearly mark the medical records to indicate that the subject is enrolled in this clinical study.  
For studies conducted in Sweden the investigator should also provide a short explanation on the clinical study (i.e. 
post market release study with MAST and CD horizon spinal system, treatment: minimally invasive lumbar 
interbody fusion (1 or 2 level) and 5 years follow-up) in the patient medical records. 
In case a follow-up has been performed by phone, the site personel needs to record at a minimum the date of 
contact in the patient’s medical records, the occurrence or absence of any AEs, pain medications for the lumbar 
spine and any other pain medications and indicate on the questionnaires who was the person that completed 
them. 
In section F.1.2 it is described which source data can be recorded directly on the electronic Case report Forms.  
Access to all (including electronic) source documents (medical records and other source data) will be provided to 
the sponsor and its representatives, EC/IRB, regulatory authorities, if required.  
E.9 
Adverse events  
All AEs, regardless of relatedness to surgical procedure or outcome, should be reported throughout the study in 
the CRF and should be made available to the Medtronic study team. If applicable, these events will be reported to 
other countries where studies are conducted with the same or a similar product. All AEs will be screened 
immediately for possible product complaints, to allow compliance with the 48-hours reporting requirement.  
In China, the Clinical safety reporting requirements are governed by the following China Food and Drug 
Administration (CFDA) documents.  
- 
CFDA Notice No. 766: Measure on Medical Device Adverse Events Monitoring and Reevaluation 
- 
CFDA Guidance document No. 425: Device Adverse Event Monitoring (Interim)  
 
CFDA Notice No. 766 and CFDA Guidance document No. 425 are vigilance reporting requirements in China. 
Rehabilitation Program 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Neurological status 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X-Ray or CT Scan (5) 
 
 
 
 
 
 
 
X  
(X)  
(X)  
(X)  
(X)  
Sagittal Balance(6) 
(X)  
 
 
 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Surgery and hospital data 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
 
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Since there is no country specific clinical safety reporting requirement for this study in China, the common safety 
reporting process for all participating regions/countries will be followed in China. 
 
In Korea, The clinical safety and vigilance reporting requirements are governed by the following MFDS’s (The 
Ministry of Food and Drug Safety) documents. 
- 
MFDS Notification 2014-178 (Revised on Oct 31, 2014): Regulations for Approval of Clinical Trial Plan. 
- 
Ministerial Decree No.1307 (Effective on Jul 29, 2016): Enforcement Regulations of the Medical Device Act 
including KGCP 
- 
MFDS Notification No.2016-2 (Revised on Jan 14, 2016: Regulations on - Management of Medical Device 
Safety Information, Including Adverse Event Report. 
 
 Adverse Events and Device Deficiencies 
E.9.1.1 
Definition/classification  
For the purposes of the clinical report, each AE will be classified according to ISO 14155:2011 definitions and are 
provided in table 4. 
Where the definition indicates “device”, it refers to any device used in the study. This might be the device under 
investigation, or any market released component of the system.  
 
Table 5: Adverse Events Definitions 
ISO Definitions for Clinical Investigations of Medical Devices for Human Subjects 
Adverse Event (AE): (ISO14155:2011 3.2) 
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. 
 
For Korea: Under KGCP Article 2 item 12, this definition is equivalent to the definition of Adverse Event 
Adverse Device Effect (ADE): (ISO14155:2011 3.1) 
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 
 
For Korea: Under KGCP Article 2 item 13, this definition is equivalent to the definition of Adverse Device Effects. 
Unexpected Adverse Device Effects (UADE): (applicable for Korea only: KGCP Article 2 item 15) 
Adverse device effects showing differences in degree or severity from medical device-related information, 
including Investigator’s Brochure or attached documents to medical devices 
Serious Adverse Event (SAE): (ISO 14155:2011 3.37) 

 
 
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An 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 foetal distress, foetal 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. 
 
For Korea: Under KGCP Article 2 item 14, this definition is equivalent to the definition of Serious AE or ADE. 
Serious Adverse Device Effect (SADE): (ISO 14155:2011 3.36) 
Adverse device effect that has resulted in any of the consequences characteristic of a Serious Adverse Event.  
 
For Korea: Under KGCP Article 2 item 14, this definition is equivalent to the definition of Serious AE or ADE. 
Unanticipated Serious Adverse Device Effect (USADE): (ISO 14155:2011 3.42) 
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. 
 
Device deficiency: (ISO 14155:2011 3.15) 
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 labelling. 
 
Unavoidable AE 
An Adverse Event inherent to a surgical procedure that is expected to occur in all subjects for a 
projected duration. 
Event Description 
Timeframe (hours) from the Surgical Procedure 
Anesthesia related nausea / vomiting 
24 
Low-grade fever (<100°F or 37.8°C) 
48 
Sleep problems (insomnia) 
72 
 
In all geographies unavoidable AEs need not be reported unless the AE worsens or is present outside the stated 
timeframe post-implant. An event is not considered an AE if it has been identified as a pre-existing condition, 
unless the AE worsens or is present outside the stated post-Surgical Procedure timeframe.  
 
In addition, further classification of the relationship will be done by the investigator according to the following 
parameters: 
• Device related: 
Events specifically related to the Devices (please see definition of AEs and Device Deficiency in Section E.9.1) 
including but not necessarily limited to insertion device breakage, insertion device dysfunction, cage movement-

 
 
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migration, subsidence, screw breakage, screw pullout, screw dislodgement, rod breakage and 
inflammatory/allergic reaction to the Devices. 
• MAST™ Approach/Procedure related: 
Events specifically related to the minimally invasive surgical approach procedure including the minimally invasive 
access approach, decompression, and insertion of instrumentation. These events include but are not limited to 
local, temporary back pain caused by ligament distraction, dural tears, nerve root injury and bone fracture.  
• General Surgery related or Lumbar Fusion procedure related: 
Events related to general surgery in general who are not related to the MAST related events. These events could 
include but are not limited to, hematoma, wound pain, wound breakdown and infection.  
• Related to the disease: 
AEs related to the progression of degenerative lumbar spine. These events include but are not limited to 
recurrence of symptoms due to further degeneration of a previously healthy level leading to symptoms occurrence. 
 
AE not related to diseases should be collected as well. 
 
The above relationship parameters will be assessed and categorized as per the MEDDEV 2.7/3 levels of causality:  
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 serious 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; 
- 
the event involves a body-site or an organ not expected to be affected by the device or procedure; 
- 
the serious 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 serious 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 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; 

 
 
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- 
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; 
- 
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 serious event. 
E.9.1.2 
 Recording and reporting of Adverse Events 
In this study all AEs will be collected. The AE information will be collected throughout the study and reported to 
Medtronic on an electronic AE Form in the eCRF, one for each AE. See the AE eCRF for the information to be 
reported for each AE.  
For AEs that require immediate reporting (see Table 5: Adverse Event reporting requirements), initial reporting 
shall be done by completing the appropriate eCRF. If the eCRF is not available reporting may be done by phone or 
e-mail (see section E.9.3 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact details).  
 
In case the investigator requires information from the sponsor in an emergency situation, the investigator can 
contact the Medtronic contacts available in the Investigator Site file. Contact details of the Study Team members 
are also given in section E.9.3 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact details 
The preferred way of transmission AEs and DDs is the Oracle Clinical (eCRF) system, but in case the eCRF cannot 
be accessed, the investigator can contact the below mentioned Medtronic personnel (preferably per email). 
Contact details available in the Investigator Site file:  
a. Your local clinical contact person (monitor) 
b. Clinical Study Manager 
c. 
Clinical Safety Specialist 
 
In case email is used to inform the Medtronic personnel, the AE / DD worksheet that can be found in the patient 
binders may be used for completion of available information, preferably signed by investigators and attached to 
the email.  
 
The same CIP reporting timelines apply for all types of reporting as if the eCRF would be available. 
 
E.9.1.3 
Recording and reporting of Device Deficiencies 
Device Deficiency information will be collected throughout the study and reported to Medtronic. Device 
Deficiencies that did not lead to an AE should be reported on a Device Deficiency Form in the eCRF, one for each 
Device Deficiency.  

 
 
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See the Device Deficiency eCRF for the information to be reported for each Device Deficiency that did not lead to 
an AE.  
 
Device deficiencies that did not lead to an AE but could have led to an SADE 
a) if either suitable action had not been taken, 
b) if intervention had not been made, or 
c) if circumstances had been less fortunate, 
require immediate reporting (see Table 5: Adverse Event reporting requirements). Initial reporting shall be done 
by completing the appropriate eCRF. If the eCRF is not available reporting may be done by phone or e-mail (see 
section E.9.3 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact details).  
 
E.9.1.4 
 Adverse Event and Device Deficiency review process 
All AEs and Device Deficiencies will be reviewed by the Medtronic Safety Representative. This review will include 
the determination whether the AE/Device Deficiency meets regulatory reporting requirements (see Table 5: 
Adverse Event reporting requirements). The sponsor will ensure timely AE/Device Deficiency reporting to meet 
global regulatory requirements.  
A list of anticipated AEs that may be expected in nature can be found in the IFU of the used devices.  
 
Table 6: Adverse Event reporting requirements 
AE reporting requirements  
Serious Adverse Device Effects (SADE), including Unanticipated Serious Adverse Device Effect (USADE): 
Investigator submit to: 
 
Medtronic 
Immediately (within 3 calendar days) after the investigator first learns 
of the event or of new information in relation with an already 
reported event.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Korea: SADEs and USADEs causing death or life threatening must be 
reported within 7 calendar days from the date when the investigator 
had relevant effects reported or informed. In this case, the 
investigator shall make a detailed report of the SADEs, USADEs causing 
death or life threatening within 8 calendar days from the initial report. 
SADEs and USADEs excluding death or life threatening must be 
reported within 15 calendar days from the date when the investigator 
had relevant effects reported or informed. (KGCP Article 8 item 18) 
All other geographies: Submit to EC/IRB per local reporting 
requirement. 
Sponsor submit to: 
 
Regulatory Authorities  
Korea: SADEs and USADEs causing death or life threatening (including 
any oversea events) must be reported by the Korea Quality Team to 
the Medical Device Safety Bureay at MFDS within seven (7) calendar 
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informed. In this case, the sponsor shall make a detailed report of the 
SADEs, USADEs causing death or life threatening within eight (8) 
calendar days from the initial report. Other SADEs and USADEs 
excluding death or life threatening (including any oversea events) 
must be reported within fifteen (15) calendar days from the date when 
the sponsor had relevant effects reported or informed.  
(KGCP Article 8 item 18) 
All other geographies: Reporting timeframe as per local requirement. 
EC/IRB 
Korea: SADEs and USADEs causing death or life threatening (including 
any oversea events) must be reported by the Korea Quality Team to 
the IRB* and investigators within seven (7) calendar days from the 
date when the sponsor had relevant effects reported or informed. In 
this case, the sponsor shall make a detailed report of the SADEs, 
USADEs causing death or life threatening within eight (8) calendar days 
from the initial report. Other SADEs and USADEs excluding death or 
life threatening (including any oversea events) must be reported 
within fifteen (15) calendar days from the date when the sponsor had 
relevant effects reported or informed. (KGCP Article 8 item 18) 
* The reporting to the IRB is applicable only if the PI failed to report to 
the IRB, or what was reported by the PI needs to be changed. 
All other geographies: Submit to EC/IRB per local reporting 
requirement. 
Serious Adverse Events (SAE) 
Investigator submit to: 
 
Medtronic 
Korea: The PI shall quickly report all SAEs (excluding what is classified 
in the protocol as ones not requiring immediate reporting) as 
expedited reports of adverse device effects under Attached Form No. 
35 to the sponsor within the period provided in the protocol. (KGCP 
Article 7 item 11) It is recommended for the investigator to report 
safety events as soon as possible but no longer than 15 calendar days. 
 
Mexico: Investigators must inform the study monitor/sponsor on the 
same day as they have knowledge of the event. 
 
All other geographies: Immediately (within 3 calendar days) after the 
investigator first learns of the event or of new information in relation 
with an already reported event.  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities  
Reporting timeframe as per local requirement. 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 

 
 
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Adverse Device Effects (ADE) 
Investigator submit to: 
 
Medtronic 
Immediately (within 3 calendar days) after the investigator first learns 
of the event).  
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
All other AEs 
Investigator submit to: 
 
Medtronic 
Submit (within 20 calendar days) after the investigator first learns of 
the event. 
Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Device Deficiencies with SADE potential 
Investigator submit to: 
 
Medtronic 
Mexico: Investigators must inform the study monitor/sponsor on the 
same day as they have knowledge of the event. 
 
All other geographies: Immediately (within 3 calendar days) after the 
investigator first learns of the deficiency or of new information in 
relation with an already reported deficiency.  
Regulatory 
Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
All other Device Deficiencies 
Investigator submit to: 
 
Medtronic 
Submit (within 20 calendar days) after the investigator first learns of 
the deficiency. 

 
 
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Regulatory Authority 
As per local reporting requirement.  
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Refer to APAC addendum for reporting in APAC region. 
 
E.9.1.5 
Reporting of product complaints 
Product Complaint: Any written, electronic or oral communication that alleges deficiencies related to the identity, 
quality, durability, reliability, safety, effectiveness or performance of a medical device that has been placed on the 
market. 
 
All devices used in this study are market released. Therefore, vigilance and Medical Device Reporting (MDR) 
reporting is applicable and AEs related to any market-released device during the study must be reported. The 
reporting of product complaints is not part of the clinical study and should be done in addition to the Adverse 
Event reporting requirements. Refer to local regulations for reporting requirements.  
 
It is the responsibility of the investigator to report all product complaint(s) associated with a medical device 
distributed by Medtronic, regardless whether they are related to intended use, misuse or abuse of the product. 
Reporting must be done immediately and via the regular channels for market-released products.. 
 
In case the AE is related to a non-Medtronic market released device used during the study, post market 
surveillance is also applicable and the investigator is responsible for immediate reporting of the product complaint 
via the regular channels for market released products. 
 
Medtronic will notify the regulatory authorities (e.g. Competent Authority) if a complaint meets the criteria of 
AE reporting according to local requirements. Besides the data on the Case Report Forms, imaging data from 
MRI, CTs , X-Rays and/or medical records may also be collected for additional assessment.  
 
 Adverse Event Advisory Committee 
No AEAC committee will be installed for this PMR study.  
 
 AE/DD reporting in case eCRF cannot be accessed and/or emergency contact details 
The preferred way of transmission AEs and DDs is the Oracle Clinical (eCRF) system, but in case the eCRF cannot 
be accessed, the investigator can contact the below mentioned Medtronic personnel (preferably per email). 
Contact details available in the Investigator Site file:  
a. Your local clinical contact person (monitor) 
b. Clinical Study Manager 
c. 
Clinical Safety Specialist 
 
In case email is used to inform the Medtronic personnel, the AE / DD worksheet that can be found in the patient 
binders may be used for completion of available information, preferably signed by investigators and attached to 
the email.  
 

 
 
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The same CIP reporting timelines apply for all types of reporting as if the eCRF would be available. 
E.10 Subject accountability 
Patients may withdraw from the study at any time and for any reason. Stop of data collection for patients in the 
study may occur in the following cases: 
- Withdrawal of consent by patient 
- Patient lost-to-follow-up 
- Patient death 
- Patient did not undergo the instrumented lumbar fusion as defined in this protocol 
If a patient is withdrawn from the study, the reason for withdrawal shall be recorded in the eCRF and in the 
subject’s hospital record. Subjects withdrawn from the study will only be replaced when patients did not 
undergo the instrumented lumbar interbody fusion with posterior fixation as defined in this protocol and if the 
enrollment is still open. In that case only, these patients will not contribute to the site and region specific 
enrollment limits nor to the maximum amount of patient enrollments per procedure. 
Compliance to the minimum recommended follow-up schedule is essential to enable the analysis of the results 
in a scientifically sound and meaningful way. If, for whatever reason, the patient follow-up cannot be scheduled 
within the time window or occurred outside the time window, it is still essential to schedule a follow-up visit and 
to document the patient data at a date as close as possible to the calculated follow-up date.  
Patients that are lost-to-follow-up should be avoided as much as possible and investigators are urged to do their 
utmost best to maintain patient’s follow-up compliance as per CIP. 
 
Withdrawal of consent: 
Subjects may withdraw from the study at any time and for any reason. If a subject withdraws from the study, the 
Investigator will document the reason for withdrawal, if given by the subject, in the source documents and in the 
subject’s CRF. Subjects withdrawn from the study will not be replaced. The follow up of these subjects will be 
according to the standard of care at the site. 
 
Lost to follow up: 
Before considering a patient as lost to follow up, the Investigator should make any attempt to contact the subject 
(or relevant other persons associated with the subject) to have the subject return for follow-up to determine their 
clinical status and the occurrence/resolution of AEs, if any.  
 
Before documenting a subject as lost to follow up, the Investigator should document in the CRF and source 
documents at least 3 contact attempts with the subject, subject’s relatives or other persons associated with the 
subject. In addition, the investigator should make a reasonable effort to ascertain the reason(s), while fully 
respecting the subject's rights (e.g. if a patient is deceased, the date of death should be completed or if the subject 
is alive, the date of last contact with patient should be provided). 
E.11 Study deviations and CIP changes 
A study deviation is an event where the investigator or site personnel did not conduct the clinical study 
according to the Clinical Investigational Plan or Clinical Investigation Agreement. The investigator is not allowed 
to deviate from the above mentioned documents except under emergency circumstances to protect the rights, 
safety and well-being of human subjects. All deviations shall be documented and explained, regardless the 
reason for the deviation. 
 
In this post market release study with a prospective design Deviations are defined as deviations related to: 

 
 
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• 
Data Release or Patient Informed Consent procedure 
• 
Enrolled patient does not meet Inclusion/Exclusion criteria 
• 
Visit not done 
• 
Assessment(s) at the visit not performed 
• 
Visit outside the CIP defined visit window 
• 
Patient did not undergo the instrumented lumbar fusion as defined in this protocol 
• 
Improper SAE / ADE / SADE reporting (please see section Table 5 AEs of this CIP). 
- 
Any (U)(S)A(D)Es, Device Deficiencies with SADE potential and Serious Procedure related AEs, 
that are not reported timely 
- 
Any AE or device deficiency without (S)A(D)E potential that is not reported with 20 calendar days 
• 
EC/IRB approval not obtained, if required 
      
All deviations shall be recorded in the eCRF and those below require immediate actions to be taken in case of their 
occurrence: 
 
Table 7 Deviation - Actions overview table 
Deviation: 
Action: 
No Patient Data Release (or Informed 
Consent) form properly obtained before 
enrollment 
Stop data entry and take all necessary actions in order to 
obtain the document; if not obtained, data will not be 
analyzed. 
Complete the protocol deviation form in the CRF 
Enrolled patient does not meet 
Inclusion/Exclusion criteria 
 
Evaluate in-and exclusion criteria of study to prevent 
deviation from reoccurring.  
Complete the protocol deviation form in the CRF 
Visit not done  
Complete the protocol deviation form in the CRF 
Assessment(s) at the visit not performed 
Complete the protocol deviation form in the CRF 
Visit outside the CIP defined visit window 
 
Complete the protocol deviation form in the CRF 
Improper SAE / ADE / SADE reporting 
Report the event immediately according to Section E.9 
Adverse events of this CIP. 
Complete the protocol deviation form in the CRF 
EC/IRB approval not obtained, if required 
Do not enroll (or stop patient enrolment) and take all 
necessary actions in order to obtain the EC/IRB approval. 
Complete the protocol deviation form in the CRF 
Patient did not undergo the instrumented 
lumbar fusion as defined in this protocol 
Refer to section (E.10 Subject accountability) 
Complete the protocol deviation form in the CRF 
Medtronic will assess the significance of all deviations and evaluate the need to amend the Clinical Investigation 
Plan, to early terminate the investigation or site termination in case the deviations only relate to one site, in 
accordance with Medtronic SOPs. 
 Request for approval of study deviations 
This is a study conducted within the IFU of the used Devices and due to the nature of the Protocol Deviations as 
defined in the section above pre-approval for study deviations will not be applied in this post market release study.  

 
 
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In any situation during the conduct of this study the investigator shall exercise his/her judgment to always 
safeguard the subject’s interest independent whether the action to be taken will lead to a Protocol Deviation or 
not. The investigator shall report the deviation as soon as possible to Medtronic and the reviewing EC/IRB, if 
applicable. Medtronic will inform the regulatory authorities, if required. 
 Reporting requirements for study deviations 
The investigator shall adhere to EC/IRB requirements and procedures for reporting study deviations. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any additional 
corrective and/or preventive actions (e.g. amend the CIP, additional training, terminate the study, etc.). 
Repetitive or serious investigator compliance issues may result in the need to initiate a corrective action plan, 
and in some cases freeze enrollment or ultimately terminate the investigator’s participation in the clinical study. 
Medtronic will provide investigation site-specific reports to the investigators on a yearly basis summarizing 
information on deviations that occurred at the investigational site.  
 Amendments to the Clinical Investigation Plan 
The investigator will propose any appropriate modification(s) of the Clinical Investigation Plan or investigational 
device or investigational device use. Medtronic will review this proposal and decide whether the modification(s) 
will be implemented.  
Medtronic will submit any significant amendment to the Clinical Investigation Plan, including a justification for 
this amendment, to the appropriate regulatory authorities and to the investigators to obtain approval from their 
EC/IRB, if applicable. Administrative amendments to the Clinical Investigation Plan will be submitted to the 
EC/IRB and appropriate regulatory authorities for notification, if applicable. 
F 
QUALITY CONTROL PROCEDURES 
F.1 
Procedures for database management 
 Data collection 
The investigator must ensure accuracy, completeness and timeliness of the data reported in the CRFs and in all 
other required reports. Data reported on the CRFs which are derived from source documents must be consistent 
with the source documents and discrepancies need to be justified in the CRF. 
Only authorized persons can complete CRFs. CRFs shall be signed by investigators (physicians only) as specified 
on the Delegated Tasks List included in the Investigator Site File. 
The Electronic Data Capture (EDC) system maintains an audit trail on entries, changes or corrections in CRFs. If a 
person is only authorized to complete CRFs or make changes to an already signed CRF, the investigator shall re-
sign this CRF. 
Besides the data on the Case Report Forms, imaging data from MRI, CTs, X-Rays may also be collected for 
assessment by a qualified evaluator. 
 Source data to be directly recorded on the Case Report Forms 
The following data will be recorded directly on the CRF and is considered as source data: 
- 
Patient work status and rehabilitation program information 
- 
Patient neurological status 
In case data are collected additionally to CRF data such as the CT scan, these will be handled as source data.  
 Time windows for completion and submission of Case Report Forms 
Data collected on each patient will be recorded on a web-based electronic Case Report Form (eCRF).  

 
 
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As a guideline the eCRFs should be up-dated preferably within 20 working days after the data are available. 
Different timelines for AE reporting apply and are described in Table 5: Adverse Event reporting requirements.  
Instructions for proper completion of the CRF and how the web-based system should be used will be provided to 
the clinical site at the start of the study.  
 Data review and processing 
Data management will be done according to Medtronic SOPs and the Data Management Plan for this clinical 
study. These documents will be made available on request. 
All collected data will be reviewed for completeness, correctness and consistency. In case of issues, queries will 
be sent to the investigator to complete, correct or comment the data. 
Data stored electronically shall be maintained in accordance to Medtronic corporate policies and record 
retention schedule. 
F.2 
Monitoring procedures 
Monitoring visits will be conducted at the start, during and at the closure of the clinical study in accordance with 
Medtronic SOPs and the Monitoring Plan.  
Trained Medtronic personnel or delegates appointed by Medtronic may perform study monitoring at the study 
site in order to ensure that the study is conducted in accordance with the CIP, the Clinical Trial Agreement, and 
applicable regulatory and local requirements. Medtronic, or delegates, must therefore be allowed access to the 
subjects’ case histories (clinic and hospital records, and other source data/documentation) upon request as per 
the Patient Informed Consent/Data Release Form Research Authorization (where applicable) and Clinical Trial 
Agreement. 
 Site Initiation Visits 
Site Initiation Visits will be conducted for sites participating in this trial to ensure that protocol-related activities 
are conducted in compliance with this CIP. Site Initiation Visit activities may be performed on site or remotely, at 
the discretion of the Clinical Study Manager.  
 Interim Monitoring Visits 
During the interim monitoring visits it will be verified whether signed and dated Informed Consent Forms / Data 
Release Forms have been obtained from each subject before any clinical-study-related procedures are 
undertaken.  
For this study a risk-based monitoring will be applied. Frequency of monitoring visits, detailed in a separate 
monitoring plan, will occur based on subject enrollment, timing of subject follow up visits, number of subjects 
with completed follow-up visits, volume of eCRF, numbers of AEs and study deviations, duration of the study, 
study compliance, remote monitoring findings, findings from the previous monitoring visit and any suspected 
inconsistency in data that requires investigation or other relevant reason(s). The level of monitoring will be 
defined in the monitoring plan. 
  
Monitoring will be conducted to monitor compliance with the protocol and adherence to the data collection 
procedures, to assess the accuracy and completeness of submitted clinical data and to verify that records and 
documents are being properly maintained for the duration of the study. In case of an on-site monitoring visit, the 
monitor will perform source data verification by review of original patient documents. 
When source data verification is performed, the monitor must have direct access to original source 
documentation, certified copies of the original source must be provided, or supervised access in situations 
wheredirect access is not possible. 
If electronic source documentation is used at the site, the site must provide to the monitor: 

 
 
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1. Direct access to the electronic medical record(s), or direct access to the electronic medical 
record(s) by reviewing alongside appropriate study staff 
2. Certified copies of the electronic medical record 
A certified copy is a copy of original source documents or printout of original electronic source documents 
generated or produced by the clinical research site. It requires to be verified (as indicated by a dated signature of 
a member of the investigation site team with a statement that it is a true reproduction of the original source 
document) or generated through a site’s validated process.  It is possible to combine multiple pages (which were 
copied or printed) together and sign and date the top page with a comment that this is a true and complete 
reproduction of the original source documents. 
The monitor must verify that he/she has complete access to all original or certified copies of source 
documentation required for the study. 
 Close out visits (COV) 
Close Out phone call or on-site visits will be conducted for sites participating in this trial to ensure that protocol-
related activities are conducted in compliance with this CIP.  
The Investigator Site file will be reviewed for completeness however verification of individual regulatory 
documents may also be confirmed if noted in prior monitoring visits reports and do not necessarily need to be re-
reviewed during the Close-out Visit. 
Site Close out Visits may be performed on site or remotely, at the discretion of the Clinical Study Manager. The 
minimum activities required for the COV remain the same whether performed remotely or by visiting the site and 
will be documented on the Site Close Out report. 
It is expected that all sites will have a close-out visit; however, in rare cases where it is not reasonable or possible 
for a COV to occur, it is at the discretion of the Clinical Study Team designee and the Monitoring Manager to omit 
the closeout visit. The decision and rationale for omitting the visit should be documented by the Clinical Study 
Team designee, and the documentation should be filed in the Investigator’s file and the sponsor’s File. 
COV activities may be performed for individual trial sites prior to closure of the entire trial. 
 Accessibility of investigation site staff and study materials 
The principal investigator(s), his/her delegate(s) and the study coordinator(s) shall be accessible to Medtronic field 
personnel and the Clinical Study Manager. This accessibility is of particular importance for reviewing data in the 
Case Report Form (CRF). Direct access to patient medical files for source data verification (if applicable) will need 
to be granted and prepared prior to any monitoring visits. 
 Audits and investigation site inspections 
In addition to regular monitoring visits, Medtronic may conduct audits at participating investigation sites. The 
purpose of an audit is to verify the adequate performance of the clinical study related activities. Independent of 
the employees involved in the clinical study, regulatory authorities may also perform inspections at participating 
investigation sites. Any regulatory authority inspection announcements shall be forwarded immediately to the 
Clinical Study Manager. 
The investigator and/or institution shall permit Medtronic and regulatory bodies direct access to source data and 
documents, taking into account any restrictions due to local law, to perform clinical study-related monitoring, 
audits, EC/IRB review (if applicable), and regulatory inspections. 

 
 
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F.3 
Study suspension or early termination 
 Early study suspension or termination 
Medtronic or Regulatory Authority may decide to suspend or prematurely terminate the clinical study if interim 
analysis indicates that the results significantly differ from the clinical study objectives. If the clinical study is 
terminated prematurely or suspended, Medtronic shall promptly inform the clinical investigators of the 
termination or suspension and the reason(s) for this. The investigator shall then promptly inform the reviewing 
EC/IRB, if required and the study patients.  
 Early investigation site suspension or termination 
Medtronic, EC/IRB or Regulatory Authority may decide to suspend or prematurely terminate an investigation site 
(e.g. in case of expiring approval of the reviewing EC/IRB, non-compliance to the Clinical Investigation Plan or lack 
of enrollment). If an investigation site is suspended or prematurely terminated, Medtronic shall promptly inform 
the investigator(s) of the termination or suspension and the reason(s) for this. The investigator shall then promptly 
inform the reviewing EC/IRB, if required and the study subjects or their legal representative. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of definite 
outcomes, investigators must assess whether to continue, modify or immediately stop the clinical study in the 
respective investigation site and immediately inform the sponsor and EC/IRB, if applicable. 
 Subject follow-up in case of termination 
In case of early termination of the study, the patients will continue to be followed according to the routine 
practice of the site.  
 
F.4 
Study close out 
In case of close out the investigators will be notified and notification/report to EC/IRB and Regulatory Authority 
will be done, if required per local regulations.  
G DATA ANALYSIS AND REPORTING 
G.1 Analysis of clinical data 
For the purpose of the analysis, all subjects who are enrolled and undergo a minimally invasive lumbar fusion 
procedure will be included in the analyses. All the analyses will be based on observed data. No missing data will 
be imputed. 
 Analysis of Primary Endpoint 
To evaluate whether the primary endpoint improvement in ODI at 3 months is equivalent for the spondylolisthesis 
DDD subjects treated with anterolateral approaches and the ones treated with posterior approaches, the two-
sided 95% confidence interval for the mean difference of ODI improvement at 3 months will be calculated. If the 
95% CI is within the equivalent range of (-10, 10), then the primary objective is met. In addition, the paired t-test 
will be carried out for each group to see whether the ODI improvement at 3 months from baseline is significant. 
 
 Analysis of Secondary Endpoints 
For the first secondary objective, the similar method as the one outlined above for the primary endpoint will be 
used to assess whether the ODI improvement at 3 months is equivalent for the non-spondylolisthesis DDD subjects 
treated with anterolateral approaches and the ones treated with posterior approaches. 

 
 
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For secondary points ODI improvement at other follow-ups other than at 3-months visit; change of VAS back and 
leg pain intensity and EQ-5D at all follow-ups through 5-year visit, summary statistics will be provided and the 
paired t-test will be used to test whether the improvement at each follow-up from baseline is significant.  
 
The neurological success rate will be summarized at each follow-up. Overall neurological success will be defined 
as maintenance or improvement in all sections (motor, sensory, reflex, and straight leg raising) for the time 
period evaluated. In order for a section to be considered a success, each element in the section must remain the 
same or improve from the time of the baseline evaluation to the time period evaluated. Therefore, if any one 
element in any section does not stay the same or improve, then a patient will not be considered a success for 
neurological status. 
Time-to-event-analysis will be conducted for fusion success.  The fusion success rate will be summarized for 1, 2, 
3, 4, 5 -year follow-up, if applicable. If a subject shows fusion success at early timepoints and non-fusion at a later 
timepoint, the fusion status at all earlier time points should be considered as non-fusion. 
For 2-level subjects, fusion success will be defined as achieving fusion at both treated levels.  
For secondary surgery at index levels, secondary surgery at adjacent levels and AEs, survival analysis will be 
performed to estimate the cumulative event rate up to 5 years.  
 
Healthcare utilization will be measured with the following three cost components:  
(1) resources: procedure, length of hospital stay, additional medical visits (outpatient consultations, visits to 
primary care services, etc) 
(2) medications and  
(3) non-pharmacologic therapies: rehabilitation program 
 
For time needed for first ambulation and surgery recovery day, summary statistics for continuous variable will be 
provided by subgroups. 
 
The analyses for the primary endpoint and secondary endpoints outlined in secondary objectives 2 and 3 will be 
done for all subjects and the following subgroups: 
 
1) In DDD patients with spondylolisthesis with stenosis 
2) In DDD patients with spondylolisthesis but without stenosis 
3) In DDD patients with stenosis but without spondylolisthesis  
4) All patients not included in subgroup 1), 2), 3).  
 Additional Data Analysis  
 
For other measurements, continuous variables will be summarized using mean, standard deviation, median, 
minimum and maximum while the categorical variables will be summarized using frequency and percentage.  
 
Baseline information will be summarized for all DDD patients and by subgroups as outlined below and/or per 
surgical procedure (ALIF, OLIF, DLIF, PLIF, TLIF, MIDLF). 
1) In DDD patients with spondylolisthesis and stenosis 
2) In DDD patients with spondylolisthesis without stenosis 
3) In DDD patients with stenosis without spondylolisthesis  
4) All patients not included in subgroup 1), 2), 3).  

 
 
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Determining if there is a correlation between sagittal balance at baseline and the radiological findings and the clinical 
outcomes at the follow-up visit, in those sites where this assessment is standard of care. 
 
Several subgroup analyses will be conducted based on DN4 scores (respectively for leg DN4 score and back DN4 score) 
at baseline, 3 months and 12-month visit. For subjects with baseline DN4 ≥ 4, the number and percentage of subjects 
with DN4 ≥ 4 or < 4 at 3 months and 12 months follow-up will be calculated and presented. Similarly for subjects with 
baseline DN4 < 4, the number and percentage of subjects with DN4 ≥ 4 or < 4 at 3 months and 12 months follow-up 
will be calculated and presented.  
  
In addition, ODI, EQ5D, VAS back and leg pain score at baseline, at each follow-up and the improvement of each 
variable from baseline at each follow-up will be presented by the subgroups defined by baseline DN4 scores and/or 
DN4 scores at follow-ups. Statistical comparison may be carried out for these subgroups. 
  
More subgroups analyses may be conducted as exploratory analyses by taking into consideration of pathology and 
surgical approach perspective. 
 
Any deviation(s) from the original statistical plan will be documented with a justification. 
 Interim Analysis 
In addition to a final statistical analysis, an interim analysis will be conducted when all subjects reached 3-month 
visit. At that time, the 3-month data including the primary endpoint improvement of ODI at 3-month visit from 
baseline will be finalized and the conclusion for the primary endpoint will remain unchanged at the final analysis. 
 
G.2 Publication Policy 
Publications and presentations referring to this clinical study will be coordinated by Medtronic to allow the use of 
all available data. The corporate publication policy will have to be adhered to by all participating investigation 
sites. 
Medtronic intends to submit the results of the clinical study in a scientific journal. In addition to the primary 
publication, interim reports could be prepared according to the publication plan.  
Authorship selection for publications using multi-center data will be determined based on the International 
Committee of Medical Journal Editors (ICMJE) published guidelines (JAMA 2013) and according to the criteria 
defined in the publication plan.  
In addition to the ICMJE guidelines, an author algorithm will be developed by Medtronic Spinal and Biologics (MSB) 
and approved by the Publication Committee. The algorithm will be used as a base to determine authorship for 
publications. This investigator credit system will focus on the enrollments and implants in total, but also includes 
data quality and active participation during the publication development. 
Due to the multicenter design of the study, one investigator per participating study site can be named as 
author or can be acknowledged in the paper.  
The number of authors will be dependent on the regulations of the target journal. Names of all participating 
principal investigators will appear in the Acknowledgement section of the publication. 
Subject to prior approval by the Advisory Committee: 
• 
Investigation site may access and use the data provided by itself for scientific publications  
• 
Pooling data from several investigation sites for publication purposes, national projects and 
international projects  
Medtronic as the owner of the data can use the data and/or any results derived from the data or publications 
based on that data for marketing purposes, further research and development of devices or educational use. 
The study sponsor will collect data in such way that no subject can be identified, and monitor study records. 

 
 
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Furthermore, the study is registered in a public database, on ClinicalTrials.Gov with the following identifier: 
NCT02617563. 
H MANAGEMENT 
H.1 Study staff 
A separate list with the study contacts and study monitors will be filed in the sponsor’s Project Files and the 
Investigator Site Files. The sponsor will keep this list up to date. 
H.2 Advisory committees 
 Advisory Committee 
During the start-up phase of the study, the MASTERS-D 2 Advisory Committee was established to perform one or 
more of the following:  
- 
To review the Clinical Study Protocol, and give feedback to Medtronic concerning the study design and 
scientific value of data collection;  
- 
To safeguard the interests of clinical study participants and monitoring the overall conduct and progress 
of the clinical study,  
- 
To evaluate the scientific validity and guide the development and timing of the publications and 
congress presentations (publication strategy), ensure compliance to ICMJE guidelines and Medtronic 
policy on publications. The members of the advisory committee are listed in the Appendix K.1. 
 
If needed, additional representatives and experts could be invited to support the activities of the MASTERS-D 2 
Advisory Committee. 
Reference is made to the MASTERS-D 2 Advisory committee Charter which is available upon request.  
 Data Monitoring Committee 
No Data Monitoring Committee will be installed for this clinical study as no interventions intended to prolong life 
or reduce risk of a major adverse health outcome (e.g., cardiovascular events) are evaluated, for which favorable 
or unfavorable study results suggest study termination. Nor are there safety concerns suggesting the need for a 
Data Monitoring Committee.  
 Publication Committee 
The advisory committee will perform publication committee duties. This committee will develop a final 
publication plan according to Medtronic Standard Operating Procedures. The publication plan will be defined 
during the course of the study and may be amended by the PC if additional conferences and journals are 
deemed appropriate. 
 
H.3 Records and reports 
 Investigator records 
At a minimum, the following records must be kept by the investigator:  
• 
Clinical Investigation Plan and, if applicable, any amendments 
• 
Medtronic and EC/IRB approved Patient Informed Consent/Data Release form 
• 
Regulatory Authority approval or notification, if applicable 

 
 
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• 
Fully signed clinical investigation agreement and confidentiality agreement (if not included in the 
clinical investigation agreement) 
• 
Completed Delegated Task List and Curriculum Vitae of all investigation site personnel (if applicable) 
• 
Training documentation of all investigation site personnel 
• 
Relevant communications 
• 
Subject screening log and/or subject identification log  
• 
Signed, dated and fully executed informed consent forms 
• 
Fully executed CRFs and corrections 
• 
Any other records that local regulatory agencies require to be maintained. 
 
 Investigator reporting responsibilities 
 
The investigator is responsible for the preparation and submission to the sponsor of all electronic case report 
forms (eCRFs). If any action is taken by an EC/IRB with respect to the study, the information must be forwarded to 
Medtronic. 
 
Table 8: Investigator Reporting Responsibilities Overview 
Report 
Submit to 
Description 
Premature termination or 
suspension of the study 
Medtronic and EC/IRB 
Provide prompt notification of termination or 
suspension and reason, in accordance with local 
regulations  
Study enrollment 
complete 
EC/IRB 
Provide notification that enrollment is completed, in 
accordance with local regulations 
Protocol Deviation 
Medtronic  
Complete the Protocol Deviations Forms in the eCRF 
Adverse events 
Medtronic 
Report according to reporting timelines provided in 
Table 5 
Final Report in accordance 
with local regulations 
EC/IRB 
Submit final report in accordance with local 
regulations. 
 
 Sponsor records 
At a minimum, the sponsor will keep the following records: 
• 
All essential study documents and correspondence that pertains to the clinical study 
• 
CIP and, if applicable, any amendments 
• 
Instructions for Use 
• 
Curriculum vitae of investigators and site staff 
• 
Delegated Task Lists and training records of investigators and site staff 
• 
EC/IRB approvals/notifications and regulatory approvals/notifications, if applicable 
• 
Signed Clinical Investigation Agreements and signed agreements with third parties 
• 
Shipping records for clinical-investigation related documents and materials 
• 
Medtronic and EC/IRC approved Patient Informed Consents/Data Release Forms 

 
 
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• 
Site selection reports, site initiation reports and monitoring visit reports  
• 
Adverse event and Device Deficiency reports 
• 
Fully executed CRFs and corrections 
 Sponsor reporting responsibilities 
Below Table 8 summarizes the sponsor reporting responsibilities to the EC/IRB or Regulatory Authorities that 
approved this clinical study 
 
Table 9: Sponsor Reporting Responsibilities Overview 
Report 
Submit to  
Description  
Adverse events 
Investigators,  
Relevant Authorities  
and EC/IRB  
Notification when appropriate (based upon 
perceived risk), and when required by 
relevant local authorities and EC/IRBs  
Premature termination 
or suspension of the 
study 
Investigators,  
Relevant Authorities  
and EC/IRB  
Provide prompt notification of termination 
or suspension and reason, according to local 
regulations  
Study enrollment 
complete 
Investigators,  
Relevant Authorities  
and EC/IRB upon request  
Medtronic will notify the investigators 
within 2 weeks of the completion of 
enrollment. Investigators will inform their 
EC/IRB, when required. Regulatory 
Authorities will be informed in accordance 
with local regulation.  
Final report 
Investigators,  
Relevant Authorities and 
EC/IRB upon request  
Medtronic will provide all investigators with 
a copy of the final report of the study. 
Investigators will submit the final report to 
their EC/IRB, if required. Regulatory 
Authorities will be informed in accordance 
with local regulation. 
 Record retention  
The investigator or the medical institution where the study was conducted must retain the Investigator Site File, 
patient medical files and CRFs in accordance with local law and regulations for a minimum period of 2 year (or 
longer if local laws require) after finalization of the clinical study report. In Europe, the documentation shall be 
kept for a period of at least 15 years after the clinical investigation with the device in question has ended. 
The investigator or the medical institution where the study was conducted should take measures to prevent 
accidental or early destruction of the clinical study related materials. 
 
H.4 Miscellaneous 
 Insurance 
The sponsor is a wholly owned subsidiary of Medtronic , 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 law and custom concerning specific insurance coverage. If required according to local 
regulations, a Clinical Trial Insurance statement/certificate will be provided to the EC/IRB. 

 
 
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 Subject compensation and indemnification 
As per UK research governance framework, indemnity arrangements will be put in place prior to the start of the 
study. For the other participating countries, local regulations to post market study requirements will apply and 
standard indemnity agreement is in place. 
 Subject confidentiality 
Subject confidentiality will be maintained throughout the clinical study to the extent permitted by law. That is, 
every attempt will be made to remove subject identifiers from clinical study documents. For this purpose, a unique 
subject identification code (site number and subject number) will be assigned and used to allow identification of 
all data reported for each subject. This will also ensure that the information can be tracked back to the source 
data. 
The sponsor, Medtronic, will collect this key-coded data and monitor study records. Third parties e.g. auditors, 
EC/IRBs, Governmental regulatory authorities may also have access to the study records. Participating patients 
will not be identified by name in any published reports about this study. 
 
I 
RISKS AND BENEFITS 
I.1 
Anticipated Clinical Benefits 
Patients will be submitted to a single or double level instrumented fusion procedure using PLIF,TLIF, ALIF, OLIF, 
DLIF or MIDLF techniques via a minimally invasive procedure and will receive the same medical treatment as if 
they would not participate in this study. 
Participation contributes to expand the knowledge base with respect to the minimally invasive procedures in a 
broad patient population. 
 
I.2 
Risks 
The investigator must continuously monitor, assess and document the risks (Declaration of Helsinki 2013). 
All devices used in this clinical study are released for distribution at the moment of clinical study start. Medtronic 
is not aware of any significant problems with this product. In the clinical study, the products will be used in 
accordance with their labeling; therefore no risks other than the risks typically associated with a routine device 
implantation and follow-ups are anticipated. Reference is made to the IFU for a detailed list of all risks 
associated with the devices.  
In addition subjects are treated according to general clinical practice. No additional risks are associated with 
participation in this clinical study.  
 
 

 
 
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J 
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K 
APPENDICES 
K.1 
Names and addresses 
 List of contact persons 
Sponsor:  
List of sponsor’s staff will be kept separate from the CIP and provided to the investigators. The sponsor will 
maintain an updated list. 
Advisory Committee Members 
The MASTERS-D 2 Advisory Committee in the therapeutic area of the minimally invasive lumbar fusion techniques 
for treatment of the degenerative lumbar spine consists of scientific experts. The list will be kept separately from 
the CIP.  
K.2 
Case Report Forms 
A copy of the CRF and amendments, if applicable, will be filed in the sponsor’s Project Files and the Investigator 
Site Files.  
K.3 
Sample Investigator Agreement 
A sample of the Investigator Agreement will be filed in the sponsor’s Project Files.  
 
K.4 
Abbreviations 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ALIF 
Anterior Lumbar Interbody Fusion 
APAC 
Asia Pacific  
ASD 
Adjacent Segment Disease 
BMI 
Body Mass Index (kg/m2) 
BRC 
Bakken Research Center 
CI 
Confidence Interval 
CIP 
Clinical Investigation Plan (‘Protocol’) 
CRF or e-CRF 
Electronic (Web Based) Case Report Form 
CT 
Computer Tomography 
CRO 
Clinical Research Organization 
DD 
 
Device Deficiency 
 
DDD 
Degenerative Disc Disease 
DLIF 
 
Direct Lateral Interbody Fusion 
 
DN4 
Douleur Neuropathique 4 (neuropathic pain) 
EC 
Ethical Committee 
EDC 
Electronic Data Capture 
FU 
Follow-up 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
LLIF 
Lateral Lumbar Interbody Fusion 

 
 
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MAST™ 
Minimal Access Spinal Technologies 
MIDLF 
Midline Lumbar Interbody Fusion 
MILIF 
Minimally Invasive Lumbar Interbody Fusion 
MRI 
Magnetic Resonance Imaging 
MIS 
Minimally Invasive Surgery 
ODI 
Oswestry Disability Index 
OLIF 
Oblique Lumbar Interbody Fusion 
DRF 
Data Release Form 
PIC 
Patient Informed Consent 
PLIF 
Posterior Lumbar Interbody Fusion 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SOP 
Standard operating procedure 
TLIF 
Transforaminal Lumbar Interbody Fusion 
VAS 
Visual Analogue Scale 
XLIF 
Extreme Lateral Interbody Fusion 
 
 
 
K.5 
Definitions 
 
Table 10: Definitions 
Open lumbar 
procedure : 
Surgical technique using a midline approach and requiring a partial or complete 
detachment of the lumbar fascia and paraspinal muscles to address the spinal 
pathology and placement of instrumentation. 
Minimally invasive 
procedure : 
Muscle sparing surgical technique using an inter-muscle or trans-muscle 
splitting approach, minimizing detachment of the lumbar fascia and paraspinal 
muscles to address the spinal pathology and placement of instrumentation. 
Definitions for instrumentation techniques : 
Mini-open 
technique : 
Instrumentation placement using direct vision of target structures via an inter-
muscle or trans-muscle splitting approach. 
Percutaneous 
technique : 
Instrumentation placement using radiographic or navigation guidance via stab 
incisions without direct vision of target structures. 
 
 
 

 
 
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K.6 
Sample Statement that no Ethics Committee approval is required 
 
MASTERS-D 2: A Prospective, 5-Year Global Study on MASTTM Minimally Invasive Fusion Procedures for the 
Treatment of the Degenerative Lumbar Spine.  
The purpose of this global study is to collect, in a consistent manner, demographic data, implant 
information and clinical data of patients who are planned to be submitted to single or double level 
instrumented posterior lumbar interbody fusion using a minimally invasive procedure. Patients will 
receive via a minimally invasive approach the CD HORIZON® Spinal System which is the main set of 
devices to be used in this study and consists of a variety of shapes and sizes of rods, hooks and screws 
that has the function to help provide immobilization and stabilization of spinal segments as adjunct to 
fusion. All Devices within the scope of this study shall be used within its intended use as described in 
the approved manual and Instructions for Use for which Medtronic obtained regulatory market release 
(for example CE Marking in Europe). 
Considering that the devices that will be used in this project have obtained regulatory market approval 
(e.g. CE Marking in Europe), and considering that for this study the patients will not necessitate any 
additional treatment other than the standard of care and will not expose patients to a higher risk, please 
check one as applicable: 
 
□ I declare that I have confirmed with my EC/IRB* that neither approval nor notification is required 
according to the local EC/IRB requirements for this project, and patient enrollment can start. This is 
in accordance with the country law on clinical research, and the hospital’s regulations. 
 
□ I declare that the EC/IRB has been notified about this project, and that according to the local EC/IRB 
requirements, patient enrollment can start. This is in accordance with the country law on clinical 
research, and the hospital’s regulations. 
 
Name:    ____________________________________________________________ 
 
Signature: ____________________________________________________________ 
 
Date:    _________________ 
 
Hospital:  ____________________________________________________________ 
 
 
*EC = Ethics Committee; IRB = Institutional Review Board;