ACDF: INFUSE® Bone Graft/ PEEK Interbody Spacer/ Anterior Cervical Plate Pivotal Clinical Trial

• Sponsor: Medtronic Spinal and Biologics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00485173
• Collaborator: (none)
• Enrollment: 224
• Locations: 16
• Arm: 1
• Duration (Months): 60
• Patients Per Site: 14
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of the investigational implant (INFUSE® Bone Graft/PEEK Interbody Spacer/Anterior Cervical Plate) as a method of facilitating spinal fusion at a single level from C3-C7 in patients with symptomatic cervical degenerative disc disease.

Condition or Disease	Intervention/Treatment	Phase
Degenerative Disc Disease	Device: INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate	N/A

Detailed Description

This pivotal clinical trial is being conducted to evaluate the safety and effectiveness of INFUSE® Bone Graft with the PEEK Interbody Spacer and Anterior Cervical Plate in patients with symptomatic cervical degenerative disc disease (DDD). The implant under investigation in this clinical trial is INFUSE® Bone Graft, the PEEK Interbody Spacer, and Anterior Cervical Plate. The device will be implanted using an anterior surgical approach. Safety and effectiveness data for patients in this study will be compared to that of historical controls. Historical control data will be taken from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).

Study Design

• Study Type: Interventional
• Actual Enrollment: 224 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pivotal Clinical Investigation of INFUSE® Bone Graft With a PEEK Interbody Spacer and an Anterior Cervical Plate in Patients With Cervical Degenerative Disc Disease at a Single Level.
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INFUSE® Bone Graft In this arm, patients will receive implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Device: INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate; All patients enrolled in this study will receive the investigational device.; Other Names: ACDF, Anterior Cervical Plate

Outcome Measures

Primary Outcome Measures

1. Rate of Overall Success [24 months post-operation]

   Rate of overall success is reported as the percentage of participants who met all of the following criteria: fusion at the treated level; pain/disability (Neck Disability Index) success; neurological status success; no serious adverse event classified as "implant associated" or "implant/surgical procedure associated;" no additional surgical procedure classified as a "failure."

Secondary Outcome Measures

1. Success Rate of Fusion [24 months post-operation]

   Success Rate of Fusion is reported as percent of participants who met the following fusion criteria: Evidence of bridging bone. This is based on the evidence of a continuous bony connection from the superior vertebral body to the inferior vertebral body in at least one of the following areas: lateral, anterior, posterior and/or through the PEEK spacer. No evidence of radiolucency at greater than 50% of the superior or inferior PEEK spacer-vertebra interface. No evidence of motion as defined by ≤ 4º of angular motion (based on flexion-extension lateral plain radiographs).

2. Success Rate of Neck Disability Index [24 months post-operation]

   Success rate of Neck Disability Index is reported as the percentage of participants whose neck disability index score met: Pre-treatment Score - Post-treatment Score ≥ 15.

3. Success Rate of Neurological Status [24 months post-operation]

   Success rate of neurological status is reported as the percentage of participants who met neurological success defined as maintenance or improvement in all sections (motor, sensory, and reflexes) 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 preoperative evaluation to the time period evaluated.

4. Neck Pain Success Rate [24 months post-operation]

   Neck pain success rate is reported as the percentage of participants whose neck pain improvement met: Preoperative Score - Postoperative Score > 0.

5. Arm Pain Success Rate [24 months post-operation]

   Arm pain success rate is reported as the percentage of participants whose arm pain improvement met: Preoperative Score - Postoperative Score > 0.

6. Success Rate of SF-36 PCS [24 months post-operation]

   Success rate of SF-36 Health Survey include two components: the success rate of a physical component summary (PCS) and the success rate of a mental component summary (MCS). The success rate of SF-36 PCS was defined as: Post Score - Pre Score >= 0.

7. Success Rate of SF-36 MCS [24 months post-operation]

   Success rate of SF-36 Health Survey include two components: the success rate of a physical component summary (PCS) and the success rate of a mental component summary (MCS). The success rates of SF-36 MCS were defined as: Post Score - Pre Score >= 0.

8. Operative Time [Time of operation, approximately 1.5 hrs.]

   Operative time was recorded from skin incision to wound closure.

9. Blood Loss [During the time of operation, approximately 1.5 hours.]

10. Hospital Stay [During the time of hospital stay, average of 1 day.]

11. Number of Patients Who Had Secondary Surgeries at the Index Level [24 months post-operation]

    Secondary surgical procedures at the index level included revisions, removal, supplemental fixation and reoperations.

Other Outcome Measures

1. Neck Disability Index Score [24 months post-operation]

   The self-administered Neck Disability Index (NDI) Questionnaire was used to assess patient neck pain and ability to function. The NDI scale ranges from 0-100. The best score is 0 (no disability) and worst is 100 (maximum disability).

2. Neck Pain Score [24 months post-operation]

   Numerical rating scales are used to evaluate neck pain intensity and frequency. Patients rate their neck pain intensity on a scale from 0-10, with a score of 0 representing "no pain" and a score of 10 representing "pain as bad as it could be." Similarly, patients record their neck pain frequency on a scale from 0-10, with a score of 0 being "pain none of the time" and a score of 10 being "pain all of the time." The total neck pain score is the sum of pain intensity and frequency scores.

3. Arm Pain Score [24 months post-operation]

   Numerical rating scales are used to evaluate arm pain intensity and frequency. Patients rate their arm pain intensity on a scale from 0-10, with a score of 0 representing "no pain" and a score of 10 representing "pain as bad as it could be." Similarly, patients record their arm pain frequency on a scale from 0-10, with a score of 0 being "pain none of the time" and a score of 10 being "pain all of the time." The total arm pain score will be the sum of pain intensity and frequency scores.

4. General Health Status -- SF-36 PCS [24 months post-operation]

   The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess general health status. The SF-36 results are summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for PCS is between 0 and 100, with higher scores denoting better quality of life.

5. General Health Status -- SF-36 MCS [24 months post-operation]

   The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess general health status. The SF-36 results are summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for MCS is between 0 and 100, with higher scores denoting better quality of life.

6. Ossification in the Region of Target Level [24 months post-operation]

   Ossification in the region of target level is reported as the percentage of the patients who had ossification in the region of the target level. The region of target level included the index level, the superior and inferior adjacent disc spaces, and the superior and inferior adjacent vertebral bodies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• INCLUSION:

1. Single-level cervical degenerative disc disease (from C3-C7) requiring surgical treatment and involving intractable radiculopathy and/or myelopathy.

2. Herniated disc and/or osteophyte formation at the level to be treated that is producing symptomatic nerve root and/or spinal cord compression.

3. Unresponsive to non-operative treatment for six weeks or has the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management.

4. At least 18 years of age and skeletally mature at the time of surgery.

5. A preoperative Neck Disability Index (NDI) score ≥30.

6. A preoperative neck pain score (pain intensity + pain frequency) ≥8 (out of 20) based on the preoperative Neck and Arm Pain Questionnaire.

7. If a female of childbearing potential, patient is not pregnant or nursing and agrees not to become pregnant for one year following surgery.

8. Is willing and able to comply with the study plan and able to understand and sign the Patient Informed Consent Form.

Exclusion Criteria:

• EXCLUSION:

1. A cervical spinal condition other than symptomatic cervical degenerative disc disease requiring surgical treatment at the involved level.

2. Documented or diagnosed cervical instability at the target level, defined by dynamic (flexion/extension) radiographs.

3. Previous surgical intervention at the involved level.

4. Any subsequent planned/staged surgical procedure at the involved or adjacent level(s).

5. Fused level adjacent to the level to be treated.

6. Severe pathology of the facet joints of the involved vertebral bodies.

7. Has osteoporosis, osteopenia, or osteomalacia as determined by DEXA scan.

8. Presence of active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin).

9. Overt or active bacterial infection, either local or systemic.

10. Insulin dependent diabetes.

11. Chronic or acute renal failure or prior history of renal disease.

12. Documented allergy or intolerance to stainless steel, titanium, titanium alloy, polyetheretherketone (PEEK), or tantalum.

13. Is mentally incompetent. (if questionable, obtain psychiatric consult.)

14. Is a prisoner.

15. Is an alcohol and/or drug abuser as defined by currently undergoing treatment for alcohol and/or drug abuse.

16. On oral or injectable steroids for 6 weeks or more at the time of enrollment.

17. A history of autoimmune disease.

18. History of exposure to injectable collagen or silicone implants.

19. History of hypersensitivity to protein pharmaceuticals (monoclonal antibodies or gamma globulins) or collagen.

20. Received any previous exposure to any/all BMPs either human or animal extraction.

21. History of allergy to bovine products.

22. History of any allergy resulting in anaphylaxis.

23. History of an endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis imperfecta).

24. Condition that requires postoperative medications that interfere with the stability of the implant, such as steroids.

25. Received treatment with an investigational therapy (drug, device, or biologic) within 28 days prior to implantation surgery or such treatment is planned during the 24-month period following the study surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	S & B Surgery Center	Beverly Hills	California	United States	90210
2	Orange County Neurological Association	Laguna Hills	California	United States	92653
3	Crane Creek Medical Ctr. The Back Center /Osler Medical	Melbourne	Florida	United States	32901
4	The Hughston Clinic, P.C.	Columbus	Georgia	United States	31908
5	University of Kansas Medcal Center	Kansas City	Kansas	United States	66160
6	Spine Institute	Shreveport	Louisiana	United States	71103
7	Springfield Neurological Institute	Springfield	Missouri	United States	65804
8	Buffalo Neurosurgery Group	West Seneca	New York	United States	14224
9	University of Cincinnati Dept of Neurosurgery	Cincinnati	Ohio	United States	45219
10	TriState Orthopedic Treatment Center	Norwood	Ohio	United States	45212
11	The Washington Hospital	Washington	Pennsylvania	United States	15301
12	Center for Sports Medcine & Orthopedics	Chattanooga	Tennessee	United States	37404
13	Semmes Murphey Neurologic & Spine Institute	Memphis	Tennessee	United States	38120
14	Central Texas Spine	Austin	Texas	United States	78731
15	Brain and Spine Center of Texas, L.L.P.	Plano	Texas	United States	75093
16	Inland Neurosurgery & Spine Associates, P.S.	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Medtronic Spinal and Biologics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medtronic Spinal and Biologics
• ClinicalTrials.gov Identifier: NCT00485173
• Other Study ID Numbers: INFUSE® Bone Graft PEEK ACDF
• First Posted: Jun 12, 2007
• Last Update Posted: Mar 19, 2013
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Intervertebral Disc Degeneration

Study Results

Participant Flow

Recruitment Details	Five subjects in investigational group and 4 subjects in control group died within 24 months postoperatively. Among them, however, one investigational subject who died at 20 months and one control subject who died at 23 months reported some data that were included as the 24-month evaluation. Thus, they were counted as evaluated at 24 months.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Period Title: Overall Study
STARTED	224	486
COMPLETED	188	422
NOT COMPLETED	36	64

Baseline Characteristics

Arm/Group Title	INFUSE® Bone Graft	Historical Control	Total
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).	Total of all reporting groups
Overall Participants	224	486	710
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (10.2)	44.2 (8.7)	45.0 (9.3)
Sex: Female, Male (Count of Participants)
Female	118 52.7%	251 51.6%	369 52%
Male	106 47.3%	235 48.4%	341 48%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	198 88.4%	447 92%	645 90.8%
Black	20 8.9%	18 3.7%	38 5.4%
Asian	2 0.9%	4 0.8%	6 0.8%
Hispanic	3 1.3%	13 2.7%	16 2.3%
Other	1 0.4%	4 0.8%	5 0.7%
Height (in.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [in.]	67.5 (4.2)	67.5 (4.0)	67.5 (4.1)
Weight (lbs.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lbs.]	188.8 (43.6)	182.5 (40.4)	184.5 (41.5)
Marital Status (participants) [Number]
Single	30 13.4%	61 12.6%	91 12.8%
Married	163 72.8%	373 76.7%	536 75.5%
Divorced	21 9.4%	44 9.1%	65 9.2%
Separated	7 3.1%	4 0.8%	11 1.5%
Widowed	3 1.3%	4 0.8%	7 1%
Education Level (participants) [Number]
< high School	10 4.5%	29 6%	39 5.5%
High School	80 35.7%	142 29.2%	222 31.3%
> high School	134 59.8%	314 64.6%	448 63.1%
Worker's Compensation (participants) [Number]
Yes	5 2.2%	46 9.5%	51 7.2%
No	219 97.8%	440 90.5%	659 92.8%
Unresolved Spinal Litigation (participants) [Number]
Yes	28 12.5%	38 7.8%	66 9.3%
No	196 87.5%	448 92.2%	644 90.7%
Tobacco Used (participants) [Number]
Yes	66 29.5%	145 29.8%	211 29.7%
No	157 70.1%	341 70.2%	498 70.1%
Alcohol Used (participants) [Number]
Yes	111 49.6%	150 30.9%	261 36.8%
No	113 50.4%	336 69.1%	449 63.2%
Preop Work Status (participants) [Number]
Yes	153 68.3%	309 63.6%	462 65.1%
No	71 31.7%	176 36.2%	247 34.8%

Outcome Measures

1. Primary Outcome

Title	Rate of Overall Success
Description	Rate of overall success is reported as the percentage of participants who met all of the following criteria: fusion at the treated level; pain/disability (Neck Disability Index) success; neurological status success; no serious adverse event classified as "implant associated" or "implant/surgical procedure associated;" no additional surgical procedure classified as a "failure."
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset (including all subjects who received study devices. Missing observations were not imputed.)

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	162	352
Number [percentage of participants]	80.9 36.1%	59.9 12.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority comparison of success rates in two treatment groups was a secondary objective of this trial. Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

2. Secondary Outcome

Title	Success Rate of Fusion
Description	Success Rate of Fusion is reported as percent of participants who met the following fusion criteria: Evidence of bridging bone. This is based on the evidence of a continuous bony connection from the superior vertebral body to the inferior vertebral body in at least one of the following areas: lateral, anterior, posterior and/or through the PEEK spacer. No evidence of radiolucency at greater than 50% of the superior or inferior PEEK spacer-vertebra interface. No evidence of motion as defined by ≤ 4º of angular motion (based on flexion-extension lateral plain radiographs).
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	160	345
Number [percentage of participants]	99.4 44.4%	87.2 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

3. Other Pre-specified Outcome

Title	Neck Disability Index Score
Description	The self-administered Neck Disability Index (NDI) Questionnaire was used to assess patient neck pain and ability to function. The NDI scale ranges from 0-100. The best score is 0 (no disability) and worst is 100 (maximum disability).
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	413
NDI at baseline	50.2 (14.3)	53.5 (16.2)
NDI at 24 months	14.6 (17.1)	20.9 (16.0)
NDI change at 24 months from baseline	-34.9 (17.3)	-32.3 (20.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	P-value was one-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Success Rate of Neck Disability Index
Description	Success rate of Neck Disability Index is reported as the percentage of participants whose neck disability index score met: Pre-treatment Score - Post-treatment Score ≥ 15.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	413
Number [percentage of participants]	85.8 38.3%	79.9 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random sampling, based on covariance matrix produced by logistic regression using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

5. Other Pre-specified Outcome

Title	Neck Pain Score
Description	Numerical rating scales are used to evaluate neck pain intensity and frequency. Patients rate their neck pain intensity on a scale from 0-10, with a score of 0 representing "no pain" and a score of 10 representing "pain as bad as it could be." Similarly, patients record their neck pain frequency on a scale from 0-10, with a score of 0 being "pain none of the time" and a score of 10 being "pain all of the time." The total neck pain score is the sum of pain intensity and frequency scores.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	175	413
Neck pain at baseline	15.9 (2.7)	15.8 (3.8)
Neck pain at 24 months	4.5 (5.2)	6.0 (6.9)
Neck pain change at 24 months from baseline	-11.2 (5.3)	-9.8 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	P-value was one-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Success Rate of Neurological Status
Description	Success rate of neurological status is reported as the percentage of participants who met neurological success defined as maintenance or improvement in all sections (motor, sensory, and reflexes) 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 preoperative evaluation to the time period evaluated.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	177	414
Number [percentage of participants]	93.8 41.9%	85.0 17.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

7. Other Pre-specified Outcome

Title	Arm Pain Score
Description	Numerical rating scales are used to evaluate arm pain intensity and frequency. Patients rate their arm pain intensity on a scale from 0-10, with a score of 0 representing "no pain" and a score of 10 representing "pain as bad as it could be." Similarly, patients record their arm pain frequency on a scale from 0-10, with a score of 0 being "pain none of the time" and a score of 10 being "pain all of the time." The total arm pain score will be the sum of pain intensity and frequency scores.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	175	413
Arm pain at baseline	13.5 (5.1)	14.8 (4.7)
Arm pain at 24 months	3.6 (4.9)	4.7 (5.8)
Arm pain change at 24 months from baseline	-10.1 (6.3)	-10.1 (6.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments	P-value was one-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Neck Pain Success Rate
Description	Neck pain success rate is reported as the percentage of participants whose neck pain improvement met: Preoperative Score - Postoperative Score > 0.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	175	413
Number [percentage of participants]	96.0 42.9%	92.7 19.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.414
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

9. Other Pre-specified Outcome

Title	General Health Status -- SF-36 PCS
Description	The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess general health status. The SF-36 results are summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for PCS is between 0 and 100, with higher scores denoting better quality of life.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	407
SF-36 PCS at baseline	31.6 (6.6)	31.9 (7.3)
SF-36 PCS at 24 months	47.7 (11.1)	45.3 (11.5)
SF-36 PCS change at 24 months from baseline	15.6 (10.9)	13.1 (11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments	P-value was one-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Arm Pain Success Rate
Description	Arm pain success rate is reported as the percentage of participants whose arm pain improvement met: Preoperative Score - Postoperative Score > 0.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	175	413
Number [percentage of participants]	90.9 40.6%	88.6 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

11. Other Pre-specified Outcome

Title	General Health Status -- SF-36 MCS
Description	The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess general health status. The SF-36 results are summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for MCS is between 0 and 100, with higher scores denoting better quality of life.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	407
SF-36 MCS at baseline	43.6 (12.0)	43.6 (12.1)
SF-36 MCS at 24 months	51.8 (9.5)	50.9 (10.8)
SF-36 MCS Change at 24 months from baseline	8.0 (12.0)	7.2 (13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.189
	Comments	P-value was one-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

12. Secondary Outcome

Title	Success Rate of SF-36 PCS
Description	Success rate of SF-36 Health Survey include two components: the success rate of a physical component summary (PCS) and the success rate of a mental component summary (MCS). The success rate of SF-36 PCS was defined as: Post Score - Pre Score >= 0.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	407
Number [percentage of participants]	89.8 40.1%	88.2 18.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.466
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

13. Secondary Outcome

Title	Success Rate of SF-36 MCS
Description	Success rate of SF-36 Health Survey include two components: the success rate of a physical component summary (PCS) and the success rate of a mental component summary (MCS). The success rates of SF-36 MCS were defined as: Post Score - Pre Score >= 0.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	176	407
Number [percentage of participants]	75.0 33.5%	71.3 14.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The predefined non-inferiority margin was 0.10.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was one-sided from random samplings, based on logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Superiority analysis was performed if non-inferiority was demonstrated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments	P-value was one-sided, obtained from logistic regression model by using propensity score as a covariate.
	Method	Regression, Logistic
	Comments

14. Secondary Outcome

Title	Operative Time
Description	Operative time was recorded from skin incision to wound closure.
Time Frame	Time of operation, approximately 1.5 hrs.

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	224	486
Mean (Standard Deviation) [hrs]	1.0 (0.5)	1.4 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was two-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

15. Secondary Outcome

Title	Blood Loss
Time Frame	During the time of operation, approximately 1.5 hours.

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	224	484
Mean (Standard Deviation) [ml]	40.1 (54.1)	58.4 (59.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was two-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

16. Secondary Outcome

Title	Hospital Stay
Time Frame	During the time of hospital stay, average of 1 day.

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	224	486
Mean (Standard Deviation) [days]	1.0 (0.7)	1.0 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.341
	Comments	P-value was two-sided, adjusted from ANCOVA with the propensity score as the covariate.
	Method	ANCOVA
	Comments

17. Secondary Outcome

Title	Number of Patients Who Had Secondary Surgeries at the Index Level
Description	Secondary surgical procedures at the index level included revisions, removal, supplemental fixation and reoperations.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	224	486
Number [participants]	6 2.7%	27 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.479
	Comments	P-value was two-sided, obtained from Cox regression and adjusted with propensity scores.
	Method	Regression, Cox
	Comments

18. Other Pre-specified Outcome

Title	Ossification in the Region of Target Level
Description	Ossification in the region of target level is reported as the percentage of the patients who had ossification in the region of the target level. The region of target level included the index level, the superior and inferior adjacent disc spaces, and the superior and inferior adjacent vertebral bodies.
Time Frame	24 months post-operation

Outcome Measure Data

Analysis Population Description

Primary dataset.

Arm/Group Title	INFUSE® Bone Graft	Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.	Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
Measure Participants	224	486
Preoperative (n=220, 442)	40.9 18.3%	36.9 7.6%
24 months (n=168, 407)	78.6 35.1%	59.2 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	INFUSE® Bone Graft, Historical Control
	Comments	Statistical analysis at 24 months postoperation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was from logistic regression model by using propensity score and any ossification 'Yes/No' at preop as the covariates.
	Method	Regression, Logistic
	Comments

Adverse Events

Time Frame	Up to 24 months
Arm/Group Title	INFUSE® Bone Graft		Historical Control
Arm/Group Description	In this arm, patients received implant with INFUSE® Bone Graft/PEEK Spacer/Anterior Cervical Plate.		Historical control was pooled from the control arms of the following Medtronic studies: (1) the Artificial Cervical Disc (also known as PRESTIGE® Cervical Disc System) pivotal IDE trial (NCT00642876) and (2) the BRYAN® Cervical Disc System pivotal IDE trial (NCT00437190).
All Cause Mortality
	INFUSE® Bone Graft		Historical Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	INFUSE® Bone Graft		Historical Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/224 (31.7%)		159/486 (32.7%)
Cardiac disorders
Acute Myoccardial Infarction	0/224 (0%)	0	2/486 (0.4%)	2
Angina Pectoris	0/224 (0%)	0	1/486 (0.2%)	1
Atrial Fibrillation	0/224 (0%)	0	1/486 (0.2%)	1
Atrial Flutter	0/224 (0%)	0	1/486 (0.2%)	1
Cardiac Arrest	1/224 (0.4%)	1	1/486 (0.2%)	1
Cardiogenic Shock	1/224 (0.4%)	1	0/486 (0%)	0
Cardiomegaly	2/224 (0.9%)	2	0/486 (0%)	0
Coronary Artery Disease	2/224 (0.9%)	2	0/486 (0%)	0
Myocardial Infarction	0/224 (0%)	0	1/486 (0.2%)	1
Palpitations	1/224 (0.4%)	1	0/486 (0%)	0
Supraventricular Extrasystoles	1/224 (0.4%)	1	0/486 (0%)	0
Ventricular Extrasystoles	1/224 (0.4%)	1	0/486 (0%)	0
Endocrine disorders
Autoimmune Thyroiditis	1/224 (0.4%)	1	0/486 (0%)	0
Hypothyroidism	1/224 (0.4%)	1	0/486 (0%)	0
Thyroid Cyst	0/224 (0%)	0	1/486 (0.2%)	1
Eye disorders
Astigmatism	1/224 (0.4%)	1	0/486 (0%)	0
Cataract	1/224 (0.4%)	1	1/486 (0.2%)	1
Ectropion	1/224 (0.4%)	1	0/486 (0%)	0
Lacrimation Increased	1/224 (0.4%)	1	0/486 (0%)	0
Visual Impairment	0/224 (0%)	0	1/486 (0.2%)	1
Gastrointestinal disorders
Abdominal Distension	0/224 (0%)	0	1/486 (0.2%)	1
Abdominal Hernia	1/224 (0.4%)	1	0/486 (0%)	0
Abdominal Pain	1/224 (0.4%)	1	1/486 (0.2%)	1
Abdominal Pain Upper	0/224 (0%)	0	1/486 (0.2%)	1
Crohn's Disease	0/224 (0%)	0	1/486 (0.2%)	1
Diarrhoea	0/224 (0%)	0	1/486 (0.2%)	1
Dysphagia	2/224 (0.9%)	2	1/486 (0.2%)	1
Gastrointestinal Ulcer	0/224 (0%)	0	1/486 (0.2%)	1
Haematochezia	1/224 (0.4%)	1	0/486 (0%)	0
Haemorrhoids	1/224 (0.4%)	1	0/486 (0%)	0
Hiatus Hernia	0/224 (0%)	0	1/486 (0.2%)	1
Ileus	0/224 (0%)	0	1/486 (0.2%)	1
Inguinal Hernia	0/224 (0%)	0	2/486 (0.4%)	2
Intestinal Perforation	1/224 (0.4%)	1	0/486 (0%)	0
Irritable Bowel Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Nausea	2/224 (0.9%)	2	1/486 (0.2%)	1
Oesophageal Fistula	0/224 (0%)	0	1/486 (0.2%)	1
Proctalgia	1/224 (0.4%)	1	0/486 (0%)	0
Small Intestinal Obstruction	0/224 (0%)	0	1/486 (0.2%)	1
Umbilical Hernia	1/224 (0.4%)	1	0/486 (0%)	0
Vomiting	3/224 (1.3%)	3	2/486 (0.4%)	2
General disorders
Accidental Death	0/224 (0%)	0	1/486 (0.2%)	1
Adverse Drug Reaction	0/224 (0%)	0	1/486 (0.2%)	1
Asthenia	1/224 (0.4%)	1	0/486 (0%)	0
Axillary Pain	0/224 (0%)	0	1/486 (0.2%)	1
Chest Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Chest Pain	0/224 (0%)	0	3/486 (0.6%)	3
Device Breakage	0/224 (0%)	0	1/486 (0.2%)	1
Drug Withdrawal Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Facial Pain	0/224 (0%)	0	1/486 (0.2%)	1
Gait Disturbance	1/224 (0.4%)	1	1/486 (0.2%)	1
Hernia	1/224 (0.4%)	1	0/486 (0%)	0
Local Swelling	1/224 (0.4%)	1	0/486 (0%)	0
Non-Cardiac Chest Pain	3/224 (1.3%)	3	0/486 (0%)	0
Oedema Peripheral	0/224 (0%)	0	1/486 (0.2%)	1
Pain	1/224 (0.4%)	1	0/486 (0%)	0
Pyrexia	1/224 (0.4%)	1	0/486 (0%)	0
Soft Tissue Inflammation	1/224 (0.4%)	1	0/486 (0%)	0
Spinal Pain	0/224 (0%)	0	1/486 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	3/224 (1.3%)	3	1/486 (0.2%)	1
Gallbladder Disorder	1/224 (0.4%)	1	2/486 (0.4%)	2
Hepatomegaly	1/224 (0.4%)	1	0/486 (0%)	0
Immune system disorders
Drug Hypersensitivity	0/224 (0%)	0	1/486 (0.2%)	1
Hypersensitivity	0/224 (0%)	0	1/486 (0.2%)	1
Immunodeficiency Common Variable	0/224 (0%)	0	1/486 (0.2%)	1
Sarcoidosis	1/224 (0.4%)	1	0/486 (0%)	0
Infections and infestations
Bacterial Sepsis	1/224 (0.4%)	2	0/486 (0%)	0
Extradural Abscess	1/224 (0.4%)	1	0/486 (0%)	0
Kidney Infection	1/224 (0.4%)	1	0/486 (0%)	0
Meningitis Herpes	0/224 (0%)	0	1/486 (0.2%)	1
Paraoesophageal Abscess	0/224 (0%)	0	1/486 (0.2%)	1
Pneumonia Primary Atypical	0/224 (0%)	0	1/486 (0.2%)	1
Postoperative Wound Infection	0/224 (0%)	0	2/486 (0.4%)	2
Pyelonephritis	1/224 (0.4%)	1	1/486 (0.2%)	1
Respiratory Tract Infection	0/224 (0%)	0	1/486 (0.2%)	1
Sepsis	2/224 (0.9%)	2	0/486 (0%)	0
Staphylococcal Sepsis	1/224 (0.4%)	1	0/486 (0%)	0
Urinary Tract Infection	1/224 (0.4%)	1	0/486 (0%)	0
Wound Infection	0/224 (0%)	0	1/486 (0.2%)	1
Injury, poisoning and procedural complications
Accident At Work	0/224 (0%)	0	1/486 (0.2%)	1
Bone Fragmentation	0/224 (0%)	0	1/486 (0.2%)	1
Concussion	0/224 (0%)	0	1/486 (0.2%)	1
Epidural Fibrosis	1/224 (0.4%)	1	0/486 (0%)	0
Eye Injury	0/224 (0%)	0	1/486 (0.2%)	1
Fall	4/224 (1.8%)	5	6/486 (1.2%)	6
Gastrointestinal Anastomotic Leak	0/224 (0%)	0	1/486 (0.2%)	1
Injury	0/224 (0%)	0	1/486 (0.2%)	1
Intervertebral Disc Injury	1/224 (0.4%)	1	0/486 (0%)	0
Joint Injury	1/224 (0.4%)	1	3/486 (0.6%)	3
Laceration	1/224 (0.4%)	1	0/486 (0%)	0
Ligament Rupture	0/224 (0%)	0	1/486 (0.2%)	1
Lumbar Vertebral Fracture	1/224 (0.4%)	1	0/486 (0%)	0
Meniscus Lesion	2/224 (0.9%)	2	4/486 (0.8%)	4
Multiple Drug Overdose Accidental	0/224 (0%)	0	1/486 (0.2%)	1
Nerve Injury	0/224 (0%)	0	1/486 (0.2%)	1
Post Laminectomy Syndrome	0/224 (0%)	0	2/486 (0.4%)	2
Post Procedural Haematoma	1/224 (0.4%)	1	1/486 (0.2%)	1
Post Procedural Haemorrhage	1/224 (0.4%)	1	0/486 (0%)	0
Post-Traumatic Neck Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Procedural Haemorrhage	1/224 (0.4%)	1	0/486 (0%)	0
Procedural Headache	0/224 (0%)	0	1/486 (0.2%)	1
Pseudomeningocele	0/224 (0%)	0	1/486 (0.2%)	1
Pubis Fracture	0/224 (0%)	0	1/486 (0.2%)	1
Road Traffic Accident	6/224 (2.7%)	6	5/486 (1%)	5
Spinal Compression Fracture	0/224 (0%)	0	3/486 (0.6%)	3
Tendon Rupture	0/224 (0%)	0	1/486 (0.2%)	1
Tracheal Deviation	1/224 (0.4%)	1	0/486 (0%)	0
Investigations
Hepatic Enzyme Increased	0/224 (0%)	0	1/486 (0.2%)	1
Pancreatic Enzymes Increased	0/224 (0%)	0	1/486 (0.2%)	1
White Blood Cell Count Increased	1/224 (0.4%)	1	0/486 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/224 (0.4%)	1	0/486 (0%)	0
Hypokalaemia	1/224 (0.4%)	1	0/486 (0%)	0
Hyponatraemia	1/224 (0.4%)	1	0/486 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/224 (0.4%)	1	2/486 (0.4%)	4
Arthropathy	0/224 (0%)	0	3/486 (0.6%)	3
Back Pain	6/224 (2.7%)	6	8/486 (1.6%)	8
Bursitis	1/224 (0.4%)	1	1/486 (0.2%)	1
Cervical Spinal Stenosis	2/224 (0.9%)	2	15/486 (3.1%)	15
Chondromalacia	1/224 (0.4%)	1	0/486 (0%)	0
Compartment Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Exostosis	2/224 (0.9%)	2	12/486 (2.5%)	16
Facet Joint Syndrome	2/224 (0.9%)	2	1/486 (0.2%)	1
Fibromyalgia	0/224 (0%)	0	1/486 (0.2%)	1
Flank Pain	1/224 (0.4%)	1	0/486 (0%)	0
Intervertebral Disc Degeneration	9/224 (4%)	9	18/486 (3.7%)	18
Intervertebral Disc Disorder	4/224 (1.8%)	4	4/486 (0.8%)	4
Intervertebral Disc Protrusion	15/224 (6.7%)	15	32/486 (6.6%)	35
Intervertebral Disc Space Narrowing	1/224 (0.4%)	1	0/486 (0%)	0
Joint Crepitation	0/224 (0%)	0	1/486 (0.2%)	1
Joint Range Of Motion Decreased	1/224 (0.4%)	1	1/486 (0.2%)	1
Kyphosis	1/224 (0.4%)	1	0/486 (0%)	0
Ligament Disorder	0/224 (0%)	0	1/486 (0.2%)	1
Limb Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Lumbar Spinal Stenosis	4/224 (1.8%)	4	10/486 (2.1%)	10
Monarthritis	1/224 (0.4%)	1	0/486 (0%)	0
Muscle Spasms	1/224 (0.4%)	1	4/486 (0.8%)	4
Muscle Tightness	1/224 (0.4%)	1	0/486 (0%)	0
Muscle Twitching	0/224 (0%)	0	2/486 (0.4%)	2
Muscular Weakness	1/224 (0.4%)	1	1/486 (0.2%)	1
Musculoskeletal Chest Pain	0/224 (0%)	0	1/486 (0.2%)	1
Musculoskeletal Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Musculoskeletal Pain	3/224 (1.3%)	3	11/486 (2.3%)	13
Myalgia	0/224 (0%)	0	2/486 (0.4%)	2
Neck Pain	6/224 (2.7%)	7	16/486 (3.3%)	18
Osteoarthritis	3/224 (1.3%)	5	2/486 (0.4%)	2
Pain In Extremity	2/224 (0.9%)	2	9/486 (1.9%)	9
Pseudarthrosis	2/224 (0.9%)	2	16/486 (3.3%)	16
Rheumatoid Arthritis	1/224 (0.4%)	1	0/486 (0%)	0
Rotator Cuff Syndrome	5/224 (2.2%)	6	11/486 (2.3%)	12
Scoliosis	1/224 (0.4%)	1	0/486 (0%)	0
Spinal Column Stenosis	0/224 (0%)	0	2/486 (0.4%)	2
Spinal Osteoarthritis	5/224 (2.2%)	5	8/486 (1.6%)	8
Spondylolisthesis	4/224 (1.8%)	4	1/486 (0.2%)	1
Synovial Cyst	1/224 (0.4%)	1	1/486 (0.2%)	2
Tendon Disorder	1/224 (0.4%)	1	2/486 (0.4%)	2
Trigger Finger	1/224 (0.4%)	1	0/486 (0%)	0
Vertebral Foraminal Stenosis	5/224 (2.2%)	5	4/486 (0.8%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain Neoplasm	0/224 (0%)	0	1/486 (0.2%)	1
Fibrous Histiocytoma	0/224 (0%)	0	1/486 (0.2%)	1
Myolipoma	1/224 (0.4%)	1	0/486 (0%)	0
Prostate Cancer	0/224 (0%)	0	1/486 (0.2%)	1
Skin Cancer	0/224 (0%)	0	1/486 (0.2%)	1
Thyroid Adenoma	1/224 (0.4%)	1	0/486 (0%)	0
Nervous system disorders
Amnesia	0/224 (0%)	0	1/486 (0.2%)	1
Arachnoid Cyst	0/224 (0%)	0	1/486 (0.2%)	1
Burning Sensation	1/224 (0.4%)	1	0/486 (0%)	0
Carpal Tunnel Syndrome	2/224 (0.9%)	2	10/486 (2.1%)	10
Cerebrovascular Accident	1/224 (0.4%)	1	0/486 (0%)	0
Cervical Cord Compression	0/224 (0%)	0	1/486 (0.2%)	1
Cervicobrachial Syndrome	0/224 (0%)	0	7/486 (1.4%)	7
Convulsion	0/224 (0%)	0	2/486 (0.4%)	2
Dizziness	0/224 (0%)	0	1/486 (0.2%)	2
Dysaesthesia	2/224 (0.9%)	2	0/486 (0%)	0
Dyskinesia	0/224 (0%)	0	2/486 (0.4%)	2
Headache	3/224 (1.3%)	3	5/486 (1%)	5
Hypoaesthesia	1/224 (0.4%)	1	8/486 (1.6%)	9
Hypokinesia	0/224 (0%)	0	1/486 (0.2%)	1
Hypoxic-Ischaemic Encephalopathy	0/224 (0%)	0	1/486 (0.2%)	1
Loss Of Consciousness	3/224 (1.3%)	3	1/486 (0.2%)	1
Lumbar Radiculopathy	1/224 (0.4%)	1	2/486 (0.4%)	2
Migraine	1/224 (0.4%)	1	1/486 (0.2%)	1
Myelitis Transverse	0/224 (0%)	0	1/486 (0.2%)	1
Myelopathy	1/224 (0.4%)	1	1/486 (0.2%)	1
Nerve Root Compression	2/224 (0.9%)	2	2/486 (0.4%)	2
Paraesthesia	2/224 (0.9%)	2	4/486 (0.8%)	4
Perineurial Cyst	1/224 (0.4%)	1	1/486 (0.2%)	1
Radicular Pain	0/224 (0%)	0	7/486 (1.4%)	7
Radiculopathy	0/224 (0%)	0	1/486 (0.2%)	1
Sciatica	1/224 (0.4%)	1	0/486 (0%)	0
Sensory Loss	0/224 (0%)	0	1/486 (0.2%)	1
Spinal Cord Compression	1/224 (0.4%)	1	3/486 (0.6%)	3
Spinal Cord Ischaemia	0/224 (0%)	0	1/486 (0.2%)	1
Spinal Cord Oedema	0/224 (0%)	0	1/486 (0.2%)	1
Syncope	1/224 (0.4%)	1	1/486 (0.2%)	1
Thoracic Outlet Syndrome	0/224 (0%)	0	2/486 (0.4%)	2
Tremor	0/224 (0%)	0	1/486 (0.2%)	2
Ulnar Nerve Palsy	0/224 (0%)	0	1/486 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Foetal Hypokinesia	0/224 (0%)	0	1/486 (0.2%)	1
Premature Labour	0/224 (0%)	0	1/486 (0.2%)	1
Psychiatric disorders
Abnormal Behaviour	0/224 (0%)	0	1/486 (0.2%)	1
Alcohol Abuse	1/224 (0.4%)	1	0/486 (0%)	0
Anxiety	1/224 (0.4%)	1	1/486 (0.2%)	1
Depression	1/224 (0.4%)	1	3/486 (0.6%)	3
Schizophrenia	1/224 (0.4%)	1	0/486 (0%)	0
Stress	1/224 (0.4%)	1	0/486 (0%)	0
Suicidal Behaviour	0/224 (0%)	0	1/486 (0.2%)	1
Renal and urinary disorders
Calculus Ureteric	0/224 (0%)	0	2/486 (0.4%)	2
Cystitis Interstitial	1/224 (0.4%)	1	0/486 (0%)	0
Hydronephrosis	1/224 (0.4%)	1	0/486 (0%)	0
Nephrolithiasis	1/224 (0.4%)	1	2/486 (0.4%)	2
Neurogenic Bladder	1/224 (0.4%)	1	0/486 (0%)	0
Urinary Incontinence	0/224 (0%)	0	1/486 (0.2%)	1
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	1/224 (0.4%)	1	0/486 (0%)	0
Endometriosis	0/224 (0%)	0	1/486 (0.2%)	1
Menorrhagia	1/224 (0.4%)	1	0/486 (0%)	0
Prostatitis	1/224 (0.4%)	1	0/486 (0%)	0
Prostatomegaly	1/224 (0.4%)	1	0/486 (0%)	0
Scrotal Pain	1/224 (0.4%)	1	0/486 (0%)	0
Testicular Torsion	1/224 (0.4%)	1	0/486 (0%)	0
Foreign Body Aspiration	1/224 (0.4%)	1	0/486 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/224 (0.9%)	2	2/486 (0.4%)	2
Haemoptysis	0/224 (0%)	0	1/486 (0.2%)	1
Pharyngeal Haematoma	1/224 (0.4%)	1	0/486 (0%)	0
Pleural Effusion	0/224 (0%)	0	1/486 (0.2%)	1
Pneumothorax	0/224 (0%)	0	1/486 (0.2%)	1
Pulmonary Embolism	0/224 (0%)	0	1/486 (0.2%)	1
Pulmonary Sarcoidosis	1/224 (0.4%)	1	0/486 (0%)	0
Sleep Apnoea Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Throat Irritation	0/224 (0%)	0	1/486 (0.2%)	1
Vocal Cord Polyp	0/224 (0%)	0	1/486 (0.2%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/224 (0.4%)	1	0/486 (0%)	0
Keloid Scar	0/224 (0%)	0	1/486 (0.2%)	1
Surgical and medical procedures
Face Lift	0/224 (0%)	0	1/486 (0.2%)	1
Gastric Bypass	0/224 (0%)	0	1/486 (0.2%)	1
Tonsillectomy	0/224 (0%)	0	1/486 (0.2%)	1
Venous Operation	0/224 (0%)	0	1/486 (0.2%)	1
Vascular disorders
Aortic Aneurysm	0/224 (0%)	0	1/486 (0.2%)	1
Aortic Stenosis	0/224 (0%)	0	1/486 (0.2%)	1
Deep Vein Thrombosis	1/224 (0.4%)	1	0/486 (0%)	0
Haematoma	0/224 (0%)	0	2/486 (0.4%)	2
Hypertension	1/224 (0.4%)	1	0/486 (0%)	0
Hypotension	1/224 (0.4%)	1	0/486 (0%)	0
Orthostatic Hypertension	0/224 (0%)	0	1/486 (0.2%)	1
Peripheral Artery Aneurysm	1/224 (0.4%)	1	0/486 (0%)	0
Thrombophlebitis Superficial	1/224 (0.4%)	1	0/486 (0%)	0
Other (Not Including Serious) Adverse Events
	INFUSE® Bone Graft		Historical Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	186/224 (83%)		371/486 (76.3%)
Blood and lymphatic system disorders
Anaemia	1/224 (0.4%)	2	0/486 (0%)	0
Leukocytosis	4/224 (1.8%)	4	1/486 (0.2%)	1
Lymph Node Pain	0/224 (0%)	0	2/486 (0.4%)	2
Lymphadenopathy	0/224 (0%)	0	3/486 (0.6%)	3
Splenomegaly	1/224 (0.4%)	1	0/486 (0%)	0
Cardiac disorders
Arrhythmia	1/224 (0.4%)	1	0/486 (0%)	0
Atrial Fibrillation	1/224 (0.4%)	1	1/486 (0.2%)	1
Bradycardia	1/224 (0.4%)	1	0/486 (0%)	0
Coronary Artery Disease	1/224 (0.4%)	1	0/486 (0%)	0
Mitral Valve Incompetence	0/224 (0%)	0	2/486 (0.4%)	2
Palpitations	0/224 (0%)	0	5/486 (1%)	5
Sinus Bradycardia	1/224 (0.4%)	1	0/486 (0%)	0
Sinus Tachycardia	1/224 (0.4%)	1	0/486 (0%)	0
Supraventricular Extrasystoles	1/224 (0.4%)	1	0/486 (0%)	0
Ventricular Extrasystoles	2/224 (0.9%)	2	0/486 (0%)	0
Ear and labyrinth disorders
Deafness	0/224 (0%)	0	1/486 (0.2%)	1
Ear Pain	4/224 (1.8%)	4	0/486 (0%)	0
Hearing Impaired	1/224 (0.4%)	1	0/486 (0%)	0
Hyperacusis	1/224 (0.4%)	1	0/486 (0%)	0
Tinnitus	2/224 (0.9%)	2	0/486 (0%)	0
Vertigo	2/224 (0.9%)	2	1/486 (0.2%)	1
Vestibular Disorder	0/224 (0%)	0	1/486 (0.2%)	1
Endocrine disorders
Autoimmune Thyroiditis	1/224 (0.4%)	1	0/486 (0%)	0
Goitre	0/224 (0%)	0	1/486 (0.2%)	1
Hyperthyroidism	0/224 (0%)	0	1/486 (0.2%)	1
Hypothyroidism	2/224 (0.9%)	2	2/486 (0.4%)	2
Eye disorders
Astigmatism	1/224 (0.4%)	1	0/486 (0%)	0
Cataract	1/224 (0.4%)	1	0/486 (0%)	0
Conjunctivitis	2/224 (0.9%)	2	0/486 (0%)	0
Diplopia	0/224 (0%)	0	1/486 (0.2%)	1
Eye Pain	0/224 (0%)	0	1/486 (0.2%)	1
Photophobia	1/224 (0.4%)	1	0/486 (0%)	0
Vision Blurred	3/224 (1.3%)	3	1/486 (0.2%)	1
Visual Impairment	1/224 (0.4%)	1	2/486 (0.4%)	2
Vitreous Floaters	1/224 (0.4%)	1	0/486 (0%)	0
Gastrointestinal disorders
Abdominal Adhesions	1/224 (0.4%)	1	0/486 (0%)	0
Abdominal Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Abdominal Pain	3/224 (1.3%)	3	3/486 (0.6%)	3
Abdominal Pain Lower	0/224 (0%)	0	1/486 (0.2%)	1
Abdominal Pain Upper	0/224 (0%)	0	1/486 (0.2%)	1
Breath Odour	1/224 (0.4%)	1	0/486 (0%)	0
Change Of Bowel Habit	0/224 (0%)	0	1/486 (0.2%)	1
Constipation	1/224 (0.4%)	1	2/486 (0.4%)	2
Crohn's Disease	0/224 (0%)	0	1/486 (0.2%)	1
Diarrhoea	5/224 (2.2%)	5	2/486 (0.4%)	2
Dyspepsia	0/224 (0%)	0	1/486 (0.2%)	1
Dysphagia	34/224 (15.2%)	37	34/486 (7%)	36
Epigastric Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Eructation	2/224 (0.9%)	2	0/486 (0%)	0
Faecal Incontinence	0/224 (0%)	0	1/486 (0.2%)	1
Gastritis	1/224 (0.4%)	1	0/486 (0%)	0
Gastroduodenitis	1/224 (0.4%)	1	0/486 (0%)	0
Gastrooesophageal Reflux Disease	4/224 (1.8%)	4	7/486 (1.4%)	7
Haematochezia	0/224 (0%)	0	1/486 (0.2%)	1
Haemorrhoidal Haemorrhage	1/224 (0.4%)	1	0/486 (0%)	0
Haemorrhoids	0/224 (0%)	0	1/486 (0.2%)	1
Hiatus Hernia	2/224 (0.9%)	2	0/486 (0%)	0
Intestinal Polyp	0/224 (0%)	0	1/486 (0.2%)	1
Irritable Bowel Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Malocclusion	0/224 (0%)	0	1/486 (0.2%)	1
Nausea	8/224 (3.6%)	8	8/486 (1.6%)	8
Odynophagia	1/224 (0.4%)	1	0/486 (0%)	0
Oesophageal Oedema	0/224 (0%)	0	1/486 (0.2%)	1
Paraesthesia Oral	0/224 (0%)	0	1/486 (0.2%)	1
Periodontal Disease	0/224 (0%)	0	1/486 (0.2%)	1
Polyp Colorectal	0/224 (0%)	0	1/486 (0.2%)	1
Rectal Haemorrhage	0/224 (0%)	0	1/486 (0.2%)	1
Tongue Discolouration	1/224 (0.4%)	1	0/486 (0%)	0
Toothache	0/224 (0%)	0	1/486 (0.2%)	1
Vomiting	4/224 (1.8%)	4	5/486 (1%)	5
General disorders
Adverse Drug Reaction	2/224 (0.9%)	2	2/486 (0.4%)	2
Asthenia	5/224 (2.2%)	6	0/486 (0%)	0
Axillary Pain	0/224 (0%)	0	2/486 (0.4%)	2
Chest Discomfort	0/224 (0%)	0	2/486 (0.4%)	2
Chest Pain	2/224 (0.9%)	2	10/486 (2.1%)	10
Chills	1/224 (0.4%)	1	0/486 (0%)	0
Crepitations	1/224 (0.4%)	1	1/486 (0.2%)	1
Device Breakage	0/224 (0%)	0	3/486 (0.6%)	3
Device Connection Issue	0/224 (0%)	0	2/486 (0.4%)	2
Device Dislocation	0/224 (0%)	0	1/486 (0.2%)	1
Drug Withdrawal Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Facial Pain	0/224 (0%)	0	1/486 (0.2%)	1
Fatigue	6/224 (2.7%)	6	1/486 (0.2%)	1
Feeling Cold	0/224 (0%)	0	1/486 (0.2%)	1
Gait Disturbance	1/224 (0.4%)	1	2/486 (0.4%)	2
Implant Site Paraesthesia	0/224 (0%)	0	1/486 (0.2%)	1
Infusion Site Extravasation	1/224 (0.4%)	1	0/486 (0%)	0
Irritability	1/224 (0.4%)	1	0/486 (0%)	0
Local Swelling	7/224 (3.1%)	7	4/486 (0.8%)	4
Malaise	0/224 (0%)	0	2/486 (0.4%)	2
Non-Cardiac Chest Pain	1/224 (0.4%)	1	0/486 (0%)	0
Oedema Peripheral	4/224 (1.8%)	5	2/486 (0.4%)	2
Pain	3/224 (1.3%)	3	3/486 (0.6%)	3
Pyrexia	2/224 (0.9%)	2	3/486 (0.6%)	3
Sensation Of Foreign Body	1/224 (0.4%)	1	1/486 (0.2%)	1
Sensation Of Pressure	1/224 (0.4%)	1	0/486 (0%)	0
Spinal Pain	0/224 (0%)	0	2/486 (0.4%)	2
Swelling	1/224 (0.4%)	1	0/486 (0%)	0
Hepatobiliary disorders
Hepatic Steatosis	0/224 (0%)	0	1/486 (0.2%)	1
Immune system disorders
Drug Hypersensitivity	0/224 (0%)	0	1/486 (0.2%)	1
Hypersensitivity	2/224 (0.9%)	2	0/486 (0%)	0
Latex Allergy	1/224 (0.4%)	1	0/486 (0%)	0
Seasonal Allergy	1/224 (0.4%)	1	0/486 (0%)	0
Infections and infestations
Adenoviral Conjunctivitis	0/224 (0%)	0	1/486 (0.2%)	1
Bacterial Infection	0/224 (0%)	0	1/486 (0.2%)	1
Breast Abscess	1/224 (0.4%)	1	0/486 (0%)	0
Bronchitis	4/224 (1.8%)	4	1/486 (0.2%)	1
Cellulitis	0/224 (0%)	0	1/486 (0.2%)	1
Diverticulitis	0/224 (0%)	0	1/486 (0.2%)	1
Ear Infection	1/224 (0.4%)	1	2/486 (0.4%)	2
Gastroenteritis	0/224 (0%)	0	1/486 (0.2%)	1
Gastroenteritis Viral	1/224 (0.4%)	1	1/486 (0.2%)	1
Gastrointestinal Bacterial Infection	0/224 (0%)	0	1/486 (0.2%)	1
Herpes Zoster	1/224 (0.4%)	1	1/486 (0.2%)	1
Hordeolum	0/224 (0%)	0	1/486 (0.2%)	1
Incision Site Infection	1/224 (0.4%)	1	2/486 (0.4%)	2
Influenza	1/224 (0.4%)	1	3/486 (0.6%)	4
Kidney Infection	1/224 (0.4%)	1	0/486 (0%)	0
Laryngitis	0/224 (0%)	0	1/486 (0.2%)	1
Nasopharyngitis	3/224 (1.3%)	3	1/486 (0.2%)	1
Otitis Media	0/224 (0%)	0	1/486 (0.2%)	1
Pertussis	1/224 (0.4%)	1	0/486 (0%)	0
Pharyngitis	0/224 (0%)	0	1/486 (0.2%)	1
Pneumonia	3/224 (1.3%)	3	1/486 (0.2%)	1
Pneumonia Primary Atypical	0/224 (0%)	0	1/486 (0.2%)	1
Post Procedural Infection	0/224 (0%)	0	1/486 (0.2%)	1
Reiter's Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Rhinitis	1/224 (0.4%)	1	0/486 (0%)	0
Sinusitis	6/224 (2.7%)	6	5/486 (1%)	5
Staphylococcal Infection	1/224 (0.4%)	1	1/486 (0.2%)	1
Stitch Abscess	0/224 (0%)	0	2/486 (0.4%)	2
Tonsillitis	1/224 (0.4%)	1	0/486 (0%)	0
Tracheitis	1/224 (0.4%)	1	0/486 (0%)	0
Tracheobronchitis	0/224 (0%)	0	1/486 (0.2%)	1
Upper Respiratory Tract Infection	2/224 (0.9%)	2	2/486 (0.4%)	2
Urinary Tract Infection	2/224 (0.9%)	2	1/486 (0.2%)	1
Vulvovaginal Mycotic Infection	1/224 (0.4%)	2	0/486 (0%)	0
Injury, poisoning and procedural complications
Alcohol Poisoning	0/224 (0%)	0	1/486 (0.2%)	1
Ankle Fracture	0/224 (0%)	0	1/486 (0.2%)	1
Arthropod Bite	1/224 (0.4%)	1	0/486 (0%)	0
Arthropod Sting	1/224 (0.4%)	1	0/486 (0%)	0
Contusion	0/224 (0%)	0	2/486 (0.4%)	2
Dural Tear	0/224 (0%)	0	2/486 (0.4%)	2
Electric Shock	1/224 (0.4%)	1	0/486 (0%)	0
Endotracheal Intubation Complication	0/224 (0%)	0	1/486 (0.2%)	1
Epicondylitis	1/224 (0.4%)	1	4/486 (0.8%)	4
Face Injury	0/224 (0%)	0	1/486 (0.2%)	1
Fall	10/224 (4.5%)	10	27/486 (5.6%)	28
Foreign Body	1/224 (0.4%)	2	0/486 (0%)	0
Graft Complication	0/224 (0%)	0	1/486 (0.2%)	1
Hand Fracture	0/224 (0%)	0	1/486 (0.2%)	1
Head Injury	0/224 (0%)	0	5/486 (1%)	6
Incision Site Complication	1/224 (0.4%)	1	0/486 (0%)	0
Incision Site Erythema	3/224 (1.3%)	3	0/486 (0%)	0
Incision Site Haematoma	0/224 (0%)	0	1/486 (0.2%)	1
Incision Site Oedema	8/224 (3.6%)	8	0/486 (0%)	0
Incision Site Pain	0/224 (0%)	0	2/486 (0.4%)	2
Incorrect Dose Administered	1/224 (0.4%)	1	0/486 (0%)	0
Injury	0/224 (0%)	0	2/486 (0.4%)	2
Intervertebral Disc Injury	1/224 (0.4%)	1	0/486 (0%)	0
Joint Dislocation	1/224 (0.4%)	1	1/486 (0.2%)	1
Joint Injury	2/224 (0.9%)	2	1/486 (0.2%)	1
Laceration	1/224 (0.4%)	1	1/486 (0.2%)	1
Ligament Sprain	1/224 (0.4%)	1	4/486 (0.8%)	4
Limb Crushing Injury	0/224 (0%)	0	1/486 (0.2%)	1
Limb Injury	0/224 (0%)	0	1/486 (0.2%)	1
Meniscus Lesion	1/224 (0.4%)	1	1/486 (0.2%)	1
Muscle Strain	5/224 (2.2%)	5	7/486 (1.4%)	7
Nail Avulsion	0/224 (0%)	0	1/486 (0.2%)	1
Neck Injury	0/224 (0%)	0	1/486 (0.2%)	1
Periorbital Haematoma	0/224 (0%)	0	1/486 (0.2%)	1
Post Laminectomy Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Post Procedural Constipation	2/224 (0.9%)	2	1/486 (0.2%)	1
Post Procedural Haematoma	1/224 (0.4%)	1	1/486 (0.2%)	1
Post-Traumatic Neck Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Procedural Dizziness	0/224 (0%)	0	1/486 (0.2%)	1
Procedural Haemorrhage	0/224 (0%)	0	1/486 (0.2%)	1
Procedural Headache	0/224 (0%)	0	1/486 (0.2%)	1
Procedural Hypertension	2/224 (0.9%)	2	0/486 (0%)	0
Procedural Nausea	0/224 (0%)	0	5/486 (1%)	5
Procedural Vomiting	0/224 (0%)	0	5/486 (1%)	5
Road Traffic Accident	7/224 (3.1%)	7	15/486 (3.1%)	15
Spondylopathy Traumatic	1/224 (0.4%)	1	0/486 (0%)	0
Sports Injury	0/224 (0%)	0	1/486 (0.2%)	1
Toxicity To Various Agents	0/224 (0%)	0	1/486 (0.2%)	1
Tracheal Deviation	1/224 (0.4%)	1	1/486 (0.2%)	1
Wound Contamination	0/224 (0%)	0	1/486 (0.2%)	1
Wound Dehiscence	0/224 (0%)	0	1/486 (0.2%)	1
Wound Secretion	1/224 (0.4%)	1	3/486 (0.6%)	3
Blood Triglycerides Increased	0/224 (0%)	0	1/486 (0.2%)	1
Investigations
Blood Cholesterol Increased	2/224 (0.9%)	2	0/486 (0%)	0
Blood Pressure Increased	1/224 (0.4%)	1	3/486 (0.6%)	3
Blood Sodium Decreased	1/224 (0.4%)	1	0/486 (0%)	0
C-Reactive Protein Increased	0/224 (0%)	0	1/486 (0.2%)	1
Colonoscopy	1/224 (0.4%)	1	0/486 (0%)	0
Electrocardiogram T Wave Abnormal	1/224 (0.4%)	1	0/486 (0%)	0
Haematocrit Decreased	1/224 (0.4%)	1	0/486 (0%)	0
Haemoglobin Decreased	1/224 (0.4%)	1	0/486 (0%)	0
Heart Rate Increased	1/224 (0.4%)	1	0/486 (0%)	0
Intraocular Pressure Test Abnormal	0/224 (0%)	0	1/486 (0.2%)	1
Oxygen Saturation Decreased	1/224 (0.4%)	1	0/486 (0%)	0
Red Blood Cell Sedimentation Rate Increased	0/224 (0%)	0	1/486 (0.2%)	1
Reflex Test Abnormal	0/224 (0%)	0	1/486 (0.2%)	1
Sleep Study Abnormal	1/224 (0.4%)	1	0/486 (0%)	0
Transaminases Increased	0/224 (0%)	0	1/486 (0.2%)	1
Urine Output Decreased	0/224 (0%)	0	1/486 (0.2%)	1
Weight Decreased	0/224 (0%)	0	1/486 (0.2%)	1
White Blood Cell Count Increased	1/224 (0.4%)	1	0/486 (0%)	0
Gout	1/224 (0.4%)	1	3/486 (0.6%)	3
Metabolism and nutrition disorders
Dehydration	2/224 (0.9%)	2	0/486 (0%)	0
Diabetes Mellitus	1/224 (0.4%)	1	2/486 (0.4%)	2
Hyperglycaemia	1/224 (0.4%)	1	0/486 (0%)	0
Hyperlipidaemia	0/224 (0%)	0	3/486 (0.6%)	3
Hypokalaemia	1/224 (0.4%)	1	0/486 (0%)	0
Type 2 Diabetes Mellitus	2/224 (0.9%)	2	5/486 (1%)	5
Musculoskeletal and connective tissue disorders
Ankylosing Spondylitis	0/224 (0%)	0	1/486 (0.2%)	1
Arthralgia	7/224 (3.1%)	7	14/486 (2.9%)	14
Arthritis	0/224 (0%)	0	2/486 (0.4%)	2
Arthropathy	1/224 (0.4%)	1	2/486 (0.4%)	2
Back Pain	29/224 (12.9%)	34	44/486 (9.1%)	47
Bone Cyst	1/224 (0.4%)	1	0/486 (0%)	0
Bone Deformity	1/224 (0.4%)	1	0/486 (0%)	0
Bone Pain	0/224 (0%)	0	1/486 (0.2%)	1
Bunion	1/224 (0.4%)	1	0/486 (0%)	0
Bursitis	5/224 (2.2%)	5	3/486 (0.6%)	3
Cervical Spinal Stenosis	2/224 (0.9%)	2	6/486 (1.2%)	6
Chondromalacia	0/224 (0%)	0	1/486 (0.2%)	1
Coccydynia	0/224 (0%)	0	1/486 (0.2%)	1
Exostosis	7/224 (3.1%)	7	12/486 (2.5%)	13
Facet Joint Syndrome	2/224 (0.9%)	2	0/486 (0%)	0
Fibromyalgia	1/224 (0.4%)	1	4/486 (0.8%)	4
Flank Pain	0/224 (0%)	0	1/486 (0.2%)	1
Intervertebral Disc Degeneration	12/224 (5.4%)	15	20/486 (4.1%)	21
Intervertebral Disc Disorder	4/224 (1.8%)	4	4/486 (0.8%)	4
Intervertebral Disc Protrusion	18/224 (8%)	21	26/486 (5.3%)	27
Intervertebral Disc Space Narrowing	3/224 (1.3%)	3	0/486 (0%)	0
Joint Crepitation	5/224 (2.2%)	5	3/486 (0.6%)	4
Joint Hyperextension	1/224 (0.4%)	1	1/486 (0.2%)	1
Joint Laxity	0/224 (0%)	0	1/486 (0.2%)	1
Joint Lock	0/224 (0%)	0	2/486 (0.4%)	2
Joint Range Of Motion Decreased	0/224 (0%)	0	4/486 (0.8%)	4
Joint Stiffness	1/224 (0.4%)	1	2/486 (0.4%)	2
Joint Swelling	2/224 (0.9%)	2	3/486 (0.6%)	3
Kyphosis	2/224 (0.9%)	2	1/486 (0.2%)	1
Limb Discomfort	2/224 (0.9%)	2	2/486 (0.4%)	2
Lumbar Spinal Stenosis	1/224 (0.4%)	1	3/486 (0.6%)	3
Meniscal Degeneration	0/224 (0%)	0	1/486 (0.2%)	1
Muscle Atrophy	0/224 (0%)	0	2/486 (0.4%)	2
Muscle Fatigue	1/224 (0.4%)	1	2/486 (0.4%)	2
Muscle Spasms	21/224 (9.4%)	24	40/486 (8.2%)	46
Muscle Tightness	4/224 (1.8%)	5	11/486 (2.3%)	13
Muscle Twitching	1/224 (0.4%)	1	2/486 (0.4%)	2
Muscular Weakness	4/224 (1.8%)	4	10/486 (2.1%)	12
Musculoskeletal Chest Pain	1/224 (0.4%)	1	0/486 (0%)	0
Musculoskeletal Discomfort	11/224 (4.9%)	13	11/486 (2.3%)	12
Musculoskeletal Pain	37/224 (16.5%)	42	67/486 (13.8%)	77
Musculoskeletal Stiffness	9/224 (4%)	10	21/486 (4.3%)	24
Myalgia	3/224 (1.3%)	3	24/486 (4.9%)	27
Myofascial Pain Syndrome	0/224 (0%)	0	5/486 (1%)	5
Myofascial Spasm	2/224 (0.9%)	2	1/486 (0.2%)	1
Neck Mass	2/224 (0.9%)	2	0/486 (0%)	0
Neck Pain	63/224 (28.1%)	68	106/486 (21.8%)	122
Osteoarthritis	3/224 (1.3%)	3	5/486 (1%)	6
Osteochondritis	0/224 (0%)	0	1/486 (0.2%)	1
Osteopenia	1/224 (0.4%)	1	0/486 (0%)	0
Osteoporosis	0/224 (0%)	0	1/486 (0.2%)	1
Pain In Extremity	33/224 (14.7%)	37	64/486 (13.2%)	72
Pain In Jaw	1/224 (0.4%)	1	3/486 (0.6%)	3
Patellofemoral Pain Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Periarthritis	0/224 (0%)	0	1/486 (0.2%)	1
Plantar Fasciitis	0/224 (0%)	0	1/486 (0.2%)	1
Pseudarthrosis	0/224 (0%)	0	29/486 (6%)	29
Rheumatoid Arthritis	0/224 (0%)	0	2/486 (0.4%)	2
Rotator Cuff Syndrome	7/224 (3.1%)	7	10/486 (2.1%)	10
Sacroiliitis	0/224 (0%)	0	1/486 (0.2%)	1
Sensation Of Heaviness	0/224 (0%)	0	1/486 (0.2%)	1
Soft Tissue Disorder	1/224 (0.4%)	1	0/486 (0%)	0
Spinal Osteoarthritis	10/224 (4.5%)	12	11/486 (2.3%)	16
Spondylitis	0/224 (0%)	0	1/486 (0.2%)	1
Spondylolisthesis	3/224 (1.3%)	3	2/486 (0.4%)	2
Synovial Cyst	1/224 (0.4%)	1	1/486 (0.2%)	1
Temporomandibular Joint Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Tendonitis	1/224 (0.4%)	1	4/486 (0.8%)	4
Tenosynovitis	4/224 (1.8%)	4	1/486 (0.2%)	1
Trigger Finger	1/224 (0.4%)	1	0/486 (0%)	0
Vertebral Foraminal Stenosis	9/224 (4%)	9	2/486 (0.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	2/224 (0.9%)	2	0/486 (0%)	0
Colon Adenoma	1/224 (0.4%)	1	0/486 (0%)	0
Fibrous Cortical Defect	1/224 (0.4%)	1	0/486 (0%)	0
Haemangioma	1/224 (0.4%)	1	0/486 (0%)	0
Lipoma	1/224 (0.4%)	1	0/486 (0%)	0
Lung Neoplasm	0/224 (0%)	0	1/486 (0.2%)	1
Melanocytic Naevus	1/224 (0.4%)	1	0/486 (0%)	0
Nervous System Neoplasm	1/224 (0.4%)	1	0/486 (0%)	0
Skin Papilloma	0/224 (0%)	0	1/486 (0.2%)	1
Spinal Haemangioma	1/224 (0.4%)	1	1/486 (0.2%)	1
Thyroid Neoplasm	1/224 (0.4%)	1	0/486 (0%)	0
Nervous system disorders
Allodynia	1/224 (0.4%)	1	0/486 (0%)	0
Amnesia	1/224 (0.4%)	1	1/486 (0.2%)	1
Arachnoid Cyst	0/224 (0%)	0	1/486 (0.2%)	1
Balance Disorder	1/224 (0.4%)	1	1/486 (0.2%)	1
Burning Sensation	4/224 (1.8%)	4	7/486 (1.4%)	7
Carpal Tunnel Syndrome	10/224 (4.5%)	10	16/486 (3.3%)	16
Cerebral Ischaemia	0/224 (0%)	0	1/486 (0.2%)	1
Cervical Myelopathy	0/224 (0%)	0	1/486 (0.2%)	1
Cervicobrachial Syndrome	0/224 (0%)	0	5/486 (1%)	5
Cervicogenic Headache	1/224 (0.4%)	1	0/486 (0%)	0
Coordination Abnormal	0/224 (0%)	0	1/486 (0.2%)	1
Cubital Tunnel Syndrome	1/224 (0.4%)	1	1/486 (0.2%)	1
Dizziness	7/224 (3.1%)	7	7/486 (1.4%)	8
Dizziness Postural	0/224 (0%)	0	1/486 (0.2%)	1
Dysaesthesia	4/224 (1.8%)	4	3/486 (0.6%)	3
Dyskinesia	0/224 (0%)	0	1/486 (0.2%)	1
Grand Mal Convulsion	1/224 (0.4%)	1	0/486 (0%)	0
Headache	25/224 (11.2%)	26	39/486 (8%)	41
Horner's Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Hyperaesthesia	1/224 (0.4%)	1	1/486 (0.2%)	1
Hyperpathia	0/224 (0%)	0	1/486 (0.2%)	1
Hyperreflexia	0/224 (0%)	0	2/486 (0.4%)	2
Hypersomnia	2/224 (0.9%)	2	0/486 (0%)	0
Hypoaesthesia	34/224 (15.2%)	42	71/486 (14.6%)	97
Intracranial Hypotension	0/224 (0%)	0	1/486 (0.2%)	1
Loss Of Consciousness	0/224 (0%)	0	3/486 (0.6%)	3
Lumbar Radiculopathy	1/224 (0.4%)	1	0/486 (0%)	0
Memory Impairment	0/224 (0%)	0	2/486 (0.4%)	2
Migraine	5/224 (2.2%)	5	6/486 (1.2%)	6
Muscle Contractions Involuntary	0/224 (0%)	0	1/486 (0.2%)	1
Myelopathy	0/224 (0%)	0	3/486 (0.6%)	3
Narcolepsy	0/224 (0%)	0	1/486 (0.2%)	1
Nerve Compression	0/224 (0%)	0	2/486 (0.4%)	2
Nerve Root Compression	0/224 (0%)	0	2/486 (0.4%)	2
Nervous System Disorder	0/224 (0%)	0	1/486 (0.2%)	1
Neuralgia	1/224 (0.4%)	1	0/486 (0%)	0
Neuritis	2/224 (0.9%)	2	0/486 (0%)	0
Neuropathy Peripheral	0/224 (0%)	0	1/486 (0.2%)	1
Paraesthesia	21/224 (9.4%)	25	45/486 (9.3%)	51
Peripheral Motor Neuropathy	0/224 (0%)	0	1/486 (0.2%)	1
Piriformis Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Polyneuropathy	0/224 (0%)	0	1/486 (0.2%)	1
Poor Quality Sleep	1/224 (0.4%)	1	0/486 (0%)	0
Post-Traumatic Headache	0/224 (0%)	0	2/486 (0.4%)	2
Presyncope	0/224 (0%)	0	1/486 (0.2%)	1
Radicular Pain	1/224 (0.4%)	1	21/486 (4.3%)	21
Radicular Syndrome	1/224 (0.4%)	1	0/486 (0%)	0
Radiculopathy	1/224 (0.4%)	1	0/486 (0%)	0
Restless Legs Syndrome	1/224 (0.4%)	1	1/486 (0.2%)	1
Sciatica	2/224 (0.9%)	2	2/486 (0.4%)	2
Sensory Disturbance	0/224 (0%)	0	2/486 (0.4%)	2
Sensory Loss	1/224 (0.4%)	1	5/486 (1%)	5
Sinus Headache	1/224 (0.4%)	1	1/486 (0.2%)	1
Spinal Cord Compression	0/224 (0%)	0	1/486 (0.2%)	1
Spinal Cord Disorder	0/224 (0%)	0	1/486 (0.2%)	1
Syncope	1/224 (0.4%)	1	3/486 (0.6%)	3
Tension Headache	1/224 (0.4%)	1	1/486 (0.2%)	1
Thoracic Outlet Syndrome	0/224 (0%)	0	2/486 (0.4%)	2
Tremor	1/224 (0.4%)	1	2/486 (0.4%)	2
Ulnar Neuritis	0/224 (0%)	0	3/486 (0.6%)	3
Viith Nerve Paralysis	1/224 (0.4%)	1	0/486 (0%)	0
Vocal Cord Paralysis	1/224 (0.4%)	1	3/486 (0.6%)	3
Pregnancy, puerperium and perinatal conditions
Gestational Diabetes	0/224 (0%)	0	1/486 (0.2%)	1
Psychiatric disorders
Affect Lability	1/224 (0.4%)	1	0/486 (0%)	0
Anxiety	4/224 (1.8%)	4	7/486 (1.4%)	8
Bipolar I Disorder	1/224 (0.4%)	1	0/486 (0%)	0
Confusional State	1/224 (0.4%)	1	1/486 (0.2%)	1
Delirium	1/224 (0.4%)	1	0/486 (0%)	0
Depression	10/224 (4.5%)	10	10/486 (2.1%)	10
Disorientation	1/224 (0.4%)	1	0/486 (0%)	0
Insomnia	8/224 (3.6%)	8	7/486 (1.4%)	7
Libido Decreased	2/224 (0.9%)	2	0/486 (0%)	0
Mood Swings	0/224 (0%)	0	1/486 (0.2%)	1
Panic Attack	1/224 (0.4%)	1	1/486 (0.2%)	1
Sleep Disorder	3/224 (1.3%)	3	2/486 (0.4%)	2
Stress	3/224 (1.3%)	3	1/486 (0.2%)	1
Renal and urinary disorders
Dysuria	1/224 (0.4%)	1	0/486 (0%)	0
Enuresis	1/224 (0.4%)	1	0/486 (0%)	0
Hydronephrosis	1/224 (0.4%)	1	0/486 (0%)	0
Hydroureter	1/224 (0.4%)	1	0/486 (0%)	0
Incontinence	0/224 (0%)	0	1/486 (0.2%)	1
Nephrolithiasis	4/224 (1.8%)	4	2/486 (0.4%)	2
Urinary Incontinence	0/224 (0%)	0	4/486 (0.8%)	4
Urinary Retention	1/224 (0.4%)	1	0/486 (0%)	0
Reproductive system and breast disorders
Breast Mass	1/224 (0.4%)	1	0/486 (0%)	0
Erectile Dysfunction	1/224 (0.4%)	1	1/486 (0.2%)	1
Menopausal Symptoms	1/224 (0.4%)	1	0/486 (0%)	0
Uterine Polyp	0/224 (0%)	0	1/486 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/224 (0%)	0	1/486 (0.2%)	1
Asthma	0/224 (0%)	0	2/486 (0.4%)	2
Atelectasis	2/224 (0.9%)	2	0/486 (0%)	0
Bronchial Hyperreactivity	1/224 (0.4%)	1	0/486 (0%)	0
Bronchospasm	1/224 (0.4%)	1	0/486 (0%)	0
Choking	0/224 (0%)	0	1/486 (0.2%)	1
Cough	4/224 (1.8%)	4	2/486 (0.4%)	2
Dysphonia	3/224 (1.3%)	4	6/486 (1.2%)	6
Dyspnoea	5/224 (2.2%)	5	2/486 (0.4%)	2
Hiccups	0/224 (0%)	0	1/486 (0.2%)	1
Hyperventilation	0/224 (0%)	0	1/486 (0.2%)	1
Increased Upper Airway Secretion	0/224 (0%)	0	1/486 (0.2%)	1
Laryngeal Erythema	0/224 (0%)	0	1/486 (0.2%)	1
Laryngeal Oedema	1/224 (0.4%)	1	0/486 (0%)	0
Nasal Cyst	0/224 (0%)	0	1/486 (0.2%)	1
Nasal Inflammation	1/224 (0.4%)	1	0/486 (0%)	0
Oropharyngeal Discomfort	0/224 (0%)	0	1/486 (0.2%)	1
Oropharyngeal Pain	7/224 (3.1%)	7	2/486 (0.4%)	2
Painful Respiration	0/224 (0%)	0	1/486 (0.2%)	1
Pharyngeal Disorder	1/224 (0.4%)	1	0/486 (0%)	0
Pharyngeal Oedema	1/224 (0.4%)	1	3/486 (0.6%)	3
Pulmonary Congestion	0/224 (0%)	0	1/486 (0.2%)	1
Pulmonary Fibrosis	0/224 (0%)	0	1/486 (0.2%)	1
Rales	1/224 (0.4%)	1	0/486 (0%)	0
Respiratory Failure	0/224 (0%)	0	1/486 (0.2%)	1
Respiratory Tract Congestion	2/224 (0.9%)	3	0/486 (0%)	0
Rhinitis Allergic	0/224 (0%)	0	1/486 (0.2%)	1
Rhinorrhoea	1/224 (0.4%)	1	0/486 (0%)	0
Sinus Disorder	1/224 (0.4%)	1	1/486 (0.2%)	1
Sleep Apnoea Syndrome	0/224 (0%)	0	3/486 (0.6%)	3
Sneezing	1/224 (0.4%)	1	0/486 (0%)	0
Snoring	3/224 (1.3%)	3	0/486 (0%)	0
Throat Irritation	1/224 (0.4%)	1	0/486 (0%)	0
Throat Tightness	0/224 (0%)	0	2/486 (0.4%)	2
Upper-Airway Cough Syndrome	0/224 (0%)	0	1/486 (0.2%)	1
Vocal Cord Thickening	1/224 (0.4%)	1	0/486 (0%)	0
Wheezing	2/224 (0.9%)	2	1/486 (0.2%)	1
Skin and subcutaneous tissue disorders
Acne	0/224 (0%)	0	1/486 (0.2%)	1
Dermal Cyst	2/224 (0.9%)	2	0/486 (0%)	0
Dermatitis Acneiform	1/224 (0.4%)	1	0/486 (0%)	0
Dermatitis Allergic	1/224 (0.4%)	1	0/486 (0%)	0
Dermatitis Contact	2/224 (0.9%)	2	3/486 (0.6%)	3
Dermatitis Exfoliative	0/224 (0%)	0	1/486 (0.2%)	1
Drug Eruption	0/224 (0%)	0	3/486 (0.6%)	3
Erythema	2/224 (0.9%)	2	0/486 (0%)	0
Hyperkeratosis	1/224 (0.4%)	1	0/486 (0%)	0
Leukoplakia	1/224 (0.4%)	1	0/486 (0%)	0
Night Sweats	1/224 (0.4%)	1	0/486 (0%)	0
Pruritus	2/224 (0.9%)	2	0/486 (0%)	0
Rash	2/224 (0.9%)	2	1/486 (0.2%)	1
Rash Macular	0/224 (0%)	0	1/486 (0.2%)	1
Rash Pruritic	1/224 (0.4%)	1	0/486 (0%)	0
Rosacea	1/224 (0.4%)	1	0/486 (0%)	0
Scar	0/224 (0%)	0	2/486 (0.4%)	2
Skin Burning Sensation	0/224 (0%)	0	1/486 (0.2%)	1
Skin Discolouration	0/224 (0%)	0	1/486 (0.2%)	1
Skin Irritation	0/224 (0%)	0	1/486 (0.2%)	1
Urticaria	0/224 (0%)	0	1/486 (0.2%)	1
Social circumstances
Physical Assault	0/224 (0%)	0	1/486 (0.2%)	1
Surgical and medical procedures
Arthrodesis	0/224 (0%)	0	1/486 (0.2%)	1
Suture Removal	0/224 (0%)	0	1/486 (0.2%)	1
Vascular disorders
Deep Vein Thrombosis	0/224 (0%)	0	1/486 (0.2%)	1
Flushing	1/224 (0.4%)	1	0/486 (0%)	0
Haematoma	0/224 (0%)	0	1/486 (0.2%)	1
Hypertension	5/224 (2.2%)	5	6/486 (1.2%)	6
Hypotension	1/224 (0.4%)	1	1/486 (0.2%)	1
Peripheral Coldness	0/224 (0%)	0	1/486 (0.2%)	1
Thrombophlebitis Superficial	2/224 (0.9%)	2	0/486 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.