LDR Spine USA Mobi-C(R) Cervical Disc Prosthesis IDE

• ClinicalTrials.gov Identifier: NCT00389597
• Recruitment Status: Completed
• First Posted: October 19, 2006
• Results First Posted: May 1, 2014
• Last Update Posted: December 11, 2017
• Sponsor: LDR Spine USA
• Information provided by (Responsible Party): LDR Spine USA

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Degenerative Disc Disease
• Intervention: Device: Cervical Artificial Disc
• Enrollment: 599

Participant Flow

Recruitment Details	One Level TDR Arm: 169 subjects randomized (5 not operated) One Level ACDF Arm: 87 subjects randomized (6 not operated) Two level TDR arm: 232 subjects randomized (7 not operated). Two Level ACDF Arm: 115 subjects randomized (10 not operated)
Pre-assignment Details	1 level TDR enrolled 184 incl15 training cases (2 withdrew consent, 1 AE, 2 other). 1 level ACDF enrolled 87 with no training cases (4 withdrew consent, 2 other) for 245 randomized subjects. 2 level TDR enrolled 241 incl. 9 training cases (1 withdrew consent, 6 other); 2 Level ACDF enrolled 115 with no training cases (4 withdrew consent, 6 other)

Arm/Group Title	1 Level TDR	1 Level ACDF	2 Level TDR	2 Level ACDF
Arm/Group Description	Cervical artificial disc (investigational device) at 1 level	1 level control procedure (ACDF)	Cervical artificial disc (investigational device) at 2 levels	2 level control procedure (ACDF)
Period Title: Overall Study
Started	164	81	225	105
24 mo	156	75	221	99
Completed	156	75	221	99
Not Completed	8	6	4	6
Reason Not Completed
Lost to Follow-up	8	6	4	6

Baseline Characteristics

Arm/Group Title		1 Level TDR	1 Level ACDF	2 Level TDR	2 Level ACDF	Total
Arm/Group Description		Cervical artificial disc (investigational device) at 1 level	1 level control procedure (ACDF)	Cervical artificial disc (investigational device) at 2 levels	2 level control procedure (ACDF)	Total of all reporting groups
Overall Number of Baseline Participants		164	81	225	105	575
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	81 participants	225 participants	105 participants	575 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	161 98.2%	80 98.8%	222 98.7%	101 96.2%	564 98.1%
	>=65 years	3 1.8%	1 1.2%	3 1.3%	4 3.8%	11 1.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	81 participants	225 participants	105 participants	575 participants
	Female	86 52.4%	45 55.6%	112 49.8%	45 42.9%	288 50.1%
	Male	78 47.6%	36 44.4%	113 50.2%	60 57.1%	287 49.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	164 participants	81 participants	225 participants	105 participants	575 participants
		164	81	225	105	575

Outcome Measures

1. Primary Outcome

Title	Composite Definition of Study Success
Description	An individual subject in either treatment group was considered a success if the following criteria were met at 24 months: Improvement in Neck Disability Index of at least 15/50 points in subjects with baseline Neck Disability Index scores of >= 30/50 points, or a 50% improvement in subjects with a baseline Neck Disability Score score of <30/50 where the Neck Disability Index is a measure designed to enable the physician to understand how much a subject's neck pain has affected his ability to manage everyday activities.; No study failures due to secondary surgical interventions at the index level; Absence of major complications defined as radiographic failure, neurologic failure, or failure by adverse event as adjudicated by the CEC
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

includes study failures, per protocol, that are carried forward for overall success

Arm/Group Title	1 Level ACDF	1 Level TDR	2 Level ACDF	2 Level TDR
Arm/Group Description:	control procedure (ACDF) at one level	Cervical artificial disc (investigational device) at 1 level	Cervical artificial disc (investigational device) at 2 levels compared with control procedure (ACDF) at two levels	control procedure (ACDF) at two levels
Overall Number of Participants Analyzed	75	156	99	221
Measure Type: Number; Unit of Measure: percentage of subjects analyzed
	65.3	73.7	37.4	69.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1 Level ACDF, 1 Level TDR
	Comments	1 Level: Ho: pm-pc <=-0.1 (inferiority) Alternative hypothesis: Ha: pm - pc > -0.1 Where pm = the proportion of success in the Mobi-C group and the Pc = the proportion of success in the ACDF group.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The 95% one-sided confidence bound for testing non-inferiority using two proportion test with 10% non-inferiority margin.
Statistical Test of Hypothesis	P-Value	0.0021
	Comments	[Not Specified]
	Method	Farrington Manning
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2 Level ACDF, 2 Level TDR
	Comments	2 Level: Ho: pm-pc <=-0.1 (inferiority) Alternative hypothesis: Ha: pm - pc > -0.1 Where pm = the proportion of success in the Mobi-C group and the Pc = the proportion of success in the ACDF group. 2 Level: Ho: pm-pc <= 0 (not superior) Alternative hypothesis: Ha: pm-pc >0 Where pm = the proportion of success in the Mobi-C group and the Pc = the proportion of success in the ACDF group.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The 95% one-sided confidence bound for testing non-inferiority using two proportioned test with a 10% non-inferiority margin.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Farrington-Manning
	Comments	[Not Specified]

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Adverse events are reported on all patients treated, including 24 surgical training subjects. Randomized total = 575, safety population total =599
Arm/Group Title	1 Level TDR Arm		1 Level ACDF Arm		2 Level TDR Arm		2 Level ACDF Arm
Arm/Group Description	Cervical artificial disc (investigational device) at 1 level		[Not Specified]		Cervical artificial disc (investigational device) at 2 levels		[Not Specified]
All-Cause Mortality
	1 Level TDR Arm		1 Level ACDF Arm		2 Level TDR Arm		2 Level ACDF Arm
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	1 Level TDR Arm		1 Level ACDF Arm		2 Level TDR Arm		2 Level ACDF Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/179 (17.88%)		21/81 (25.93%)		56/234 (23.93%)		34/105 (32.38%)
Cardiac disorders
Cardiovascular † 1	4/179 (2.23%)	4	1/81 (1.23%)	1	7/234 (2.99%)	9	1/105 (0.95%)	1
Gastrointestinal disorders
Gastrointestinal † 1	5/179 (2.79%)	8	1/81 (1.23%)	2	3/234 (1.28%)	3	2/105 (1.90%)	2
General disorders
Death † 1 [1]	0/179 (0.00%)	0	0/81 (0.00%)	0	1/234 (0.43%)	1	0/105 (0.00%)	0
Other † 1 [2]	6/179 (3.35%)	8	1/81 (1.23%)	1	12/234 (5.13%)	14	9/105 (8.57%)	13
Infections and infestations
Infection † 1 [3]	3/179 (1.68%)	5	4/81 (4.94%)	6	6/234 (2.56%)	9	3/105 (2.86%)	4
Musculoskeletal and connective tissue disorders
Heterotopic Ossification † 1 [4]	1/179 (0.56%)	1	0/81 (0.00%)	0	0/234 (0.00%)	0	0/105 (0.00%)	0
Neck and/or Arm Pain † 1 [5]	3/179 (1.68%)	4	2/81 (2.47%)	4	10/234 (4.27%)	15	6/105 (5.71%)	8
Non-union † 1 [6]	0/179 (0.00%)	0	5/81 (6.17%)	5	1/234 (0.43%)	3	11/105 (10.48%)	14
Other pain † 1 [7]	6/179 (3.35%)	7	4/81 (4.94%)	4	10/234 (4.27%)	15	3/105 (2.86%)	3
Spinal Disorder † 1 [8]	3/179 (1.68%)	3	7/81 (8.64%)	8	4/234 (1.71%)	4	7/105 (6.67%)	8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer † 1 [9]	1/179 (0.56%)	2	1/81 (1.23%)	1	1/234 (0.43%)	1	0/105 (0.00%)	0
Nervous system disorders
Neurological † 1 [10]	5/179 (2.79%)	8	3/81 (3.70%)	4	5/234 (2.14%)	5	5/105 (4.76%)	5
Upper Extremity Nerve Entrapment † 1 [11]	3/179 (1.68%)	3	1/81 (1.23%)	2	4/234 (1.71%)	5	0/105 (0.00%)	0
Renal and urinary disorders
Urogenital † 1	2/179 (1.12%)	3	0/81 (0.00%)	0	1/234 (0.43%)	1	1/105 (0.95%)	1
Respiratory, thoracic and mediastinal disorders
Dysphagia/Dysphonia † 1 [12]	0/179 (0.00%)	0	1/81 (1.23%)	2	2/234 (0.85%)	2	2/105 (1.90%)	2
Respiratory † 1	2/179 (1.12%)	2	1/81 (1.23%)	1	3/234 (1.28%)	3	0/105 (0.00%)	0
Skin and subcutaneous tissue disorders
Wound Issue - Non-infection † 1 [13]	0/179 (0.00%)	0	2/81 (2.47%)	2	2/234 (0.85%)	2	3/105 (2.86%)	3
Social circumstances
Trauma † 1 [14]	4/179 (2.23%)	5	5/81 (6.17%)	8	7/234 (2.99%)	10	2/105 (1.90%)
Surgical and medical procedures
Anatomy/Technical Difficulty † 1 [15]	1/179 (0.56%)	1	0/81 (0.00%)	0	1/234 (0.43%)	1	1/105 (0.95%)	1
Malpositioned implant † 1 [16]	1/179 (0.56%)	1	1/81 (1.23%)	1	1/234 (0.43%)	1	0/105 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0); [1] includes all deaths not related to the device - respiratory, cardiac, etc; [2] includes Blood/Lymphatic, Congenital/Genetic, Ear/Labyrinth, Endocrine, Eye, Immune, Metabolism/Nutrition, Musculoskeletal /CT, Benign Neoplasm, Nervous, Psychiatric, Repro, Skin, Vascular , Poisoning, Pregnancy, Social & surgical/Medical procedures; [3] Infection includes Superficial Wound - Cervical, Deep Wound - Cervical, Other Wound - Non Study Surgery, both Systemic and Local; [4] Heterotopic Ossification includes Cervical - Index Level, Cervical - Adjacent Level and Non Cervical; [5] Neck and/or Arm Pain includes pain (and related pain terms) specific to neck (cervical spine) and arm pain (and related pain terms) specific to arm (spinal disorders are recorded elsewhere).; [6] Non-Union includes non-union, cervical fusion failure, pseudoarthrosis, and pending non-unions as reported ; limited to study surgery related events of non-union.; [7] Other Pain including Shoulder, Back, Torso, Lower Extremity, Headache, Other; [8] Spinal Disorder including Cervical - Study Surgery, Cervical - Non Study Surgery and Non Cervical; [9] All reported of AEs of cancer (malignancy or malignant tumor/neoplasm); [10] Neurological including Upper Extremity - Sensory, motor, reflex; Lower Extremity - Sensory, motor, reflex; Upper & Lower Extremity - Sensory, motor, reflex; neck, back, spinal cord disturbance; gait disturbance, non specific and other; [11] including all reported AEs of Carpel Tunnel Syndrome and Cubital Tunnel Syndrome, including AEs directly attributed to Carpel Tunnel Syndrome or Cubital Tunnel Syndrome, as well as Carpal Tunnel surgery.; [12] includes all reported AEs of Dysphagia and other terms consistent with "difficulty swallowing" and all reported AEs of Dysphonia and other terms consistent with "voice change and/or disruption".; [13] including Hematoma, Hematoma Evacuation and CSF Leakage; [14] includes falls, motor vehicle accidents, assault, injury, etc. This category includes both cervical and non-cervical AEs of Trauma.; [15] Anatomy/Technical Difficulty includes Cervical - Study Surgery, Cervical - Non Study Surgery and Non Cervical; [16] includes misplaced screw, subsidence, a sub optimal or undesired position, regardless of causality. This is not mutually exclusive to surgeon error or sub-optimal placement of the original implant configuration.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	1 Level TDR Arm		1 Level ACDF Arm		2 Level TDR Arm		2 Level ACDF Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	170/179 (94.97%)		75/81 (92.59%)		209/234 (89.32%)		100/105 (95.24%)
Cardiac disorders
Cardiovascular † 1	20/179 (11.17%)	26	10/81 (12.35%)	10	21/234 (8.97%)	29	10/105 (9.52%)	12
Gastrointestinal disorders
Gastrointestinal † 1	39/179 (21.79%)	60	15/81 (18.52%)	37	47/234 (20.09%)	97	32/105 (30.48%)	52
General disorders
Death † 1	0/179 (0.00%)	0	0/81 (0.00%)	0	1/234 (0.43%)	1	0/105 (0.00%)	0
Other † 1	77/179 (43.02%)	114	33/81 (40.74%)	66	99/234 (42.31%)	189	58/105 (55.24%)	104
Infections and infestations
Infection † 1	33/179 (18.44%)	51	20/81 (24.69%)	28	56/234 (23.93%)	98	30/105 (28.57%)	50
Musculoskeletal and connective tissue disorders
Heterotopic Ossification † 1	9/179 (5.03%)	10	4/81 (4.94%)	4	6/234 (2.56%)	6	1/105 (0.95%)	1
Neck and/or Arm Pain † 1	101/179 (56.42%)	212	47/81 (58.02%)	98	102/234 (43.59%)	167	63/105 (60.00%)	111
Non-Union † 1	0/179 (0.00%)	0	4/81 (4.94%)	4	1/234 (0.43%)	3	13/105 (12.38%)	18
Other Pain † 1	102/179 (56.98%)	226	47/81 (58.02%)	144	131/234 (55.98%)	267	64/105 (60.95%)	132
Spinal Disorder † 1	6/179 (3.35%)	7	10/81 (12.35%)	12	13/234 (5.56%)	18	13/105 (12.38%)	20
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer † 1	4/179 (2.23%)	5	1/81 (1.23%)	2	3/234 (1.28%)	3	1/105 (0.95%)	1
Nervous system disorders
Neurological † 1	121/179 (67.60%)	401	52/81 (64.20%)	215	124/234 (52.99%)	426	78/105 (74.29%)	278
Upper Extremity Nerve Entrapment † 1	8/179 (4.47%)	9	4/81 (4.94%)	5	13/234 (5.56%)	16	6/105 (5.71%)	7
Renal and urinary disorders
Urogenital † 1	9/179 (5.03%)	11	9/81 (11.11%)	12	15/234 (6.41%)	23	10/105 (9.52%)	14
Respiratory, thoracic and mediastinal disorders
Dysphagia/Dysphonia † 1	20/179 (11.17%)	26	17/81 (20.99%)	20	39/234 (16.67%)	43	24/105 (22.86%)	27
Respiratory † 1	6/179 (3.35%)	6	6/81 (7.41%)	8	19/234 (8.12%)	29	11/105 (10.48%)	12
Skin and subcutaneous tissue disorders
Wound Issue -- Non-Infection † 1	1/179 (0.56%)	1	3/81 (3.70%)	3	4/234 (1.71%)	4	3/105 (2.86%)	3
Social circumstances
Trauma † 1	47/179 (26.26%)	70	20/81 (24.69%)	38	52/234 (22.22%)	89	20/105 (19.05%)	36
Surgical and medical procedures
Anatomy/Techical Difficulty † 1	11/179 (6.15%)	12	2/81 (2.47%)	4	9/234 (3.85%)	9	5/105 (4.76%)	5
Malpositioned Implant † 1	2/179 (1.12%)	2	1/81 (1.23%)	1	4/234 (1.71%)	4	0/105 (0.00%)	0
Vascular disorders
Vascular Intraoperative † 1	1/179 (0.56%)	1	0/81 (0.00%)	0	0/234 (0.00%)	0	1/105 (0.95%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The clinical site must submit to the Company, for review, any manuscripts, papers, summaries, abstracts, outlines or other media for publication at least 60 days before disclosure for the Company to review. The company has 30 days to review the proposed publication for any patentable subject matter or designated confidential information or confidential health information and by written notice to the site/PI identify such text so that the Company has time to file a patent application.

Results Point of Contact

• Name/Title: Noah Bartsch, VP, Clinical,Regulatory,Quality
• Organization: LDR Spine
• Phone: 512-344-3319
• EMail: noah.bartsch@ldrspine.com

Publications of Results:

Hisey MS, Bae HW, Davis R, Gaede S, Hoffman G, Kim K, Nunley PD, Peterson D, Rashbaum R, Stokes J. Multi-center, prospective, randomized, controlled investigational device exemption clinical trial comparing Mobi-C Cervical Artificial Disc to anterior discectomy and fusion in the treatment of symptomatic degenerative disc disease in the cervical spine. Int J Spine Surg. 2014 Dec 1;8. doi: 10.14444/1007. eCollection 2014.

Davis RJ, Kim KD, Hisey MS, Hoffman GA, Bae HW, Gaede SE, Rashbaum RF, Nunley PD, Peterson DL, Stokes JK. Cervical total disc replacement with the Mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled multicenter clinical trial: clinical article. J Neurosurg Spine. 2013 Nov;19(5):532-45. doi: 10.3171/2013.6.SPINE12527. Epub 2013 Sep 6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Radcliff K, Davis RJ, Hisey MS, Nunley PD, Hoffman GA, Jackson RJ, Bae HW, Albert T, Coric D. Long-term Evaluation of Cervical Disc Arthroplasty with the Mobi-C© Cervical Disc: A Randomized, Prospective, Multicenter Clinical Trial with Seven-Year Follow-up. Int J Spine Surg. 2017 Nov 28;11:31. doi: 10.14444/4031. eCollection 2017.

Radcliff K, Coric D, Albert T. Five-year clinical results of cervical total disc replacement compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled, multicenter investigational device exemption clinical trial. J Neurosurg Spine. 2016 Aug;25(2):213-24. doi: 10.3171/2015.12.SPINE15824. Epub 2016 Mar 25. Erratum in: J Neurosurg Spine. 2016 Aug;25(2):280.

Jackson RJ, Davis RJ, Hoffman GA, Bae HW, Hisey MS, Kim KD, Gaede SE, Nunley PD. Subsequent surgery rates after cervical total disc replacement using a Mobi-C Cervical Disc Prosthesis versus anterior cervical discectomy and fusion: a prospective randomized clinical trial with 5-year follow-up. J Neurosurg Spine. 2016 May;24(5):734-45. doi: 10.3171/2015.8.SPINE15219. Epub 2016 Jan 22.

Davis RJ, Nunley PD, Kim KD, Hisey MS, Jackson RJ, Bae HW, Hoffman GA, Gaede SE, Danielson GO 3rd, Gordon C, Stone MB. Two-level total disc replacement with Mobi-C cervical artificial disc versus anterior discectomy and fusion: a prospective, randomized, controlled multicenter clinical trial with 4-year follow-up results. J Neurosurg Spine. 2015 Jan;22(1):15-25. doi: 10.3171/2014.7.SPINE13953.

• Responsible Party: LDR Spine USA
• ClinicalTrials.gov Identifier: NCT00389597
• Other Study ID Numbers: LDR-001
• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Results First Submitted: January 3, 2014
• Results First Posted: May 1, 2014
• Last Update Posted: December 11, 2017