Trial Outcomes & Findings for Study to Investigate the Performance of Cervical Arthroplasty for the Treatment of Cervical Degenerative Disc Disease (NCT NCT00700739)

NCT ID: NCT00700739

Last Updated: 2015-09-21

Results Overview

Overall success was a composite endpoint determined by the following clinical outcome measures: 1. Neck Disability Index ≥ 15-point improvement from baseline to 12 months post-operative, 2. No new clinically significant permanent abnormalities in neurological function (i.e. motor strength, nerve root tension signs, sensory and reflex signs) from baseline to 12 months post-operative, 3. No subsequent secondary surgical interventions (SSI) at the index level, and 4. No device-related serious events (dSAE) from intra-operative through 12-months post-operative. Please note that these time periods were intended to be from baseline to 24 months post-operative, but since the study was terminated early the 12 month time periods were utilized.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 60 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2015-09-21

Participant Flow

5 sites enrolled 60 subjects who were randomized into two treatment groups. Site 12 (17 subjects total) transferred into the Discover IDE study. Site 04 (5 subjects total) did not submit data, which was limited, due to EDC technical difficulties at the site. Therefore 38 subjects are reported in this study.

Participant milestones

Measure	Cervical Total Disc Replacement DISCOVER Artificial Cervical Disc	ACDF Anterior Cervical Discectomy and Fusion (ACDF)
Overall Study STARTED	22	16
Overall Study COMPLETED	18	12
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	Cervical Total Disc Replacement DISCOVER Artificial Cervical Disc	ACDF Anterior Cervical Discectomy and Fusion (ACDF)
Overall Study Lost to Follow-up	4	4

Baseline Characteristics

Study to Investigate the Performance of Cervical Arthroplasty for the Treatment of Cervical Degenerative Disc Disease

Baseline characteristics by cohort

Measure	Cervical Total Disc Replacement n=22 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=16 Participants Anterior Cervical Discectomy and Fusion (ACDF)	Total n=38 Participants Total of all reporting groups
Age, Continuous	45.3 years STANDARD_DEVIATION 8.87 • n=5 Participants	47.5 years STANDARD_DEVIATION 8.17 • n=7 Participants	46.2 years STANDARD_DEVIATION 8.65 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Spain	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Germany	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United Kingdom	20 participants n=5 Participants	14 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Overall Patient Success is composed of several outcome measures, some of which require a valid pre-operative and 12-month post-operative score. Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for the Overall Patient Success calculation.

Overall success was a composite endpoint determined by the following clinical outcome measures: 1. Neck Disability Index ≥ 15-point improvement from baseline to 12 months post-operative, 2. No new clinically significant permanent abnormalities in neurological function (i.e. motor strength, nerve root tension signs, sensory and reflex signs) from baseline to 12 months post-operative, 3. No subsequent secondary surgical interventions (SSI) at the index level, and 4. No device-related serious events (dSAE) from intra-operative through 12-months post-operative. Please note that these time periods were intended to be from baseline to 24 months post-operative, but since the study was terminated early the 12 month time periods were utilized.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Overall Patient Success	33.33 Percentage of subjects	90.91 Percentage of subjects

SECONDARY outcome

Timeframe: 12 months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The visual analogue scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 100 = 10 cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their neck.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Visual Analogue Scale (VAS) Neck Pain From Pre-treatment to 12 Months	-16.6 units on a scale Standard Deviation 34.2	-52.1 units on a scale Standard Deviation 22.86

SECONDARY outcome

Timeframe: 12 Months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The visual analogue scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 100 = 10 cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their left arm.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Visual Analogue Scale (VAS) Left Arm Pain From Pre-treatment to 12 Months.	-15.9 units on a scale Standard Deviation 25.7	-46.6 units on a scale Standard Deviation 43.5

SECONDARY outcome

Timeframe: 12 Months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The visual analogue scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0= 0 cm) listed on the left and 'Very severe pain' (score of 100= 10 cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their right arm.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Visual Analogue Scale (VAS) Right Arm Pain From Pre-treatment to 12 Months.	-18.4 units on a scale Standard Deviation 32.8	-20.5 units on a scale Standard Deviation 25.8

SECONDARY outcome

Timeframe: 12 Months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The visual analogue scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 100 = 10 cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their right shoulder.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Visual Analogue Scale (VAS) Right Shoulder Pain From Pre-treatment to 12 Months.	-15.7 units on a scale Standard Deviation 35.4	-22.4 units on a scale Standard Deviation 32.7

SECONDARY outcome

Timeframe: 12 Months

Population: Due to withdrawals and incomplete or unavailable assessments, 17 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The visual analogue scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 10 = 10 cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their left shoulder.

Outcome measures

Measure	Cervical Total Disc Replacement n=17 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Visual Analogue Scale (VAS) Left Shoulder Pain From Pre-treatment to 12 Months.	-17.1 units on a scale Standard Deviation 28.9	-49.8 units on a scale Standard Deviation 36.5

SECONDARY outcome

Timeframe: 12 months

Population: Due to withdrawals and incomplete or unavailable assessments, 16 subjects in the CTDR and 10 subjects in the ACDF treatment groups were available for this outcome.

The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into 2 summary measures that are scored from 0 to 100 (where 100 indicates the highest level of health) - the Physical Component Score (PCS-36) and Mental Component Score (MCS-36)

Outcome measures

Measure	Cervical Total Disc Replacement n=16 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=10 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 From Pre-treatment to 12 Months	4.1 units on a scale Standard Deviation 13.2	15.1 units on a scale Standard Deviation 14

SECONDARY outcome

Timeframe: 12 months

Population: Due to withdrawals and incomplete or unavailable assessments, 16 subjects in the CTDR and 10 subjects in the ACDF treatment groups were available for this outcome.

The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into 2 summary measures that are scored from 0 to 100 (where 100 indicates the highest level of health) - the Physical Component Score (PCS-36) and Mental Component Score (MCS-36)

Outcome measures

Measure	Cervical Total Disc Replacement n=16 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=10 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Physical Component Summary Quality of Life Measure Assessed by Short Form SF-36 From Pre-treatment to 12 Months	8.1 units on a scale Standard Deviation 11.7	17.7 units on a scale Standard Deviation 9.2

SECONDARY outcome

Timeframe: 12 months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 11 subjects in the ACDF treatment groups were available for this outcome.

The neck disability index (NDI) is a validated, disease specific, self-administrated questionnaire for assessing pain intensity and function in patients with neck pain on a scale from 0 to 100. A lower score is a better result (i.e. less severe pain and/or better function). The proportion of patients with an improved score (lower) of 15 points or more was the analysis variable.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=11 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Change in Function Assessed by Neck Disability Index Improvement From Pre-treatment to 12 Months	33.33 Percentage of Subjects	90.91 Percentage of Subjects

SECONDARY outcome

Timeframe: 12 months

Population: Due to withdrawals and incomplete or unavailable assessments, 18 subjects in the CTDR and 12 subjects in the ACDF treatment groups were available for this outcome.

The proportion of subjects with unrestricted work status (compared to subjects not working or with restricted work status) is reported at the 12 month follow-up interval.

Outcome measures

Measure	Cervical Total Disc Replacement n=18 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=12 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Work Status Assessed at 12 Months	38.89 Percentage of Subjects	50.00 Percentage of Subjects

SECONDARY outcome

Timeframe: 6 months

Population: Only 2 subjects in the Cervical Total Disc Replacement (cTDR) and 1 subject in the ACDF treatment groups were available for this outcome measure. There were 2 ACDF subjects at this endpoint, however one subject was missing the flexion extension rotation radiographic view therefore could not be included in the analysis.

Sagittal Angulation is a measure of the angle formed between the inferior endplate of the C2 vertebrae and the corresponding inferior endplate of vertebrae C7 of the spine, measured in degrees, from a side (sagittal) view.

Outcome measures

Measure	Cervical Total Disc Replacement n=2 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=1 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Sagittal Angulation, Also Known as Global Lordosis, Measured Radiographically at 6 Months	9.6 degrees Standard Deviation 10	-1.5 degrees Standard Deviation NA One ACDF subject was missing the flexion extension rotation radiographic view therefore could not be included in the analysis.

SECONDARY outcome

Timeframe: 24 months

Population: Study was terminated prior to 24 months therefore there are no results for this endpoint.

Adjacent Level Degeneration is evaluated using a point system that assigns numerical scores to severity of Height Loss, Anterior Osteophytes, and Endplate Sclerosis; and then grades into one of the following five categories: None, Mild, Moderate, Severe, or NA.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Population: Only 2 subjects in the cTDR and 1 subject in the ACDF treatment groups were available for this outcome measure. There were 2 ACDF subjects at this endpoint, however one subject was missing the flexion extension rotation radiographic view therefore could not be included in the analysis.

Maintenance of disc height is measured at the index and adjacent levels to determine the effect of the treatment on restoration or maintenance of the disc height. Initial post-operative disc height is compared with subsequent post-operative visits (i.e. 6 months) to evaluate the maintenance of disc height. The height is measured in millimeters (mm).

Outcome measures

Measure	Cervical Total Disc Replacement n=2 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=1 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Maintenance of Disc Height Measured Radiographically at 6 Months	4.7 mm Standard Deviation 0.57	5.1 mm Standard Deviation NA One ACDF subject was missing the flexion extension rotation radiographic view therefore could not be included in the analysis

SECONDARY outcome

Timeframe: 24 months

Population: The study was terminated prior to 24 months therefore there are no results for this endpoint.

Foraminal height is the maximum vertical distance, measured in millimeters (mm), between the inferior surface of the superior pedicle and superior surface of the inferior pedicle. These measurements are obtained via magnetic resonance imaging (MRI).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Population: Only 2 subjects in the cTDR and 2 subjects in the ACDF treatment groups were available for this outcome measure.

Cervical range of motion measures the angle, in degrees, between the inferior endplate of C2 to the inferior endplate of C7 on flexion-extension radiographs.

Outcome measures

Measure	Cervical Total Disc Replacement n=2 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=2 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Cervical Range of Motion Measured Radiographically at 6 Months	53.9 degrees Standard Deviation 16.4	55.2 degrees Standard Deviation 25.5

SECONDARY outcome

Timeframe: Intra-operatively to 24 months post-operative

The proportion of subjects with device related adverse events as reported throughout the duration of the study.

Outcome measures

Measure	Cervical Total Disc Replacement n=22 Participants DISCOVER™ Artificial Cervical Disc	ACDF n=16 Participants Anterior Cervical Discectomy and Fusion (ACDF)
Device Related Adverse Events	13.64 Percentage of subjects	0.00 Percentage of subjects

Adverse Events

Cervical Total Disc Replacement

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

ACDF

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cervical Total Disc Replacement n=22 participants at risk DISCOVER™ Artificial Cervical Disc	ACDF n=16 participants at risk Anterior Cervical Discectomy and Fusion (ACDF)
Infections and infestations Lower Respiratory Tract Infections	0.00% 0/22 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Musculoskeletal and connective tissue disorders Neck Pain	13.6% 3/22 • Number of events 3 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	0.00% 0/16 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Musculoskeletal and connective tissue disorders Pain in Extremity	4.5% 1/22 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	0.00% 0/16 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).

Other adverse events

Measure	Cervical Total Disc Replacement n=22 participants at risk DISCOVER™ Artificial Cervical Disc	ACDF n=16 participants at risk Anterior Cervical Discectomy and Fusion (ACDF)
Gastrointestinal disorders Dysphagia	4.5% 1/22 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Gastrointestinal disorders Faecal Incontinence	0.00% 0/22 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Injury, poisoning and procedural complications Fall	0.00% 0/22 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/22 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Musculoskeletal and connective tissue disorders Neck Pain	27.3% 6/22 • Number of events 6 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	12.5% 2/16 • Number of events 2 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Musculoskeletal and connective tissue disorders Pain in Extremity	4.5% 1/22 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Nervous system disorders Horner's Syndrome	0.00% 0/22 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).
Nervous system disorders Paraesthesia	4.5% 1/22 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).	6.2% 1/16 • Number of events 1 • Adverse Events were collected from the intra-operatively to 24 months post-operative timepoint (the patient with the longest follow-up for potential AE reporting was 24 months).

Additional Information

Mark Lotito

DePuy Synthes Spine

Phone: (508) 880-8045

Email: Mlotito@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee Clinical Investigators may freely present or publish results of the Clinical Investigation in a manner which fairly sets forth the conclusions reached by the Clinical Investigators, but only after DePuy has been given the opportunity of reviewing the proposed presentation or publication at least 30 days prior to the intended submission, presentation, or publication date.
• Publication restrictions are in place

Restriction type: OTHER