Study of the Safety and Effectiveness of the Artificial Cervical Disc - Low Profile Device at Two Adjacent Levels

A Prospective, Randomized, Controlled, Multicenter Pivotal Clinical Trial of the Artificial Cervical Disc-LP at Two Levels for Symptomatic Cervical Disc Disease

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00637156

Enrollment

397

Registered

2008-03-17

Start date

2006-06-30

Completion date

2018-02-01

Last updated

2018-05-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cervical Degenerative Disc Disease, Myelopathy, Radiculopathy

Keywords

Symptomatic DDD at Two Adjacent Levels of cervical spine

Brief summary

The purpose of this clinical investigation is to assess the safety and effectiveness of using the PRESTIGE-LP device in the treatment of patients with symptomatic degenerative disc disease at two adjacent levels of the cervical spine, with overall success being the primary endpoint of the clinical trial. The primary objective is to show non-inferiority of the investigational device to the control treatment. If non-inferiority is established, superiority will also be examined as the secondary objective.

Detailed description

This clinical investigation is being conducted to evaluate the PRESTIGE-LP device's performance at two adjacent cervical levels (C3-C7) in the treatment of patients with symptomatic degenerative disc disease. One-half of the patients in this randomized pivotal clinical trial will be treated at two adjacent cervical levels with the PRESTIGE-LP device. The remaining patients will receive a bi-level anterior cervical discectomy and fusion with cortical ring allografts and the ATLANTIS Cervical Plate System.

Interventions

DEVICEPRESTIGE LP device at two adjacent levels

PRESTIGE LP is a prosthetic device intended to replace a damaged disc in the cervical spine and intended to act as an intervertebral body spacer rather than a fusion device. It is inserted using an anterior surgical approach.

DEVICEBi-level fusion with ATLANTIS Cervical Plate System

Bi-level anterior cervical fusion procedure involving cortical ring allograft and the ATLANTIS Cervical Plate System.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Has cervical DDD at 2 adjacent cervical levels (C3-C7) requiring surgical treatment & involving intractable radiculopathy, myelopathy, or both * Has a herniated disc and/or osteophyte formation at each level to be treated that is producing symptomatic nerve root and/or spinal cord compression. The condition is documented by patient history, and the requirement for surgical treatment is evidenced by radiographic studies * Unresponsive to non-operative treatment for approximately 6 weeks or has the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management * Has no previous surgical intervention at the involved levels or any subsequent planned/staged surgical procedure at the involved or adjacent level(s) * Must be ≥ 18 years; skeletally mature at time of surgery * Preoperative NDI score ≥ 30 * Preoperative neck pain score ≥ 8 based on the preoperative Neck and Arm Pain Questionnaire * If a female of childbearing potential, patient is non-pregnant, non-nursing, and agrees not to become pregnant during the study period * Is willing to comply with the study plan and sign Patient Informed Consent Form

Exclusion criteria

* Has a cervical spinal condition other than symptomatic cervical DDD requiring surgical treatment at the involved levels * Has documented or diagnosed cervical instability relative to adjacent segments at either level, defined by dynamic (flexion/extension) radiographs showing: Sagittal plane translation \> 3.5 mm, or Sagittal plane angulation \> 20 degrees. * Has more than two cervical levels requiring surgical treatment * Has a fused level adjacent to the levels to be treated * Has severe pathology of the facet joints of the involved vertebral bodies * Has had previous surgical intervention at either one or both of the involved levels or at adjacent levels * Has been previously diagnosed with osteopenia or osteomalacia * Has any of the following that may be associated with a diagnosis of osteoporosis (If Yes to any of the below a DEXA Scan will be required to determine eligibility.) * Postmenopausal non-Black female over age of 60 who weighs \< 140 pounds * Postmenopausal female who has sustained a non-traumatic hip, spine, or wrist fracture * Male \> 70 years * Male \> 60 years who has sustained a non-traumatic hip or spine fracture * If the level of BMD is a T score of -3.5 or lower or a T score of -2.5 or lower with vertebral crush fracture, then the patient is excluded from the study * Has presence of spinal metastases * Has overt or active bacterial infection, either local or systemic * Has insulin dependent diabetes * Is a tobacco user who does not agree to suspend smoking prior to surgery * Has chronic or acute renal failure or prior history of renal disease * Has a documented allergy or intolerance to stainless steel, titanium, or a titanium alloy * Is mentally incompetent (If questionable, obtain psychiatric consult) * Is a prisoner * Is pregnant * Is an alcohol and/or drug abuser as defined by currently undergoing treatment for alcohol and/or drug abuse * Is involved with current or pending litigation regarding a spinal condition * Has received drugs that may interfere with bone metabolism within two weeks prior to the planned date of spinal surgery (e.g., steroids or methotrexate), excluding routine perioperative anti-inflammatory drugs * Has a history of an endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis imperfecta) * Has a condition that requires postoperative medications that interfere with the stability of the implant, such as steroids. (This does not include low-dose aspirin for prophylactic anticoagulation and routine perioperative anti-inflammatory drugs.) * Has received treatment with an investigational therapy within 28 days prior to implantation surgery or such treatment is planned during the 16 weeks following implantation

Design outcomes

Primary

Measure	Time frame	Description
Rate of Overall Success	24 Months	Rate of overall success is reported as the percentage of participants who met all of the following criteria: 1. Postoperative Neck Disability Index (NDI) score improvement of at least a 15-point increase from preoperative; 2. Maintenance or improvement in neurological status; 3. No serious adverse event classified as implant associated or implant/surgical procedure associated; and 4. No additional surgical procedure classified as a failure.

Secondary

Measure	Time frame	Description
Success Rate of Neurological Status	24 months	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 either remain the same or improve from the time of the preoperative evaluation to the time period evaluated.
Neck Pain Success Rate	24 months	Numerical rating scales were used to evaluate pain intensity and frequency. The pain score (0 min, 20 max) was derived by adding the numerical rating scores from the pain intensity (0-10, with a score of 0 representing no pain and a score of 10 representing pain as bad as it could be.) and frequency scales (0-10, with a score of 0 being pain none of the time and a score of 10 being pain all of the time). Neck pain success rate is reported as the percentage of participants whose neck pain improvement met the following criterion: Preoperative Score - Postoperative Score \> 0.
Arm Pain Success Rate	24 months	Numerical rating scales were used to evaluate pain intensity and frequency. The pain score (0 min, 20 max) was derived by adding the numerical rating scores from the pain intensity (0-10, with a score of 0 representing no pain and a score of 10 representing pain as bad as it could be.) and frequency scales (0-10, with a score of 0 being pain none of the time and a score of 10 being pain all of the time). Arm pain success rate is reported as the percentage of participants whose arm pain improvement met the following criterion: Preoperative Score - Postoperative Score \> 0.
Success Rate of SF-36 PCS	24 months	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 of SF-36 PCS was defined as: Post Score - Pre Score \>= 0. The Success rate of SF-36 PCS is reported as the percentage of the participants who were classified as a success for SF-36 PCS.
Success Rate of SF-36 MCS	24 months	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 of SF-36 MCS were defined as: Post Score - Pre Score \>= 0. The Success rate of SF-36 MCS is reported as the percentage of the participants who were classified as a success for SF-36 MCS.
Rate of Disc Height Success	24 months	Disc height was assessed by determining the Functional Spinal Unit (FSU) height. The rate of disc height success is reported as the percentage of participants whose disc height for each level based on either the anterior or posterior measurements met the following criterion: Postoperative Height - 6 Week Postoperative Height \>= -2mm
Gait Success Rate	24 months	Patient's gait was assessed by using Nurick's classification, and indicated either as normal or graded on a scale of 0 to 5. Success was defined as maintenance or improvement in the postoperative status as compared to the preoperative condition: Preoperative Score - Postoperative Score \>= 0. The gait success rate is reported as the percentage of participants who had gait success.
Operative Time	Time of operation, an average of 1.7-2.1hrs	Operative time was recorded from skin incision to wound closure.
Success Rate of Neck Disability Index	24 months	Success rate of Neck Disability Index is reported as the percentage of participants whose neck disability index score met the following criterion: Pre-treatment Score - Post-treatment Score ≥ 15.
Hospital Stay	From admission to discharge, an average of 1.0-1.5 day	—
Rate of Secondary Surgery at Index Level	24 months	Secondary surgical procedures at the index level included revisions, removals, supplemental fixations and reoperations. Rate of secondary surgery at index level is reported as percentage of subjects who had secondary surgeries at index level.
Change of Neck Disability Index Score From Baseline	Baseline and 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). Change of NDI was defined as NDI at 24 month minus NDI at baseline.
Change of Neck Pain Score From Baseline	Baseline and 24 months post-operation	Numerical rating scales were used to evaluate neck pain intensity and frequency. Subjects rated 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, subjects recorded 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 (0 to 20) was the addition of pain intensity and frequency scores. Change of neck pain score was defined as neck pain score at 24 months minus neck pain score at baseline.
Change of Arm Pain Score From Baseline	Baseline and 24 months post-operation	Numerical rating scales were also used to evaluate arm pain intensity and frequency. Subjects rated 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, subjects recorded 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 (0 to 20) was the addition of pain intensity and frequency scores. Change of arm pain score was defined as arm pain score at 24 months minus arm pain score at baseline.
Change of General Health Status -- SF-36 PCS From Baseline	Baseline and 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 were summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for PCS was between 0 and 100, with higher scores denoting better quality of life. Change of SF-36 PCS score was defined as PCS score at 24 months minus PCS score at baseline.
Change of General Health Status -- SF-36 MCS From Baseline	Baseline and 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 were summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for MCS was between 0 and 100, with higher scores denoting better quality of life. Change of SF-36 MCS score was defined as MCS score at 24 months minus MCS score at baseline.
Blood Loss	During the time of operation, an average of 1.7-2.1 hrs	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
PRESTIGE LP Device PRESTIGE LP device at two adjacent levels: PRESTIGE LP is a prosthetic device intended to replace a damaged disc in the cervical spine and intended to act as an intervertebral body spacer rather than a fusion device. It is inserted using an anterior surgical approach.	209
ATLANTIS Cervical Plate System Bi-level fusion with ATLANTIS Cervical Plate System: Bi-level anterior cervical fusion procedure involving cortical ring allograft and the ATLANTIS Cervical Plate System.	188
Total	397

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	0	1
Overall Study	Lost to Follow-up	10	16
Overall Study	Withdrawal by Subject	0	7

Baseline characteristics

Characteristic	PRESTIGE LP Device	ATLANTIS Cervical Plate System	Total
Age, Continuous	47.1 years STANDARD_DEVIATION 8.3	47.3 years STANDARD_DEVIATION 7.7	47.2 years STANDARD_DEVIATION 8
Alcohol Used No	93 participants	100 participants	193 participants
Alcohol Used Yes	116 participants	88 participants	204 participants
BMI	28.2 kg/m^2 STANDARD_DEVIATION 5.6	28.6 kg/m^2 STANDARD_DEVIATION 4.9	28.4 kg/m^2 STANDARD_DEVIATION 5.3
Education Level <High school	21 participants	20 participants	41 participants
Education Level >High school	125 participants	104 participants	229 participants
Education Level High school	63 participants	64 participants	127 participants
Height	67.2 inches STANDARD_DEVIATION 3.9	67.6 inches STANDARD_DEVIATION 4	67.4 inches STANDARD_DEVIATION 3.9
Marital Status Divorced	32 participants	23 participants	55 participants
Marital Status Married	146 participants	133 participants	279 participants
Marital Status Separated	4 participants	2 participants	6 participants
Marital Status Single	25 participants	29 participants	54 participants
Marital Status Widowed	2 participants	1 participants	3 participants
Preoperative Work Status No	63 participants	75 participants	138 participants
Preoperative Work Status Yes	146 participants	113 participants	259 participants
Race/Ethnicity, Customized Asian	1 participants	3 participants	4 participants
Race/Ethnicity, Customized Black	8 participants	8 participants	16 participants
Race/Ethnicity, Customized Caucasian	195 participants	172 participants	367 participants
Race/Ethnicity, Customized Hispanic	4 participants	4 participants	8 participants
Race/Ethnicity, Customized Other	1 participants	1 participants	2 participants
Sex: Female, Male Female	117 Participants	98 Participants	215 Participants
Sex: Female, Male Male	92 Participants	90 Participants	182 Participants
Unresolved Spinal litigation No	209 participants	187 participants	396 participants
Unresolved Spinal litigation Yes	0 participants	1 participants	1 participants
Weight	182.1 lbs STANDARD_DEVIATION 42.6	186.3 lbs STANDARD_DEVIATION 37.2	184.0 lbs STANDARD_DEVIATION 40.1
Worker's Compensation No	183 participants	169 participants	352 participants
Worker's Compensation Yes	26 participants	19 participants	45 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	191 / 209	171 / 188
serious Total, serious adverse events	72 / 209	90 / 188

Outcome results

Primary

Rate of Overall Success

Rate of overall success is reported as the percentage of participants who met all of the following criteria: 1. Postoperative Neck Disability Index (NDI) score improvement of at least a 15-point increase from preoperative; 2. Maintenance or improvement in neurological status; 3. No serious adverse event classified as implant associated or implant/surgical procedure associated; and 4. No additional surgical procedure classified as a failure.

Time frame: 24 Months

Population: The primary analysis dataset for this study included all subjects who received study devices and completed the initial surgical procedures. The analysis was based on the observed data and missing data due to lost-to-follow-ups were imputed. For the primary endpoint, the analysis consists of 199 investigational subjects and 160 control subjects.

Arm	Measure	Value (NUMBER)
PRESTIGE LP Device	Rate of Overall Success	81.4 percentage of participants
ATLANTIS Cervical Plate System	Rate of Overall Success	69.4 percentage of participants

Comparison: The null hypothesis H0: p1 + d ≤ p0, and the alternative hypothesis is Ha: p1 + d \> p0 where P0 and P1 are the overall success rates in the control group and the investigational group respectively, and d is the non-inferiority margin. The analyses used Bayesian methodology. Should the posterior probability P(p1 - p0 \> -d \| data) be at least 0.95, then the null non-inferiority hypothesis will be rejected, and non-inferiority of the investigational device to the control will be claimed.p-value: 195% CI: [0.022, 0.201]Bayesian model

Comparison: Superiority comparison of overall success rates in two treatment groups was a secondary objective of this trial. Superiority analysis was performed if non-inferiority was demonstrated. If the posterior probability is at least 0.95, a claim of superiority can be made.p-value: 0.993Bayesian model

Secondary

Arm Pain Success Rate

Numerical rating scales were used to evaluate pain intensity and frequency. The pain score (0 min, 20 max) was derived by adding the numerical rating scores from the pain intensity (0-10, with a score of 0 representing no pain and a score of 10 representing pain as bad as it could be.) and frequency scales (0-10, with a score of 0 being pain none of the time and a score of 10 being pain all of the time). Arm pain success rate is reported as the percentage of participants whose arm pain improvement met the following criterion: Preoperative Score - Postoperative Score \> 0.

Time frame: 24 months

Population: For this endpoint, the analysis consists of subjects in the primary analysis dataset with evaluable arm pain success status at 24 months, which leads to 199 subjects in the investigational group and 159 subjects in the control group.

Arm	Measure	Value (NUMBER)
PRESTIGE LP Device	Arm Pain Success Rate	88.9 percentage of participants
ATLANTIS Cervical Plate System	Arm Pain Success Rate	89.9 percentage of participants

Comparison: The null hypothesis H0: p1 + d ≤ p0, and the alternative hypothesis is Ha: p1 + d \> p0 where P0 and P1 are the arm pain success rates in the control group and the investigational group respectively, and d is the non-inferiority margin. The analyses used Bayesian methodology. Should the posterior probability P (p1 - p0 \> -d \| data) be at least 0.95, then the null non-inferiority hypothesis will be rejected, and non-inferiority of the investigational device to the control will be claimed.p-value: 0.99795% CI: [-0.073, 0.056]Bayesian model

Comparison: Superiority comparison of arm pain success rates in two treatment groups was performed if non-inferiority was demonstrated.p-value: 0.395Bayesian model

Secondary

Blood Loss

Time frame: During the time of operation, an average of 1.7-2.1 hrs

Arm	Measure	Value (MEAN)	Dispersion
PRESTIGE LP Device	Blood Loss	67.2 ml	Standard Deviation 64.1
ATLANTIS Cervical Plate System	Blood Loss	55.7 ml	Standard Deviation 46.3

Comparison: Superiority comparison of the blood loss in two treatment groups was assessed.The null hypothesis is H0: μ1 = μ0 and the alternative hypothesis is Ha: μ1 ≠ μ0, where μ0 and μ1 denote the mean in control group the investigational group, respectively. Should the posterior probability of superiority P(μ1- μ0 \< 0\|data) be at least 97.5%, the superiority would be claimed.p-value: 0.0295% CI: [0.56, 22.44]Bayesian model

Secondary

Change of Arm Pain Score From Baseline

Numerical rating scales were also used to evaluate arm pain intensity and frequency. Subjects rated 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, subjects recorded 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 (0 to 20) was the addition of pain intensity and frequency scores. Change of arm pain score was defined as arm pain score at 24 months minus arm pain score at baseline.