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Trial registered on ANZCTR


Registration number
ACTRN12611000646943
Ethics application status
Approved
Date submitted
9/10/2008
Date registered
23/06/2011
Date last updated
23/06/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A multi-center, prospective, randomised controlled trial comparing the efficacy and safety of PRODISC-C implant to anterior cervical discectomy and fusion (ACDF) surgery, in the treatment of symptomatic cervical disc disease (SCDD)
Scientific title
A multi-center, prospective, randomised controlled trial comparing the efficacy and safety of PRODISC-C (Registered Trade Mark) implant to anterior cervical discectomy and fusion (ACDF) surgery, in the treatment of symptomatic cervical disc disease (SCDD)
Secondary ID [1] 262433 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Symptomatic cervical disc disease (SCDD) 3804 0
Condition category
Condition code
Musculoskeletal 3986 3986 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ProDisc-C implant (replacement of diseased disc), Cervios (cage) for fusion post discectomy. These are two separate implants used for comparison in the trial. Subjects are randomised into either the ProDisc-C arm or the Cervios arm just prior to the surgery.

ProDisc-C is a device based on a ball and socket design. It is made up of 3 parts - the 1st is the inferior cobalt chromium molybdenum alloy plate with a midline keel which is anchored into the endplate of the inferior vertebral body. The 2nd component is an ultra high molecular weight polyethylene insert that is snap-locked into a tray detail in the inferior alloy plate and provides the inferior convex bearing surface. The 3rd component is a cobalt chromium molybdenum alloy plate with a midline keel that anchors to the superior vertebral body and has a highly polished concave bearing surface that articulates with the convex spherical dome.

The implant is permanent and surgical intervention is a one-off procedure, which requires 2 to 3 hours of surgery time.

After removal of the diseased cervical disc, the alternative procedure for PRODISC-C is the insertion of a device called a Cervios cage into the space to fuse the adjacent vertebrae together. Cervios is a radiolucent interbody fusion implant made of polyetheretherketone (PEEK) which has either a curved or wedge-shaped profile to fit into the inter-vertebral cervical disc space for anterior interbody fusion. The implant has a large round window in its middle to allow for bone through-growth or, the spacing can be packed with bone substitutes. The implant is conventionally referred to a "cage".

Compared to Cervios, the ball and socket design of ProDisc-C is for motion preservation, that is, the implant offers the potential of allowing for disc removal without increasing the stress and strain on adjacent cervical segments.
Intervention code [1] 3525 0
Treatment: Surgery
Intervention code [2] 236815 0
Treatment: Devices
Intervention code [3] 266807 0
Other interventions
Comparator / control treatment
Anterior Cervical Discectomy and Fusion (using Cervios)

The most common treatment to alleviate the pain and neurological deficits caused by degenerative disc disease is an anterior discectomy, which involves the surgical removal of soft disc herniations that press against the spinal nerve roots. Following cervical discectomy a bone graft is inserted into the disc space in order to fuse the adjacent vertebrae together. This is known as anterior cervical discectomy and fusion (ACDF).

Cervios is the comparator implant used in the trial to fuse the adjacent vertebrae together. ACDF is a simpler procedure which requires less surgery time since bone graft or Cervios insertion requires less surgical technique than ProDisc-C. However, ACDF procedures require postoperative immobilization of the neck and can result in abnormal loading of adjacent discs of the spine. Over time, these stresses may contribute to accelerated degeneration of the adjacent discs.
Control group
Active

Outcomes
Primary outcome [1] 4891 0
The primary endpoint is the overall success rates in the two treatment groups, to determine the device's effectiveness and safety for patients implanted with the ProDisc-C compared to ACDF.

Success is assessed by:
1. The patient's NDI score improves by at least 20% from baseline;
2. The patient's neurologic parameters (motor, senory and reflexes) are maintained or improved;
3. No removals, revisions, re-operations or additional fixation were required to modify any implant;
4. No adverse events occur which are probably or definitely related to the implant.

The potential medical risks associated with implanation of the ProDisc-C are unknown, but would be expected to be included in the general risks of anterior interbody treatments of the cervical spine including the following :

* Injury to the nerves including the nerve roots and spinal cord resulting in pain, weakness or paralysis;
* Dysphagia, dysphasia, dysphonia, fistula formation, tracheal, oesophageal and pharynheal perforation, dural tears and leasking of spinal fluid;
* Instability of the spine;
* Failure to restore or maintain intervertebral disc height;
* Implant migration, subsidence, loosening, disassembly or breakage that would require revision;
* Wear debris generation either plastic or metal leading to an adverse reaction of the local tissues that may either lead to implant loosening or failure;
* Failure of the implant to maintain or improve range of motion;
* Chance that the surgery will not reduce the pain or disability felt before the surgery and, in fact, the pain or disability may be worse than before.

Adverse events will be collected from -
* Monitoring visits when trial subjects' medical records are reviewed;
* Clinic assessments by the treating surgeon by reviewing X-rays and clinical diagnosis;
* Direct report from trial subjects.
Timepoint [1] 4891 0
At 24 months follow-up
Secondary outcome [1] 8257 0
The secondary endpoint is the incidence of adjacent disc disease in patients suffering from single level SCDD, over a 7 year period.

This outcome is assessed by X-rays and CT scans
Timepoint [1] 8257 0
Annually for 7 years post surgery
Secondary outcome [2] 276775 0
Analyses will be performed using data collected from the patient self-assessments of two Visual Analogue Scale (VAS) questionnaires (pain and satisfaction) and the SF-36 questionnaire.
Timepoint [2] 276775 0
Annually for 7 years post surgery

Eligibility
Key inclusion criteria
1.Subjects with symptomatic cervical disc disease (SCDD) in only one vertebral level between C3-C7 defined as:

Neck or arm (radicular) pain; and/or a functional / neurological deficit with at least one of the following conditions confirmed by imaging (Computed Tomography scans, Magnetic Resonance Imagings or X-rays)

-Herniated nucleus pulposus
-Spondylosis (defined by the presence of osteophytes)
-Loss of disc height
2.Unresponsive to non-operative treatment for approximately six weeks or has the presence of progressive symptoms or signs of nerve root compression in the face of conservative treatment.

3.Neck Disability Index (NDI) score greater than or equal to 15/50 (30%) (Considered moderate disability).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.More than one vertebral level requiring treatment (showing marked changes at a second level)
Marked cervical instability on resting lateral or flexion/extension radiographs:

a.translation greater than 3 mm and/or
b.greater than 11 degrees of rotational difference to that of either adjacent level .

2.Radiographic confirmation of severe facet joint disease or degeneration.

3.Known allergy to cobalt, chromium, molybdenum, titanium or polyethylene.

Clinically compromised vertebral bodies at the affected level(s) due to current or past trauma, e.g., by the radiographic appearance of fracture callus, malunion or nonunion.

4.Severe spondylosis at the level to be treated as characterized by any of the following:

- Bridging osteophytes;
- A loss of disc height greater than 70%
- Absence of motion (<2 degrees).

5.Neck or arm pain of unknown etiology.

6.Osteoporosis: A screening questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis Risk Estimation), will be used to screen patients who require
a Dual Energy X-ray Absorptiometry (DEXA) bone mineral density measurement. If DEXA is required, exclusion will be defined as a DEXA bone density measured T-score < -2.5 (The World Health Organization definition of osteoporosis. )

7.Paget’s disease, osteomalacia or any other metabolic bone disease (excluding osteoporosis which is addressed above).

8.Severe diabetes mellitus requiring insulin management

9.Pregnant

10.Active infection - systemic or local.

11.Taking medications or any drug known to potentially interfere with bone/soft tissue healing (e.g., steroids).

12.Rheumatoid arthritis or other autoimmune disease.

13.Systemic disease including AIDS, HIV, hepatitis.

14.Active malignancy: A patient with a history of any invasive malignancy (except non-melanoma skin cancer), unless he/she has been treated with curative intent and there have been no clinical signs or symptoms of the malignancy for at least 5 years.

15.Workers compensation or action compensation patients (at the surgeons discretion).

16.Subjects involved in other trials within the last month, prior to screening.

17.Subjects refused to agree to either ProDisc-C or Anterior Cervical Discectomy and Fusion (ACDF) treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Trial is explained to potential patients and friends/relatives, patient informatiion sheet given to patient to read and questions answered. Once consent form is signed, tests and questionnaires are carried out for eligibility. Patient will not know the treatment arm until after the operation. Surgeon will open the concealed opaque envelope when patient is under anaesthesia for the randomised treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be assigned a treatment, either PRODISC-C or ACDF surgery, according to a pre-determined blocked randomisation schedule. The randomisation schedule will be generated by Synthes. Subjects will be allocated a study number sequentially, each in a sealed opaque envelope that is supplied to the site. A total of 200 patients will be randomly assigned to PRODISC-C and 100 patients will be randomly assigned to ACDF treatment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/04/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment outside Australia
Country [1] 1252 0
China
State/province [1] 1252 0
Beijing
Country [2] 1253 0
Hong Kong
State/province [2] 1253 0
New Territories
Country [3] 1254 0
Korea, Republic Of
State/province [3] 1254 0
Seoul
Country [4] 1255 0
Singapore
State/province [4] 1255 0
Lower Kent Ridge Road
Country [5] 1256 0
Taiwan, Province Of China
State/province [5] 1256 0
Taipei

Funding & Sponsors
Funding source category [1] 3991 0
Commercial sector/Industry
Name [1] 3991 0
Synthes Asia Pacific
Country [1] 3991 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Synthes Asia Pacific
Address
Suite 1A, Level 3, Building 3,
20 Bridge Street,
Pymble, NSW 2073
Country
Australia
Secondary sponsor category [1] 3581 0
None
Name [1] 3581 0
Address [1] 3581 0
Country [1] 3581 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6066 0
Peking University Medical Ethics Committee
Ethics committee address [1] 6066 0
Peking University
Hadian District, Beijing 100083
People's Republic of China
Ethics committee country [1] 6066 0
China
Date submitted for ethics approval [1] 6066 0
22/02/2008
Approval date [1] 6066 0
28/02/2008
Ethics approval number [1] 6066 0
IRB approval reference : IRB00001052-08007

Summary
Brief summary
The PRODISC-C is intended to replace diseased and/or degenerated intervertebral discs of the cervical spine in patients with SCDD. PRODISC-C is intended to significantly reduce pain by allowing for the removal of the diseased disc while restoring disc height and providing the potential for motion at the affected vertebral segment.
The primary hypothesis of this study is that, in regard to key clinical outcomes, the PRODISC-C implant is not inferior (non-inferior) to ACDF surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29018 0
Address 29018 0
Country 29018 0
Phone 29018 0
Fax 29018 0
Email 29018 0
Contact person for public queries
Name 12175 0
Bernard Yau
Address 12175 0
Suite 1A, Level 3, Building 3,
20 Bridge Street,
Pymble, NSW 2073
Country 12175 0
Australia
Phone 12175 0
+61-2-94490400
Fax 12175 0
+61-2-94490499
Email 12175 0
[email protected]
Contact person for scientific queries
Name 3103 0
Dr Jack Zigler
Address 3103 0
Texas Beck Institute
6020 W. Parker Road,
Suite 200,
Plano, Texas 75093
Country 3103 0
United States of America
Phone 3103 0
+972-608-5000
Fax 3103 0
Email 3103 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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