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Trial registered on ANZCTR


Registration number
ACTRN12618001375246
Ethics application status
Approved
Date submitted
25/05/2018
Date registered
16/08/2018
Date last updated
6/05/2019
Date data sharing statement initially provided
5/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
AUgmentation of the DIsc: Evaluating the safety and effectiveness of the Kunovus Disc Device (KDD) in maintaining disc height in subjects undergoing single level microdiscectomy for sciatica due to lumbar disc herniation.
Scientific title
A Multi-centre, Randomised, Single-Blinded, Twelve-Month Follow-Up Trial to Evaluate the Safety and Effectiveness of the Kunovus Disc Device for the Preservation of Lumbar Disc Height in Patients Undergoing Microdiscectomy for Sciatica due to Lumbar Disc Herniation
Secondary ID [1] 294994 0
Aus-KDD-MDP-002
Universal Trial Number (UTN)
U1111-1214-6813
Trial acronym
The AuDi Trial
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Lumbar Disc Herniation 308011 0
Intra-annular contained herniation 308012 0
Sub-ligamentous herniation 308013 0
Condition category
Condition code
Musculoskeletal 307049 307049 0 0
Other muscular and skeletal disorders
Surgery 308076 308076 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- The Kunovus™ System is a sterile system of medical instruments for spinal access and delivery of the nucleus implant materials to the annular cavity. The Kunovus™ System is a unique nested set of sterile device delivery instruments that allows for the deployment of the KDD via a single working cannula. This approach is tissue sparing and significantly less invasive than other disc replacement options. The Kunovus™ System is comprised of the following:
1) Disc Accessing Kit (DAK-01);
2) Sizing Unit Kit (SUK-01);
3) Pressure Generating Apparatus (PGA-01);
4) Delivery Instrumentation System - DIS Assembly (DIS-01);
5) Delivery Instrumentation System - Filler Tube / Static Mixer Assembly (DIS-02);
6) Filler Barrel Assembly (FBA);
7) Kunovus™ System Accessories: Extension Tubing, 3-Way Stopcock, Syringes, Guide Wire.

- This study consists of 8 visits over approximately 14-15 months.

- In this trial, patients will be randomly assigned to receive either the Kunovus Disc Device (KDD) with microdiscectomy or microdiscectomy alone. There is a 50% chance that they will receive microdiscectomy alone.

- The implantation procedure (if receive KDD with microdiscectomy) will be done by a team of expert Neurosurgeons/Orthopaedic spine surgeons. The duration of the procedure will be 3-4 hours.

- As with any investigational device, the specific risks are not fully known. However, the following are potential risks related to the KDD.
1) Failure of implant stability within the disc cavity or dislodgement or expulsion of implant
2) Possible allergic reaction to the materials (e.g. silicone) in the KDD;
Strategies to mange the potential risks:
1) At each study visit, safety will be assessed by evaluation of Adverse Event (AE)s, Serious Adverse Event (SAE)s, Unanticipated Adverse Device Effect (UADE)s, Treatment Emergent Adverse Event (TEAE)s, the incidence of device expulsion or migration, the incidence of device retrieval or attempted device retrieval and the incidence of repeat procedure(s) to the same herniated space. In the event of device failure, expulsion or migration and removal, the Investigator(s) is required to return the device according to the Sponsor’s written Device Retrieval Procedure for evaluation when possible. The investigator(s) is required to document the failure of the device as directed in the established AE reporting procedure.
2) Depending on a patient's allergies to medications, antibiotics may be used during and after the operation to help prevent infection.

Intervention code [1] 301336 0
Treatment: Surgery
Intervention code [2] 301337 0
Treatment: Devices
Comparator / control treatment
Patients undergoing routine microdiscectomy
Control group
Active

Outcomes
Primary outcome [1] 306022 0
The primary outcome is to evaluate the overall mean change in the Disc Height Index (DHI) as assessed by the Lumbar X-ray from baseline compared to one-year follow-up.

Timepoint [1] 306022 0
At 12 months following microdiscectomy surgery
Secondary outcome [1] 347380 0
The secondary outcome is to evaluate the 12-month safety of the KDD in the treatment of subjects undergoing single level microdiscectomy. The safety will be evaluated by the composite incidence and severity of AEs, ADEs, SAE’s, SADEs, USADEs, UADEs, TEAEs, the incidence of device expulsion or migration, the incidence of device retrieval or attempted device retrieval, and the incidence of repeat procedure(s) to the index intervertebral disc.

The safety will specifically be assessed by the following parameters:
- Treatment-related AEs, ADEs, SAEs, and SADEs
- Participant's medical records
- Physical examination
- Proportion of participants requiring a revision surgery
- Serum pregnancy test
- Urine pregnancy test
- Urine test
- Serum chemistry and haematology

All abnormal laboratory results will be reviewed and assessed for their clinical significance by an appropriately qualified Investigator. Results that fall outside the specified age-referenced range of values, and which are determined to be clinically significant, will be recorded as AEs/ADEs. Abnormal results will be followed up until they return to normal levels or are clinically stable.
Timepoint [1] 347380 0
At 12 months following microdiscectomy surgery

Eligibility
Key inclusion criteria
1. Subject must read and sign the Human Research Ethics Committee (HREC) approved Informed Consent Form (ICF) before any participation in the trial. Consent will be obtained before any trial-related procedures;
2. Subject aged between 21 to 80 years (inclusive) at the time of the screening and the baseline visits;
3. Subject must have a broad-based intra-annular contained herniation, sub-ligamentous herniation or frankly sequestrated LDH with associated back and buttock, posterior thigh and/or lower leg pain;
4. Subject must have no more than one level of LDH of an intervertebral disc in the lumbar spine region L3 to S1 as confirmed by Magnetic Resonance Imaging (MRI);
5. The Investigator must confirm subject as a suitable candidate for the treatment of the LDH via a microdiscectomy procedure;
6. The disc that is targeted for treatment must have a height of at least 8 mm in the centre as measured in the mid-sagittal plane;
7. Subject must be willing and able to complete trial required procedures and assessments and complete follow-up visit requirements for one year following the surgery;
8. Subject must be able to read and understand English or a language(s) for which a health-services accredited interpreter can administer the reported questionnaires/assessments and the ICF to the subject.
Minimum age
21 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has a known allergy to silicone or barium sulphate;
2. Subject has a history of osteoporosis, defined as a T-score of -2.5 or lower, confirmed by a Dual-Energy X-ray Absorptiometry (DEXA) scan completed within two years before the surgery;
3. Subject has more than one level of lumbar spinal disc herniation;
4. Subject has had prior lumbar surgery at any level;
5. Subject requires a spinal fusion of the herniated disc;
6. Subject has back or leg pain of non-spinal or unknown aetiology;
7. Subject has an implanted spinal cord stimulator;
8. Subject has a spinal deformity or disease of the spine, or any of the following: multiple sclerosis, cerebral palsy, spinal cord injury, tumour in the spine, motor neuron disease, arachnoiditis, or systemic inflammatory arthritis.
9. Subject has a Body Mass Index (BMI) > 40 kg/m2;
10. Subject has spondylolisthesis of the target disc that is more than Grade 1 and a disc height loss of more than 20% compared with the cephalad disc;
11. The subject is pregnant, lactating, or wishes to become pregnant within 12 months post surgery;
12. The subject is currently receiving workers compensation or in any litigation or confliction with third-party payers (including Motor Vehicle Accident insurers or the Centrelink);
13. Subject has an illness that decreases the probability of survival to the one-year trial endpoint;
14. The subject is expected to undergo a major elective spinal procedure during the duration of the trial;
15. The subject is currently participating or has participated in another investigational study within 30 days before signing the Informed Consent, or plans to participate in any other clinical research study while participating in this trial;
16. Subject has the evidence of active infection;
17. Subject has implanted pacemakers;
18. Subject with un-controlled epilepsy;
19. The subject does not meet the surgical eligibility criteria;
20. Subject with a condition or circumstance which, in the opinion of the Investigator, may put the subject at risk if he/she participates in the trial, may confound the trial results or may interfere with the subject’s participation in the trial

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer via an Interactive Web-based Response System (IWRS)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The first 2 subjects at each site will be roll-in subjects and will automatically be assigned to the KDD arm of the study. At this point, randomisation of subjects will be conducted via an IWS system using a 1:1 ratio to either receive the KDD with microdiscectomy or microdiscectomy alone.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Population Analysis:
The Intent-To-Treat (ITT) population consists of the entire cohort enrolled at the baseline visits. All effectiveness data will be analysed for the ITT population. The Safety Population consists of the ITT population excluding the control group. All safety analyses will be summarised for the Safety Population.

General Statistical Methods:
The primary analysis will be an ANCOVA for change in DHI from the baseline to the 12-month follow-up visits with factors for treatment and baseline score.
Missing data: For subjects who discontinue their participation before a specified time point, the last non-missing post-baseline observation will be carried forward (LOCF), with the baseline being carried forward if a subject has no post-baseline observations. Sensitivity analyses will be performed using observed cases only and using the baseline observation carried forward (BOCF).
Change from the baseline for NRS, ODI, and SF-36 scores will be analysed for both the arms of the trial.
AEs, ADEs, USADEs, TEAEs, SAEs, and UADEs related to the trial will be summarised by both overall incidences and by the severity for each treatment group.

Number of patients enrolled at first screening, and those who met the final eligibility criteria at the surgery will also be presented. Causes for ineligibility at the time of surgery will also be elaborated.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11000 0
St George Private Hospital - Kogarah
Recruitment postcode(s) [1] 22789 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 299579 0
Commercial sector/Industry
Name [1] 299579 0
Kunovus Pty Ltd.
Address [1] 299579 0
6/22 Belgrave Street, Kogarah, NSW 2217, Australia
Country [1] 299579 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Kunovus Pty Ltd.
Address
6/22 Belgrave Street, Kogarah, NSW 2217, Australia
Country
Australia
Secondary sponsor category [1] 298894 0
None
Name [1] 298894 0
N/A
Address [1] 298894 0
N/A
Country [1] 298894 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300481 0
Bellberry Limited
Ethics committee address [1] 300481 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 300481 0
Australia
Date submitted for ethics approval [1] 300481 0
31/08/2018
Approval date [1] 300481 0
24/04/2019
Ethics approval number [1] 300481 0

Summary
Brief summary
The overall objective of this study is to evaluate the KDD in maintaining disc height in subjects undergoing single level microdiscectomy as measured by DHI.
Trial website
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 83794 0
Dr Ashish Diwan
Address 83794 0
Suite 16, Level 5, St. George Private Hospital, 1 South St, Kogarah, NSW 2217, Australia
Country 83794 0
Australia
Phone 83794 0
+61 2 8566 716
Fax 83794 0
Email 83794 0
a.diwan@spine-service.org
Contact person for public queries
Name 83795 0
Dr Uphar Chamoli
Address 83795 0
Dr Uphar Chamoli; 6/22 Belgrave Street, Kogarah, NSW 2217, Australia
Country 83795 0
Australia
Phone 83795 0
+61 2 8387 7210
Fax 83795 0
Email 83795 0
uphar.chamoli@kunovus.com
Contact person for scientific queries
Name 83796 0
Dr Uphar Chamoli
Address 83796 0
Dr Uphar Chamoli; 6/22 Belgrave Street, Kogarah, NSW 2217, Australia
Country 83796 0
Australia
Phone 83796 0
+61 2 8387 7210
Fax 83796 0
Email 83796 0
uphar.chamoli@kunovus.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Ethical approval
Summary results
No Results