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Trial registered on ANZCTR


Registration number
ACTRN12621000220864
Ethics application status
Approved
Date submitted
4/11/2020
Date registered
3/03/2021
Date last updated
3/03/2021
Date data sharing statement initially provided
3/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Autologous Protein Solution in the management of knee osteoarthritis
Scientific title
The effect of Autologous Protein Solution on patient reported outcomes in knee osteoarthritis
Secondary ID [1] 302512 0
none
Universal Trial Number (UTN)
U1111-1259-4651
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 319374 0
Condition category
Condition code
Musculoskeletal 317384 317384 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is an intra-articular injection of "autologous protein solution" produced from a patient's own blood via a provided centrifuge kit that involves separating and then concentrating the blood products.

60mls of blood is drawn from the patient. The resultant injection is approximately 3mls. This is injected in to the affected knee, immediately after it is drawn and processed (which takes about 20 minutes) using ultrasound guidance to confirm intra-articular placement, by one of the study doctors. It is a single administration
Intervention code [1] 318829 0
Treatment: Other
Comparator / control treatment
Intra-articular saline injection
Control group
Placebo

Outcomes
Primary outcome [1] 325420 0
WOMAC score

The first primary outcome will be osteoarthritis severity as rated by the overall WOMAC score between the two groups at each time period
Timepoint [1] 325420 0
1,3,6 and 12 months
Primary outcome [2] 326309 0
Koos pain subscore

The second primary outcome will be osteoarthritis pain severity as rated by the KOOS pain subscore score between the two groups at each time period
Timepoint [2] 326309 0
1,3,6 and 12 months
Primary outcome [3] 326310 0
KOOS ADL function subscore

The third primary outcome will be osteoarthritis functional impariment as rated by the KOOS ADL function score between the two groups at each time period
Timepoint [3] 326310 0
1, 3, 6, and 12 months
Secondary outcome [1] 387899 0
KOOS symptoms subscore

Osteoarthritis symptoms as rated by the KOOS symptoms subscore will be a secondary outcome.
Timepoint [1] 387899 0
1, 3, 6 and 12 months

Secondary outcome [2] 387900 0
VAS pain score

Osteoarthritis pain as rated by a VAS pain score will be a secondary outcome
Timepoint [2] 387900 0
1, 3, 6 and 12 months
Secondary outcome [3] 387901 0
Adverse events

The most common adverse event expected in transient joint pain/swelling after the injection. There is also the possibility of bruising from the taking of blood. The risk of introducing infection in to the joint (i.e. causing septic arthritis) is very low but is present and the patients will be informed of this and what to look out for.

Adverse events will be patient self reported - they will be asked to remain at the clinic for 30 minutes following the injection and report any symptoms prior to leaving, and advised to call the research assistant at any time if they observe an adverse event or have any concerns. They will also be asked at the time of the follow up surveys if they have noted any adverse events.
Timepoint [3] 387901 0
At the time of injection, 1, 3, 6 and 12 months
Secondary outcome [4] 391005 0
WOMAC pain subscore will be assessed as a secondary outcome (WOMAC overall score will be assessed as a primary outcome
Timepoint [4] 391005 0
1, 3, 6 and 12 months
Secondary outcome [5] 391006 0
Functional deficit from osteoarthritis will be assessed by WOMAC function subscore as a secondary outcome (WOMAC overall score will be assessed as a primary outcome)
Timepoint [5] 391006 0
1 ,3, 6 and 12 months
Secondary outcome [6] 392296 0
VAS function score

VAS function score will be assessed as a secondary outcome to reflect functional impairment from arthritis
Timepoint [6] 392296 0
1, 3, 6 and 12 months

Eligibility
Key inclusion criteria
Unilateral knee osteoarthritis
Kellgren-Lawrence grade 2-3
Failed at least one non-operative management
BMI <40
Minimum age
21 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Active infection
Osteoarthritis in the contralateral knee
Diagnosis other than osteoarthritis (e.g. inflammatory arthritis, gout, paget's disease, etc) in the affected knee
Other cause for pain as judged by the investigator (e.g. hip, spine pathology, acute injury)
Presence of surgical implants in the affected knee
Arthroscopic surgery on the affected knee within 6 months
Steroid injection in the affected knee within 3 months
Oral steroids within 2 weeks, or other systemic immunosuppressants within 6 weeks
Planned surgery on the affected knee
Local anaesthetic allergy
Current treatment for leakaemia or other malignancy


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)
Sealed opaque envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Statistical analysis will involve comparing the baseline demographics and radiographic severity between the two groups to ensure they are equal, using Chi-squared tests for absolute variables (gender, Kellgren-Lawrence classification of severity) and Independent T-test for continuous variables (age). We will use paired T-test to compare scores over the different timeframes within each cohort, and independent T-test to compare results between the two cohorts to determine if the APS injection is statistically superior to saline

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 outside Australia
Country [1] 23089 0
New Zealand
State/province [1] 23089 0

Funding & Sponsors
Funding source category [1] 306947 0
Charities/Societies/Foundations
Name [1] 306947 0
Northland Orthopaedic Research Trust
Address [1] 306947 0
15 Kensington Avenue
Kensington
Whangarei
0112
Country [1] 306947 0
New Zealand
Primary sponsor type
Government body
Name
Northland DHB
Address
Maunu Road
Private Bag 9742
Whangarei
0148
Country
New Zealand
Secondary sponsor category [1] 307715 0
None
Name [1] 307715 0
Address [1] 307715 0
Country [1] 307715 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307087 0
Health and Disability Ethics Committee
Ethics committee address [1] 307087 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 307087 0
New Zealand
Date submitted for ethics approval [1] 307087 0
18/11/2020
Approval date [1] 307087 0
16/12/2020
Ethics approval number [1] 307087 0
20/CEN/264

Summary
Brief summary
Pain and disability from knee osteoarthritis is a significant source of morbidity in the population. Intra-articular steroid, hyaluronic acid and platelet-rich protein have all been investigated for treatment of osteoarthitis. The autologous protein solution was developed as a biologic therapy that concentrates specific anti-inflammatory cytokines (particularly interleukin-1 receptor antagonist and soluble tumour necrosis factor-receptor I and II) as well as growth factors. Pre-clinical studies demonstrated high concentrations of these anti-inflammatory mediators, and low concentration of pro-inflammatory cytokines in the autologous protein solution. They demonstrated inhibition of MMP production (protease involved in cartilage degradation) and reduced cartilage breakdown products in vitro. An animal study demonstrated reduced lameness in horses. Small human trials have demonstrated an acceptable safety profile and improved patient reported outcome scores. We plan to assess the effect of a single APS injection on knee pain and function compared to placebo at 1, 3, 6 and 12 months
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105986 0
Dr Marla Ross
Address 105986 0
PO Box 1936
Shortland Street
Auckland
New Zealand

OR
Whangarei Hospital, Maunu Road, Private bag 9742, Whangarei 0148
Country 105986 0
New Zealand
Phone 105986 0
+64 21847165
Fax 105986 0
Email 105986 0
marlabennett@hotmail.com
Contact person for public queries
Name 105987 0
Dr Marla Ross
Address 105987 0
PO Box 1936
Shortland Street
Auckland
New Zealand

OR
Whangarei Hospital, Maunu Road, Private bag 9742, Whangarei 0148
Country 105987 0
New Zealand
Phone 105987 0
+64 21847165
Fax 105987 0
Email 105987 0
marlabennett@hotmail.com
Contact person for scientific queries
Name 105988 0
Dr Marla Ross
Address 105988 0
PO Box 1936
Shortland Street
Auckland
New Zealand

OR
Whangarei Hospital, Maunu Road, Private bag 9742, Whangarei 0148
Country 105988 0
New Zealand
Phone 105988 0
+64 21847165
Fax 105988 0
Email 105988 0
marlabennett@hotmail.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?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 9623 0
Study protocol
Citation [1] 9623 0
Link [1] 9623 0
Email [1] 9623 0
Other [1] 9623 0
Type [2] 9624 0
Informed consent form
Citation [2] 9624 0
Link [2] 9624 0
Email [2] 9624 0
Other [2] 9624 0
Type [3] 9625 0
Ethical approval
Citation [3] 9625 0
Link [3] 9625 0
Email [3] 9625 0
Other [3] 9625 0
Summary results
No Results