Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000762257
Ethics application status
Approved
Date submitted
1/05/2018
Date registered
7/05/2018
Date last updated
15/05/2023
Date data sharing statement initially provided
15/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Can Autologous Conditioned Plasma Therapy Enhance Hamstrings Healing After Anterior Cruciate Ligament Reconstruction?
Scientific title
Improving Donor Site Musculotendon Regeneration following Quadrupled Semitendinosus Anterior Cruciate Ligament Reconstruction through Autologous Conditioned Plasma Therapy
Secondary ID [1] 294658 0
None
Universal Trial Number (UTN)
U1111-1212-5151
Trial acronym
ACLR+Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anterior Cruciate Ligament Deficiency 307507 0
Condition category
Condition code
Musculoskeletal 306589 306589 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One group receives standard semitendinosus quadruple bundle Anterior Cruciate Ligament Reconstruction (ACLR), while the second group receives similar ACLR combined with Autologous Condition Plasma (ACP) administered to the donor site during surgery. The standard ACLR surgery group is referred to as "ACLR", whereas the group with ACLR combined with ACP is referred to as "ACLR+". For both groups, a quadruple bundle ipsilateral semitendinosus autograft is performed using an anteromedial portal technique. This is a standard surgical procedure to treat ACL deficiency and takes approximately 45 minutes. In the ACLR+ group, the surgical procedure will be augmented by application of Arthrex’ ACP therapy to the donor site and repairing the Sartorius fascia after harvest. The orthopaedic surgeon administers the ACP. For the ACP therapy, 10ml of the patient's own venous blood is aspirated and the syringe centrifuged in a proprietary closed unit (Arthrex Medical Company) for 5 minutes. The red blood cells are discarded, and the supernatant containing ACP (with additional CaCl to activate the ACP) is deposited onto the tendon excision site from pes anserinus to proximal terminus of excision. No adverse consequences are anticipated by using the ACP therapy.

Following surgery, all patients will be enrolled in a standardized physiotherapy program and will continue this treatment until completion (~6-9 months clinical recommendation). In the first month, participants will attend their own physiotherapist clinic for a minimum of two one-on-one sessions per week, with each session lasting one hour. For the remaining rehabilitation, participants are required to visit their physiotherapist at least once every two weeks for one hour. During this time, participants are expected to complete their physiotherapy exercises outside of the clinic and visit the physiotherapist for re-assessment.
The goal of the rehabilitation and exercises will vary depending on time after surgery. The first month of rehabilitation will involve restoring range of motion to the knee joint and strengthening of hamstring and quadriceps muscles (e.g., cycling). Months 2-3 include closed chain knee strengthening exercises (e.g., leg press) and isometric strengthening. The remaining rehabilitation will aim to restore balance through isokinetic and proprioception exercises, and eventually progress to functional movements such as running and jumping. In each phase, progression will be added by increasing resistance, increasing task complexity, and reducing stability. Adherence will be monitored for both groups through an electronic questionnaire.
Intervention code [1] 300955 0
Treatment: Surgery
Comparator / control treatment
In addition to the standard ACLR group serving as the control for the ACLR+ group, the unaffected contralateral limb serves as a secondary control for the affected limb within both groups. Thus, we will compare outcome measures at 1-year post-surgery (i.e., muscle function and knee health) both within participants (i.e., between affected vs unaffected limbs) and between surgery types (i.e., ACLR vs ACLR+). Participants who meet the inclusion criteria will be invited to attend the laboratory for testing 1-year post-surgery.
Control group
Active

Outcomes
Primary outcome [1] 334752 0
Bilateral and between-group differences in isometric knee flexion strength with the knee positioned at 60 degrees flexion on a seated motor driven dynamometer.
Timepoint [1] 334752 0
1-year post surgery.
Secondary outcome [1] 345840 0
Bilateral and between-group differences in Magnetic Resonance Imaging (MRI)-based measures of musculotendon volume, cross-sectional area, and length for semimembranosus, gracilis, sartorius, and biceps femoris bilaterally.
Timepoint [1] 345840 0
1-year following ACLR
Secondary outcome [2] 345841 0
Bilateral and between-group differences in passive anterior-posterior knee laxity using a KT-2000 arthrometer
Timepoint [2] 345841 0
1-year following Anterior Cruciate Ligament Reconstruction
Secondary outcome [3] 345842 0
Bilateral and between-group differences in patient-perceived knee function using the following questionnaires, Knee Injury and Osteoarthritis Outcome Score, Cincinnati Knee Rating System, and Knee Injury and Osteoarthritis Outcome Score (KOOS).
Timepoint [3] 345842 0
1-year following ACLR
Secondary outcome [4] 346416 0
Bilateral and between-group differences in passive semitendinosus fibre and distal aponeurosis kinematics at different joint angles assessed using ultrasound
Timepoint [4] 346416 0
1-year following ACLR
Secondary outcome [5] 346417 0
Bilateral and between-group differences in patient-perceived quality of life using the 36-item Short Form Health Survey (SF-36).
Timepoint [5] 346417 0
1-year following ACLR

Eligibility
Key inclusion criteria
• 18-50 years of age undergoing primary ACLR.
• The patient is able consent and participate fully in the intervention and follow-up testing.
• The patient is willing to follow the rehabilitation protocol established by the treating orthopaedic surgeon and referred physiotherapists.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Simultaneous multi-ligament repair/reconstruction.
• Utilization of graft other than semitendinosus on affected (possible intra-operative exclusion).
• Any revision ACLR.
• The patient is unable to consent or participate fully in intervention and follow-up testing.
• Any recent history of hamstring strain injuries within 6 months of ACL rupture diagnosis.
• Pre-existing symptomatic knee osteoarthritis.
• Medically diagnosed platelet disorder or haematological related disorder.
• Any other medical conditions likely to interfere with testing (at discretion of recruiters).
• Concomitant meniscus repair of lesions >1.5 cm or requiring post-operative bracing.

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)
The participating hospitals will receive a set of n (2:1 ratio, Pindara:Robina allocation based on historical flow rates of the participating surgeons) sequentially numbered and sealed envelopes which will contain the study identification number and treatment allocation. The site will open envelopes in consecutive order prior to incision on the day of surgery to determine treatment allocation. Blood is drawn, spun, and then the circulating nurse, surgical assistant or anesthetist will prepare syringe with ACP or, if allocated to control, discard blood and prepare saline for syringe. Syringe is wrapped in cotton to obscure contents from surgeon.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of trial participants will be achieved using a permuted block randomisation design. A block size of 4 will be used in conjunction with a random number sequence to create a master list for intervention allocation. The use of permutation blocks will assure the assignment of the intervention is balanced.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Nil.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
An a priori power analysis was performed using G*Power v3.1 (Universität Düsseldorf, Düsseldorf, Germany). To test the difference between two independent group means using a two-tailed test, a large effect size (d=0.86), and an alpha of 0.0531. On the basis of Nomura et al 2015, the effect size was calculated from the analysis of isometric knee flexion strength conducted on ACLR patients in compared with their healthy contralateral limbs at 60o knee flexion31. To achieve 80% power to detect differences in isometric knee flexion strength at 60o flexion between affected and unaffected limbs a total of 46 participants, split into two groups of 23, is required. To account for the 20% of patient withdrawal seen in surgical randomised controlled trials, a total of 54 participants will be recruited, split equally between each group (n=27). We will compare the differences between ACLR and intact contralateral limbs for the two groups (ACLR vs ACLR+) for all outcome measures using generalized linear models, and where possible make comparisons to the report by Konrath et al (2016).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/07/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 24737 0
Pindara Private Hospital - Benowa
Recruitment hospital [2] 24738 0
Robina Hospital - Robina
Recruitment postcode(s) [1] 22487 0
4217 - Benowa
Recruitment postcode(s) [2] 40359 0
4226 - Robina

Funding & Sponsors
Funding source category [1] 299275 0
Commercial sector/Industry
Name [1] 299275 0
Arthrex, Inc
Country [1] 299275 0
United States of America
Primary sponsor type
University
Name
Griffith University
Address
Office for Research, Gold Coast campus, Griffith University, QLD 4222 Australia
Country
Australia
Secondary sponsor category [1] 298544 0
None
Name [1] 298544 0
Address [1] 298544 0
Country [1] 298544 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300186 0
Griffith University Human Research Ethics Committee
Ethics committee address [1] 300186 0
Parklands Dr
Southport, QLD
4222
Ethics committee country [1] 300186 0
Australia
Date submitted for ethics approval [1] 300186 0
20/05/2018
Approval date [1] 300186 0
24/08/2018
Ethics approval number [1] 300186 0
2018/718
Ethics committee name [2] 313006 0
Royal Brisbane & Women’s Hospital Human Research Ethics Committee
Ethics committee address [2] 313006 0
Metro North
Hospital and Health Service
Butterfield St
Herston QLD 4029
Ethics committee country [2] 313006 0
Australia
Date submitted for ethics approval [2] 313006 0
01/12/2020
Approval date [2] 313006 0
03/03/2021
Ethics approval number [2] 313006 0
HREC/2021/QRBW/69253

Summary
Brief summary
Purpose and Hypothesis:
The purpose of this project is to examine whether Autologous Conditioned Plasma (ACP) therapy can enhance semitendinosus healing after Anterior Cruciate Ligament (ACL) reconstruction. Knee function and muscle-tendon regeneration will be compared 1-year post-surgery between a group receiving ACL reconstruction and a group receiving ACL reconstruction combined with Arthrex’ ACP application to the donor site.

Previous studies have found donor hamstring muscles experience substantial wasting (e.g., reduce in size and strength) following ACL reconstruction. Specifically, semitendinosus and gracilis muscles and muscle-tendons experience little regeneration, retraction of the muscle belly, atrophy, strength deficits, and impairments of function. We hypothesize ACL reconstruction combined with ACP application, referred to as “ACLR+”, will result in better muscle and tendon regeneration and improved knee function at 1 year following surgery.

Specifically, we hypothesize individuals receiving ACLR+ will have knee flexion strength more similar to their contralateral leg than those receiving standard ACLR. Further, we hypothesize individuals receiving ACLR+ will have muscle-tendon morphology (i.e., muscle-tendon volumes, lengths, and cross-sectional areas) similar to the muscles and tendons in the untreated contralateral leg. Conversely, those receiving standard ACL reconstruction will have a significantly smaller and lower quality donor muscle and tendons compared to the contralateral leg.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82838 0
Dr David John Saxby
Address 82838 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82838 0
Australia
Phone 82838 0
+61755528917
Fax 82838 0
Email 82838 0
[email protected]
Contact person for public queries
Name 82839 0
Dr David John Saxby
Address 82839 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82839 0
Australia
Phone 82839 0
+61755528917
Fax 82839 0
Email 82839 0
[email protected]
Contact person for scientific queries
Name 82840 0
Dr David John Saxby
Address 82840 0
Griffith University
Clinical Sciences 1, Gold Coast Campus, Parklands, Queensland, 4222
Country 82840 0
Australia
Phone 82840 0
+61755528917
Fax 82840 0
Email 82840 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidential. Ethical approval from institutions mandates confidentially is to be maintained.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.