Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001170910
Ethics application status
Approved
Date submitted
1/07/2020
Date registered
9/11/2020
Date last updated
13/04/2024
Date data sharing statement initially provided
9/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Single versus double hamstring tendon graft in anterior cruciate ligament (ACL) reconstruction in the paediatric patient
Scientific title
Single versus double hamstring tendon graft in anterior cruciate ligament (ACL) reconstruction in the paediatric patient: a single blind randomised controlled trial
Secondary ID [1] 301659 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
anterior cruciate ligament injury 318089 0
Condition category
Condition code
Surgery 316116 316116 0 0
Surgical techniques
Musculoskeletal 316118 316118 0 0
Normal musculoskeletal and cartilage development and function
Injuries and Accidents 316427 316427 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Procedure name: Single hamstring tendon ACL reconstruction
Approximate procedure duration: 1.5 hours
Two senior surgeons will perform all surgeries at the Queensland Children’s Hospital. Both have been allowed a surgical learning curve of 20 cases (minimum) before the start of the trial. Smith&Nephew (S&N) UltraButton + round ExtendoButton will be used.

Tendon harvest and graft preparation: The semitendinosus hamstring tendon be harvested for the single graft technique. A tendon stripper will be used to release the tendons from their proximal attachment via a standard push technique to a length of approximately 22cm. Graft preparation for the single hamstring technique will involve tripling the single semitendinosus tendon over two S&N UltraButton loops (with a round ExtendoButton being attached to the tibial UltraButton). The ends of the tendon complex are sutured via a whip-stitch technique using a #1 Ethibond suture on a J-needle. The prepared tendon complex will be set aside and soaked in a Vancomycin laden Raytec sponge. Once prepared, the graft is measured for both length (to ensure that the graft will adequately span the knee joint and sufficiently pass through both tunnels) and diameter (to determine the required femoral and tibial tunnel diameters for reaming).

Knee arthroscopy and tunnel drilling: These are comparable between interventions and therefore will not be elaborated here.

Graft passing and fixation: The nylon suture is pulled through the tibial tunnel so that the loop end is exiting out of the tibial tunnel. The graft is orientated and the Ethibond sutures are placed through the nylon loop. The Ethibond sutures are passed through the tibial and femoral tunnels and out of the skin of the anterolateral thigh. The arthroscope is placed into the knee joint and the Ultrabutton loop and graft are pulled into the femoral tunnel under vision to the line drawn on the graft from previous measurements. The Ultrabutton is toggled and flipped on the femoral side. The graft is held taught and the Femoral Ultraloop is reduced pulling the graft into the femoral tunnel to its desired length (~20mm). The knee is then brought out to 30-40 degrees flexion, and the tibial Ultraloop is reduced to pull the graft into the tibial tunnel. Final tensioning of the graft is done with knee extended to 0 degrees flexion the ExtendoButton is secured down to the tibia.

Post-operative care and rehabilitation: These are comparable between interventions and therefore will not be elaborated here.

Protocol adherence: A data monitoring committee will convene every 6 months to monitor post randomisation protocol adherence, patient safety and treatment efficacy during the surgical stage of the trial.
Intervention code [1] 317975 0
Treatment: Surgery
Comparator / control treatment
Procedure name: Double hamstring tendon ACL reconstruction
Approximate procedure duration: 1.5 hours
Two senior surgeons will perform all surgeries at the Queensland Children’s Hospital. Both have been allowed a surgical learning curve of 20 cases (minimum) before the start of the trial.. Smith&Nephew (S&N) Endobutton + Biosure Regenosorb screw will be used.

Tendon harvest and graft preparation: The semitendinosus + gracilis hamstring tendons will be harvested for the double graft technique. A tendon stripper will be used to release the tendons from their proximal attachment via a standard push technique to a length of approximately 22cm. Graft preparation will involve doubling the semitendinosus + gracilis tendons over one S&N Endobutton loop. The ends of the tendon complex are sutured via a whip-stitch technique using a #1 Ethibond suture on a J-needle. The prepared tendon complex will be wrapped with a soaked in a Vancomycin laden Raytec sponge and placed into the soft tissue tunnel where the hamstring tendons were harvested. Once prepared, the graft is measured for both length (to ensure that the graft will adequately span the knee joint and sufficiently pass through both tunnels) and diameter (to determine the required femoral and tibial tunnel diameters for reaming).

Knee arthroscopy and tunnel drilling: These are comparable between interventions and therefore will not be elaborated here.

Graft passing and fixation: The nylon suture is pulled through the tibial tunnel so that the loop end is exiting out of the tibial tunnel. The graft is orientated and the Ethibond sutures are placed through the nylon loop. The Ethibond sutures are passed through the tibial and femoral tunnels and out of the skin of the anterolateral thigh. The arthroscope is placed into the knee joint and the Endobutton loop and graft are pulled into the femoral tunnel under vision to the line drawn on the graft from previous measurements. The Endobutton is toggled and flipped on the femoral side. The graft is held taught with the Ethibond suture tails on the tibial side of the graft and, the knee is cycled through flexion/extension a number times and the knee is then brought out to 20-30 degrees flexion, the assistant is asked to secure the foot as well as place anterior directed force the distal femur. A wire is inserted behind the graft in the tibial tunnel and a Biosure Regenesorb screw is fully advanced and secured to fix the graft into the tibial tunnel.

Post-operative care and rehabilitation: These are comparable between interventions and therefore will not be elaborated here.

Protocol adherence: A data monitoring committee will convene every 6 months to monitor post randomisation protocol adherence, patient safety and treatment efficacy during the surgical stage of the trial.
Control group
Active

Outcomes
Primary outcome [1] 324316 0
Passive anterior-posterior knee laxity

Side-to side difference in anterior tibial translation will be measured by a GNRB® device attached to the patient’s leg, measuring tibiofemoral displacement in mm. Three measurements will be made on each knee, and the final value will be recorded as per the GNRB guidelines.
Timepoint [1] 324316 0
One year post surgery (primary timepoint), 2 and 5 years post surgery
Primary outcome [2] 324317 0
Graft failure incidence

Failure in this study will be defined as MRI confirmed ACL insufficiency, regardless of clinical or objective suspicions of laxity
Timepoint [2] 324317 0
One year post surgery (primary timepoint), 2 and 5 years post surgery
Secondary outcome [1] 384296 0
Limb length discrepancy will be measured from anterior-posterior standing long leg x-ray and will be classified as a difference of 1 cm between the operated and non-operated limbs
Timepoint [1] 384296 0
1, 2 and 5 years post surgery
Secondary outcome [2] 385020 0
Knee joint range of motion measured using a goniometer. The flexion or extension deficit will be calculated by subtracting the respective degrees of the operative knee from those of the contralateral knee
Timepoint [2] 385020 0
1, 2 and 5 years post surgery
Secondary outcome [3] 385021 0
Isokinetic strength evaluation at the knee

An isokinetic dynamometer (Humac NORM, MA, USA) will be used to evaluate knee flexion/extension concentric strength, as well as internal/external tibial rotation concentric strength on both the surgical and contralateral lower limbs. Testing will be performed on both the nonoperative and operative limbs, with the order of limb tested randomized to negate any fatigue effects. In addition to individual peak strength measurements, agonist/antagonist strength ratios will be calculated using the peak strengths for flexion/extension and internal/external tibial rotation.
Timepoint [3] 385021 0
1, 2 and 5 years post surgery
Secondary outcome [4] 385022 0
Quadriceps muscle tendon volume measured from segmented axial MRI of the quadriceps.
Timepoint [4] 385022 0
1, 2 and 5 years post surgery
Secondary outcome [5] 385023 0
Composite measure of graft morphology measured from MRI quantifying cross-sectional area within the tunnels and at the midpoint spanning the knee joint.
Timepoint [5] 385023 0
1, 2 and 5 years post surgery
Secondary outcome [6] 385024 0
The Pedi-IKDC composite score, an overall measure of patient reported pain, symptoms and functioning in daily and sport activities. This is a patient reported outcome measure collected from a questionnaire.
Timepoint [6] 385024 0
1, 2 and 5 years post surgery
Secondary outcome [7] 387671 0
Frontal plane angular malformation will be measured from anterior-posterior standing long leg x-ray and will be classified as a 3 degree difference between the operated and non-operated limbs.
Timepoint [7] 387671 0
1, 2 and 5 years post surgery
Secondary outcome [8] 387672 0
Quadriceps muscle anatomical cross sectional area measured from segmented axial MRI of the quadriceps.
Timepoint [8] 387672 0
1, 2 and 5 years post surgery
Secondary outcome [9] 387673 0
Quadriceps muscle tendon length measured from segmented axial MRI of the quadriceps.
Timepoint [9] 387673 0
1, 2 and 5 years post surgery
Secondary outcome [10] 387674 0
The KOOS Child composite score, an overall measure of patient reported pain, symptoms and functioning in daily and sport activities. This is a patient reported outcome measure collected from a questionnaire.
Timepoint [10] 387674 0
1, 2 and 5 years post surgery
Secondary outcome [11] 387675 0
The Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS). This composite score quantifies physical activity participation, This is a patient reported outcome measure collected from a questionnaire.
Timepoint [11] 387675 0
1, 2 and 5 years post surgery

Eligibility
Key inclusion criteria
All consecutive patients between the age of 8 and 18 who present to the orthopaedic outpatient’s clinic at the Queensland Children’s Hospital with an isolated ACL +/- meniscal injury
Minimum age
8 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Potential participants will be excluded if they have (1) concomitant posterior cruciate ligament injury, (2) collateral ligament instabilities of grade I or greater (2 to 5 mm), (3) bilateral ACL injury, (4) combined knee surgery with high tibial osteotomy or medial patellofemoral ligament, (5) evidence of early knee osteoarthritis on MRI, (6) previous knee surgery on the affected side, (7) chronic musculoskeletal conditions, (8) BMI > 35 and/or (9) booked for additional lateral tenodesis.

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)
Participants will be randomly allocated to a treatment group by the Griffith University randomization service. The randomization service will conceal group allocation from the study investigators until the participant has been enrolled and baseline data has been collected.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be stratified according to skeletal maturity and sex to minimize confounding bias and a randomly varied block size will be used to ensure participants are more evenly allocated throughout the entire trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size determination: Sample size calculations are estimated based on passive ACL laxity according to the pivot-shift test with grading in accordance with the International Knee Documentation Committee guidelines. Consistent with previous ACL surgery RCT’s the study is powered to reveal a difference of 1 grade on the pivot-shift test between the study groups, with a power of 80%. It was assumed that a side-to-side difference of 1 grade in the pivot test was clinically important and this will be support by a >3mm side-to-side difference in anterior-posterior laxity. The standard deviation of the pivot-shift test was estimated to be 1.5 grades. To reach a power of 80% (2-sided test at p<0.05), 36 patients were needed in each group. To increase the power of the study and to allow for 20% dropout at the primary time point, maximal tolerated level of dropout long term follow-up, 92 patients will be randomized.

Statistical analysis plan: Standard principles for RCTs will be followed, and primary analyses will be conducted using between-group comparisons on all participants on an intention-to-treat basis. There is a small risk that the surgeon may deem a harvested hamstring tendon inadequate for a single tendon graft (see safety consideration below) and therefore need to break randomisation. To account for this potential a secondary, per-protocol analysis will be used to assess the effect of treatment received and models will be adjusted for potentially confounding variables if necessary. The primary timepoint will be after 1 year on the quantitative anterior-posterior laxity results between the two surgery groups using general linear models. To determine between group differences at two- and five-years post-surgery we will employ mixed effects linear regression models with patients treated as a random effect, and time (1/2/5 years) and treatment group included as main effects and a time-by-treatment interaction included as fixed effects. For dichotomous outcomes, comparison will be by logistic regression models. Where continuous data does not meet linearity assumptions, as assessed by inspection of boxplots and the Shapiro-test it will be assessed using non-parametric methods such as median regression. Significance will be accepted at P<0.05. Sensitivity analyses to assess the effect of missing data will be undertaken on an outcome-by-outcome basis using MAR (multiple imputation) or NMAR (using pattern-mixture models) according to the pattern of the missing data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2021
Actual
14/09/2021
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
92
Accrual to date
66
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 17016 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 30683 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 306093 0
Charities/Societies/Foundations
Name [1] 306093 0
Children's Hospital Foundation
Country [1] 306093 0
Australia
Funding source category [2] 316296 0
Commercial sector/Industry
Name [2] 316296 0
Smith & Nephew Orthopaedics Ltd.
Country [2] 316296 0
United Kingdom
Primary sponsor type
Hospital
Name
Queensland Children's Hospital
Address
501 Stanley Street, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 306562 0
None
Name [1] 306562 0
Address [1] 306562 0
Country [1] 306562 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306313 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 306313 0
Ethics committee country [1] 306313 0
Australia
Date submitted for ethics approval [1] 306313 0
23/11/2020
Approval date [1] 306313 0
02/02/2021
Ethics approval number [1] 306313 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103470 0
A/Prof David Bade
Address 103470 0
7d, Level 7 Surgical Directorate
Queensland Children's Hospital
501 Stanley Street, South Brisbane QLD 4101
Country 103470 0
Australia
Phone 103470 0
+61 7 3068 4381
Fax 103470 0
Email 103470 0
[email protected]
Contact person for public queries
Name 103471 0
Julie Broom
Address 103471 0
7d, Level 7 Surgical Directorate
Queensland Children's Hospital
501 Stanley Street, South Brisbane QLD 4101
Country 103471 0
Australia
Phone 103471 0
+61 7 3068 4373
Fax 103471 0
Email 103471 0
[email protected]
Contact person for scientific queries
Name 103472 0
Christopher Carty
Address 103472 0
7d, Level 7 Surgical Directorate
Queensland Children's Hospital
501 Stanley Street, South Brisbane QLD 4101
Country 103472 0
Australia
Phone 103472 0
+61 7 3068 4382
Fax 103472 0
Email 103472 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IDP for all primary and secondary outcome measures will be available.
When will data be available (start and end dates)?
On completion of the primary endpoint and 5 years following completion of the final secondary timepoint.
Available to whom?
Available on request to the principle investigator. Each request will be considered on a case by case basis and sharing would generally require parties to enter into a data transfer agreement.
Available for what types of analyses?
For meta-analysis.
How or where can data be obtained?
Requests to be made to A/Prof Christopher Carty - [email protected]


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
SourceTitleYear of PublicationDOI
EmbaseSingle versus double hamstring tendon graft in anterior cruciate ligament reconstruction in the paediatric patient: A single-blind randomised controlled trial study protocol.2022https://dx.doi.org/10.1136/bmjopen-2021-057465
N.B. These documents automatically identified may not have been verified by the study sponsor.