Optimizing GRAft SElection for ACL Reconstruction (GRASE-ACL Trial) - a Three-armed Randomized Controlled Trial
Phase: NA
Conditions: ACL - Anterior Cruciate Ligament Rupture
Sponsor: Hvidovre University Hospital

 
 
 
Optimizing GRAft SElection in ACL reconstruction - a randomized 
controlled clinical trial  
Acronym: GRASE ACL 
{1} 
 
PROTOCOL CONTRIBUTORS 
 Merete Brink Speedtsberg1,2,3, cand. scient. hum. fys. 
Co-study Director, Ph.D. fellow  
Cecilie Køllner Olsen2, cand. med 
Co-study Director, Ph.D. fellow 
Per Hölmich2, Professor  
Investigator, main supervisor  
Mette Kreutzfeldt Zebis3,4, Professor  
Investigator, main co-supervisor  
Kristoffer Barfod2, Professor  
Investigator, co-supervisor 
Jesper Bencke1,2, Phd  
Investigator, co-supervisor  
Thomas Kallemose6,  
Statistical consultant  
Lars Louis Andersen5, Professor 
Scientific advisor 
 
AFILLIATIONS {5a} 
1. Human Movement Analysis Laboratory, Department of Orthopaedic Surgery, Amager-Hvidovre Hospital, 
Copenhagen University Hospital, Copenhagen, Denmark. 
2. Sports Orthopedic Research Center-Copenhagen (SORC-C), Department of Orthopedic Surgery, 
Copenhagen University Hospital Amager-Hvidovre, Kettegård Allé 30, 2650 Hvidovre, Denmark. 
3. Department of Midwifery, Physiotherapy, Occupational Therapy and Psychomotor Therapy, University College 
Copenhagen, Faculty of Health, Copenhagen, Denmark. 
4. Institute of Sports Medicine Copenhagen, Bispebjerg and Frederiksberg Hospital, Copenhagen University 
Hospital, Copenhagen, Denmark. 
5. National Research Centre for the Working Environment, DK-2100, Copenhagen, Denmark  
6. Department of Clinical Research, Copenhagen University Hospital, Amager-Hvidovre, Denmark 
 

 
 
 
PROTOCOL DETAILS 
This protocol is developed according to SPIRIT guidelines 1 and the Revised Cochrane risk-of-bias tool 
for randomized trials (RoB 2) 2. 
The numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers.   
 The order of the items has been modified to group similar items, as recommended by the TRIALS 
journal 3. 
 
SITE AND SPONSOR   
{5b} 
 Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Denmark. 
Contact for trial sponsor: Merete Brink Speedtsberg1,2,3, cand. scient. hum. fys. Co-study Director, 
Ph.D. fellow {5b}. 
Email: grase-acl.amager-og-hvidovre-hospital@regionh.dk,  
 Tel: +45 26711334, visiting address: Hvidovre Hospital, section 333, Kettegaard Alle 30, Hvidovre, 
Denmark. 
 
TRIAL REGISTRATION  
{2a, 2b} 
 ClinicalTrials.gov registration and protocol repository{2a,2b}: NCT05342441 
The Regional Committee on Health Research Ethics – Capital Region of Denmark: H-19001194 
 
FUNDING  
{4} 
Novo Nordic Foundation – Surgical Grant, 2021  
                             Grant ID [NNF21OC007211   
Private Danish family foundation  
 
 
Grant ID [24080042] 
   
(Foundation name may not be publicly disclosed for administrative reasons; no conflicts of interest or ethics to declare 
Internal Copenhagen University Hospital, Amager-Hvidovre Research funds, 2022 
 
TRIAL STATUS 
Inclusion for the trial is currently at 147 patients per 08-08-25  
 

 
 
 
VERSION  
{3} 
MAIN PROTOCOL REVISION HISTORY 
Version 
Date  
 
1.0  
2019-01-07 
• First draft submitted to ethical 
review board (Regional 
Committees on Health Research 
Ethics for The Capitol Region). 
1.1  
2021-09-17 
• Second draft (full protocol with 
embedded statistical analysis 
plan) with approval identifiers 
from the Capital Region Data 
Protection Agency, Denmark and 
the Regional Committees on 
Health Research Ethics for The 
Capitol Region, Denmark 
(Identifyer: H-19001194) 
1.2  
2022-04-04 
Registration submitted at 
ClinicalTrials.gov - registration 
identifier (NCT05174182). 
1.4  
2025-13-08-25 
• Full protocol submitted as 
supplementary document to 
ClinicalTrials.gov registration  
Table 1 – Overview of protocol versions. 
 
CLINICAL TRIALS.GOV REVISIONS 
Clinical trials version 
Date submitted 
Changes 
2 
2022-05-27 
Study status: Study start altered from April 14th to May 9th  
3 
2023-09-20 
Study status: Record verification 
4 
2025-04-15 
Study status: Record verification 
 
Oversight: Product manufactured in and exported from the U.S 
noted at NO. 
5 
 
Full protocol including all ethically approved changes 
submitted. 
 
Primary Completion (Estimated): Altered to 2026-9-30 
 
Enrollment (Estimated) : Altered to 160 
Table 2 – overview of revisions to study registration at clinicaltrials.gov 
 
 
 

 
 
 
REVISIONS TO REGISTRATION AT THE REGIONAL COMMITTEE ON HEALTH RESEARCH 
ETHICS – CAPITAL REGION OF DENMARK 
Clinical trials version 
Date submitted 
Changes 
2 
2020-12-07 
Administrative information: Title change  
 
Intervention: BPTB was added as third arm to the planned trial 
to justify the clinical application and relevance of the study.  
Power calculation:  
 
Power calculation: Updated to enable superiority analysis with 
three-way comparisons, resulting in 150 projected patients.  
 
Timeline: Extended by a year due to changed inclusion.  
 
Outcomes: Muscle morphologic changes altered from primary 
outcome to secondary outcome. 
3 
2022-05-05 
Administrative information: Title change  
 
Timeline: Extended to 2027-12-30 due to Covid-19 delays and 
national nurse strike.  
 
Funding: Surgical Grant from Novo Nordic  
4 
2022-10-10 
Recruitment strategy: Project team permission to review 
patients in the inpatient clinic for eligibility and inform 
responsible surgeon.  
 
Measurements: Collection of X-ray imaging as the clinical 
routine imaging was not sufficient.  
5 
2025-06-03 
Inclusion: Number of included participants increased to 160 to 
ensure a minimum of 50 in each group, with the possibility of 
more in two others due to stratified randomization. 
 
Funding: Anonymous family foundation                                                    
(no conflicts of interest or ethics) 
Table 3 - Overview of revisions to study registration at the regional committee on health research 
ethics – capital region of Denmark 
 
APPENDICES AND SUPPLEMENTARY  
Appendix 1: Clinical knee examination protocol  
Appendix 2: Biomechanical protocol  
Appendix 3: Medical imaging protocols 
Appendix 4: Bi-Weekly monitoring via text-messages (Danish)  
Appendix 5: Ethical approval documents: Written participant information (Danish) {32}, Informed 
consent forms (Danish) {24}. 
 
 

 
 
 
Abbreviations 
GRASE ACL – Optimizing GRAft SElection in ACL reconstruction 
SPIRIT – Standard Protocol Items: Recommendations for Interventional Trials 
RoB 2 – Revised Cochrane Risk of Bias Tool for Randomized Trials 
BPTB – Bone–Patellar Tendon–Bone (graft) 
HT – Hamstring Tendons (graft) 
QT – Quadriceps Tendon (graft) 
ST/Gr – Semitendinosus and Gracilis (hamstring tendons used in graft) 
ACL – Anterior Cruciate Ligament 
ACLR – Anterior Cruciate Ligament Reconstruction 
RCT – Randomized Controlled Trial 
NKR – National Clinical Guidelines (Denmark) 
RTD – Rate of Torque Development 
PROM – Patient-Reported Outcome Measure 
IKDC – International Knee Documentation Committee (evaluation form) 
LSI – Limb Symmetry Index 
RTD Rate of Torque Development  
PICOT – Population, Intervention, Comparison, Outcome, Time (research framework) 
PASS – Patient Acceptable Symptom State 
KNEES-ACL – Knee Numeric-Entity Evaluation Score for Anterior Cruciate Ligament Injuries 
ACL-RSI – Anterior Cruciate Ligament – Return to Sport after Injury (scale) 
TSK-11 – Tampa Scale for Kinesiophobia  
WORQ – Work Rehabilitation Questionnaire  
HRQoL – Health-Related Quality of Life 
EQ-5D – EuroQol 5-Dimensions  
PRECIS-2 – PRagmatic-Explanatory Continuum Indicator Summary tool (version 2) 
WP – Work Package 
MVIC– Maximal Voluntary Isometric Contraction  
EMG – Electromyography 
 

 
 
 
PLRI – Posterolateral Rotatory Instability 
MRI – Magnetic Resonance Imaging 
ICRS – International Cartilage Repair Society (cartilage damage grading) 
RoM – Range of Motion 
CONSORT – Consolidated Standards of Reporting Trials 
ITT – Intention-to-Treat 
MCID – Minimal Clinically Important Difference 
MDD – Minimal Detectable Difference 
BMJ – British Medical Journal 
GCP – Good Clinical Practice 
LBK – Lovbekendtgørelse (Danish Consolidated Act – context: Patient Compensation Act) 
ICMJE – International Committee of Medical Journal Editors 
SORC-C – Sports Orthopedic Research Center – Copenhagen 
 
 
KEYWORDS 
Anterior Cruciate Ligament Reconstruction, Graft Selection, Randomized Controlled Trial, Patient-
Reported Outcomes, Neuromuscular knee control 
 
RECRUITMENT:  
Start:  
 
May 9th, 2022  
Anticipated termination:  
August 30th, 2025  
 
 
 
 
 
 

 
 
 
BACKGROUND 
{6a} 
Rupture of the anterior cruciate ligament (ACL) is a common sports-related knee injury that primarily 
affects young, active individuals 4,5. The ACL plays a crucial role in knee stability 6 and ACL rupture 
leads to pain, reduced function 7–11, and an increased risk of subsequent injuries and osteoarthritis 12–
14, significantly impacting long-term quality of life 15,16.  
ACL reconstruction (ACLR) is the primary surgical treatment to restore knee stability 17,18, enable return 
to physical activity, and mitigate the risk of subsequent injuries 19. However, recovery is often 
prolonged, functional deficits can persist for years, and only around half of patients regain their pre-
injury activity levels 20. 
Graft selection plays a pivotal role in ACLR outcomes, as different options vary in tissue properties, 
graft integration, and donor site morbidity, such as pain and muscle strength deficits 21–23. Surgeons 
base their decisions on expertise, patient-specific factors, and the clinical outcomes associated with 
each graft type 9. However, the lack of consensus on the optimal graft type has led to significant 
variability in surgical practices among institutions. 
 
CURRENT GRAFT CHOICES 
{6b} 
The primary graft options for ACLR are autografts, which are commonly harvested from the patellar 
tendon with bone plugs (BPTB), hamstring tendons (HT), or quadriceps tendon with or without bone 
plug (QT). 
 
PATELLAR TENDON WITH BONE PLUGS (BPTB) 
 
BPTB autografts were once considered the gold standard for ACLR due to several advantages, 
including ease of harvest, consistent graft size and strength, and rapid graft incorporation facilitated by 
bone-to-bone healing. These factors contribute to low graft failure rates and minimal post-operative 
laxity. However, donor site morbidity remains a significant drawback, with anterior knee pain reported 
in up to 52% of patients two years after surgery and reduced extensor strength often contributing to 
functional deficits 9. 
According to the 2024 Danish ACL Reconstruction Registry, the use of BPTB grafts has declined, 
representing 3.4% of primary ACL reconstructions in 2023 compared to 9,2% in 2005-2022 4. 
 
HAMSTRING TENDONS (HT) 
HT autografts, comprising the semitendinosus and gracilis tendons, are associated with reduced rates 
of anterior knee pain 21,24,25 and fewer complications involving the extensor mechanism compared to 
BPTB grafts 26. However, donor site morbidity for HT grafts includes sensory deficits from saphenous 
nerve disruption and strength deficits in the harvested muscles, affecting knee flexion and internal 
rotation 27–29. These deficits are of biomechanical concern, as the semitendinosus contributes to knee 

 
 
 
stabilization and ACL protection 30,31. Additionally, HT grafts have been linked to greater knee laxity and 
higher graft failure and revision rates than BPTB grafts 32–35. 
Preparation techniques for HT grafts include doubling the semitendinosus and gracilis tendons (ST/Gr 
autograft) or using a quadrupled semitendinosus tendon, which aims to limit loss of hamstring 
strength 36. While patient-reported outcomes between these methods and other techniques show no 
significant differences, outcomes on pain, hamstring strength, and knee laxity remain inconsistent, 
warranting further long-term studies 37. 
In Denmark, HT was used in 66.5% of primary ACLR in 2023. The quadruple semitendinosus increased 
from 8.2% in 2005-2022 to 24.2% in 2024, while the use of doubled tendons slightly declined to 42.3% 
in 2024 from 69.9% in 2005-2022 4. 
 
QUADRICEPS TENDON (QT)  
QT autografts have gained popularity due to robust graft size and tissue properties 38,39, reduced 
anterior knee pain compared to BPTB grafts 38,40–45, and the advantage of preserving hamstring function 
46. They also demonstrate comparable or superior outcomes in PROMs, knee stability, graft failure, and 
revision rates relative to HT grafts 38,40–45,47–53.  
Introduced in 1979, QT autografts initially faced skepticism due to early studies reporting inferior 
outcomes for partial-thickness grafts, and additionally, early clinical outcomes from 2000 to 2010 
were mixed, with concerns about postoperative pivot shift and prolonged knee extension weakness. 
However, subsequent research with larger cohorts and higher evidence levels have yielded more 
positive results 9,38. In Denmark, QT grafts saw a temporary decline in use around 2020 due to reports 
of higher revision rates, later attributed to the surgical learning curve, as high-volume institutions 
reported revision rates comparable to other graft types 35,54,55. 
Despite these advancements, QT autografts have certain limitation, including a higher risk of patellar 
fractures when harvested with a bone block 38, potential extensor weakness persisting up to two years 
postoperatively 56, and a limited amount of high-quality evidence supporting their use. 
In 2023, QT autografts accounted for 18.1% of primary ACL reconstructions in Denmark in 2024 (9.3% 
were performed without a bone block 4), which is an increase from the period between 2005-2022 
(6%).  
 
GAPS IN LITERATURE (NEED FOR A TRIAL) 
The literature on QT grafts in ACLR remains in its early stages, with limited data from randomized 
controlled trials (RCTs). Most systematic reviews compare only two graft types at a time, thereby 
limiting the scope for comprehensive evaluations of all three principal autograft options. Additionally, 
heterogeneity in study design, follow-up durations, reported outcomes, and patient demographics 
further complicate direct comparisons. Consequently, the most recent Danish National Clinical 
Guidelines (NKR) were not able to provide definitive recommendations on the preferred graft 57. 
Another gap in the literature is the limited focus on strength deficits by graft type. Flexion strength is 
more affected in HT grafts, while extension strength is more impacted in BPTB and QT grafts 58,59. 

 
 
 
Research often attributes poor outcomes to quadriceps deficits and hop-test performance without 
adequately addressing hamstring function or its relationship with quadriceps strength 60–62. Given the 
critical role of hamstring activation in ACL protection during cutting movements63, further research is 
warranted to elucidate its impact on reconstruction outcomes. 
Rate of torque development (RTD), a measure of neuromuscular performance 64,65, is essential for 
assessing readiness to return to sport and reducing re-injury risk, as injuries frequently occur during 
the initial milliseconds of movement 64,66. However, research linking RTD to graft choice remains 
limited. Studies on HT grafts suggest persistent RTD deficiencies 64,67, but no studies have directly 
compared HT grafts with other graft types 68. The biomechanical changes caused by graft harvest and 
their impact on outcomes such as PROMs and knee function also remain poorly understood. 
This study aims to address these gaps by analyzing a uniform cohort within the same timeframe, 
enabling direct comparisons across graft types. To date, only one RCT has compared all three major 
autograft options. The study included 75 patients and was powered to detect differences in knee laxity. 
It found no significant differences 69. In contrast, this study is designed to assess more comprehensive 
outcomes, including International Knee Documentation Committee (IKDC) scores and RTD, providing 
critical data to optimize graft selection. 
 
OBJECTIVES & HYPOTHESIS 
{7} 
The overall aim of the GRASE ACL trial is to investigate and compare the effect of graft selection in ACL 
reconstruction using a comprehensive holistic research approach. The trial is designed to ensure a full 
reporting of consequences and effects from a patient-reported, movement biomechanical, clinical 
and muscle morphological perspectives. To meet this ambition and owed to the scale of the trial, two 
primary objectives have been formulated to reflect different aspects of treatment efficacy. This dual 
approach captures both subjective recovery and objective functional performance.  
The research questions answered by the objectives follow the PICOT model 70.  
 
PRIMARY OBJECTIVES:  
1: The primary objective 1 is patient-centered to evaluate the effect of graft selection on patient-
reported outcome measures, primarily investigated as the International Knee Documentation 
Committee Evaluation Form score (IKDC). 
The research question answered by this objective is:                                                                                                         
Is ACL reconstruction surgery using the QT graft non-inferior to the BPTB- and ST/Gr grafts on patient-
reported knee function 12 months postoperatively in adult men and women with primary ACL rupture.                            
This objective will be evaluated using a non-inferiority approach, with the hypothesis that the QT graft 
will show non-inferior IKDC scores at 12 months compared to the ST/Gr and BPTB grafts. 

 
 
 
2: The primary objective 2 is centered in movement biomechanics to evaluate the effect of each graft 
on neuromuscular control of the knee, primarily investigated as the limb symmetry of rate of torque 
development (RTD-LSI) in isometric knee extension and knee flexion. 
The research question answered by this objective is:                                        
 
        
Is the consequences from graft harvest on neuromuscular control of the knee (RTD-LSI) greater in 
ST/Gr grafts than QT- and BPTB grafts 12 months postoperatively in adult men and women.                   
This objective will be assessed using a superiority approach, with the main hypothesis that the ST/Gr 
graft will show the lowest performance on RTD-LSI in knee flexion compared to the BPTB and QT grafts.                          
Secondary to this the differences between grafts in RTD-LSI in both knee extension and knee flexion is 
investigated is tested using pairwise comparisons.   
 
SECONDARY OBJECTIVES  
Compare effect of graft selection on secondary and exploratory patient-reported, clinical, and 
biomechanical outcomes of improvement and adverse effects at 12 months postoperatively  
Compare effect of graft selection on secondary and exploratory patient-reported, clinical, 
biomechanical and medical imaging outcomes of improvement and adverse effects at secondary 
timepoints at 1 and 6 months, and at long-term follow-up after 24months (table 4-5).  
Explore factors associated with effect moderation or mediation of primary or long-term secondary 
outcomes to determine who will potentially experience benefits or harm from different grafts.  
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
TRIAL DESIGN, REPORTING, AND CONDUCT  
{8}  
This study is a single-center assessor-blinded randomized controlled trial with a three-group parallel 
design. Patients are randomly assigned to ACL reconstruction using either the BPTB, ST/Gr, or QT graft, 
with a 1:1:1 allocation ratio.  
The reporting of the results will adhere to the CONSORT (Consolidated Standards of Reporting Trials) 
guidelines for reporting 71. 
To increase the transparency and validity, we have posted this protocol as a timestamped pre-print 
publication to the ClinicalTrials.gov repository before termination of patient inclusion and prior do data 
analysis as a supplementary to the registration. 
 
FRAMEWORK 
As described in objectives, the study was conducted with two parallel however, interdependent 
objectives.  
Objective 1 was designed and powered from a non-inferiority framework as the QT graft represents the 
option least utilized historically, but in high growth in the clinical community (KILDE ÅRSRAPPORTER).  
 Objective 2 was designed and powered from a superiority framework. The ST/gr graft has shown higher 
risk of re-rupture in the literature. As it has been established that semitendinosus activity is protective 
of the ACL 31, the design and analysis plan reflect this association expressed in evaluation of RTD-LSI. 
The superiority framework in the statistical analysis further allows three-way comparisons, which is 
important as this objective is a new perspective in a surgical RCT investigating graft choice.  
 
TWO-GROUP PARALLEL-ARM DESIGN  
This design was chosen to include the three most utilized grafts in Denmark and internationally to give 
the study higher clinical relevance and validity for patients and clinicians.            
It allows for three-way comparisons and, has higher external validity than other designs, and incurs 
fewer statistical issues 72. 
 
PRAGMATIC FRAMEWORK: 
Using the PRECIS-2 tool (PRagmatic-Explanatory Continuum Indicator Summary) for categorizing our 
trial, we found our design to be mostly pragmatic with a total score 37 of 45 73. Some domains, in terms 
of patient eligibility and follow-up are the least pragmatic (fig. 1). 
Also, neuromuscular control may seem more explanatory in nature but is considered very relevant to 
patients in terms of evaluation of effect at 12 months before being cleared for sports participation. 
 

 
 
 
 
Fig. 1  - Visualization of the PRECIS-2 item scores of the GRASE ACL trial.  
 
 
PATIENT AND PUBLIC INVOLVEMENT 
The research questions, outcome measures, and study design were drafted by the research team 
based on clinical expertise and existing literature. Seven patients with previous ACL-R fulfilling the 
inclusion criteria were asked to complete the full set of questionnaires. The patients were 
subsequently interview about the amount of follow-up visits and the number and selection of PROMs. 
The study team plans to share the results with participants and relevant patient communities, 
ensuring that the findings are accessible and informative. 
 
 
 

 
 
 
METHODS: PARTICIPANTS, INTERVENTIONS AND OUTCOMES 
STUDY SETTING 
{9} 
Data collection, including recruitment, surgeries, and follow-ups are conducted at the Arthroscopic 
Centre and HuMAn Lab, Amager-Hvidovre University Hospital, Capital Region, Denmark. 
 
RECRUITMENT STRATEGY 
{15} 
Patients will be recruited consecutively from the operating list for ACL reconstruction at Amager-
Hvidovre University Hospital (fig. 2). Recruitment strategies include direct outreach during and after 
preoperative consultations.  
All patients signed up for ACL reconstruction during the study’s timeframe will be screened for 
eligibility by the surgeon as first contact. If eligible and interested in receiving further information, the 
surgeon provides the written information and obtains consent for a project staff member to contact 
the patient for further information. The participant is given >48 hours consideration time before being 
contacted by project staff, at which time they can decline further information even they accepted it 
previously with the surgeon.  
For patients who meet eligibility criteria but choose not to participate, the reasons for declining, will be 
recorded anonymously. This information will be used for post-hoc analyses to assess population 
characteristics and potential bias. 
 
CONSENT 
{26a, 26b} 
Informed consent will be obtained from all participants by trained clinical personnel prior to any study-
related procedures. The consent process will provide comprehensive written and oral details regarding 
the study’s purpose, procedures, risks, and benefits, ensuring that participants can make an informed 
decision about their participation.  
Patients are informed about their rights as study participants provided by the National Committee on 
Health Research Ethics. The consent forms, written in clear and understandable Danish, have been 
reviewed and approved by the Ethics Committee. 
The patient is further informed of our data protection agreement stating that all information captured 
is confidential, and that their data will be stored according to current laws and regulations. 
 
 

 
 
 
KEY ELIGIBILITY CRITERIA 
{10} 
INCLUSION CRITERIA 
 
Age 18-40 years. 
 
First-time ACL rupture. 
 
Injury sustained within the last 2 years. 
 
Activity level with a Tegner score ≥ 3 prior to ACL rupture. 
 
Personal goal of returning to an activity level of Tegner score ≥ 3. 
EXCLUSION CRITERIA 
 
Concomitant knee ligament injury (apart from MCL grade I-II). 
 
Non-Danish speakers. 
 
BMI > 30. 
 
Previous severe injury to either knee. 
 
Prior severe injury to quadriceps, hamstrings, or patella tendon. 
 
Prior bone fracture involving the articular surfaces of the femur and tibia.  
 
Medical conditions preventing participation. 
 
MRI verified meniscus or cartilage damage according to criteria below. 
EXCLUSION CRITERIA DURING INITIAL ARTHROSCOPY 
 
Medial or lateral meniscus resected to less than 50%. 
 
Meniscus treatment requiring more restrictive rehabilitation than usual care (e.g., root lesion 
or complete radial tear). 
 
Cartilage damage ≥ ICRS grade 3 involving more than 2 cm². 
 
 
RATIONALE FOR POPULATION 
The study includes adult patients with primary ACL rupture referred to surgical reconstruction.  
The age between 18-40 was decided upon as young patient are most likely to sustain re-injurie after 
reconstruction 74, and this age group make up the largest representation of patients with ACL injuries 
in Denmark 75. It was decided that the intervention was of a magnitude that it would not be ethical to 
accept informed consent from patients below the legal age in Denmark (<18). Previous ACL rupture, 
other severe injuries to either knee, and large concomitant meniscus, cartilage or bone injuries in the 
index knee would all exclude the patient from the study. These prior or concomitant injuries would 
interfere with the limb symmetry indices (healthy leg) and would most likely reduce the preoperative 
state and the outcome trajectory on the reconstructed knee.  
Required activity level was set to follow the clinical practice, where surgery may be indicated due to 
work life requirements or sustained laxity and reduced control of the knee. To this end we allowed a 
two-year period from injury to surgery and previous attempts with conservative treatment.   
 

 
 
 
 
fig. 2 – Inclusion flow 
 
ALLOCATION  
{16a, 16b, 16c} 
Participants will be allocated to graft type following a sequence generated using a computer-based 
randomization schedule with permuted blocks of three and six in randomized order (REDCap). Small 
blocks have been permuted to avoid skewed allocation towards the end on inclusion, where a 
minimum allocation has been determined according to sample size. Stratification factors include 
biological sex and age to ensure balanced groups.  
Allocation is concealed using opaque, sealed envelopes, managed by an unblinded project associate 
who will provide the envelope to the surgeon. The envelope may only be unsealed in the operating 
room when the final perioperative exclusion criteria are assessed.   
 

 
 
 
SAMPLE SIZE  
{31c} 
As the trial has been designed with two primary objectives, a sample size calculation has been 
performed on both primary objectives which are described below. The final sample size has been 
scaled for the primary outcome requiring the most patients. To allow for potential dropout and 
maintain robust analysis, the study plans to recruit 50 patients for each group. To ensure this, 
inclusion will continue until 50 patients have been included in each group. 
PRIMARY OBJECTIVE 1 
The literature suggests a minimal clinically important difference (MCID) between 7-13 points 76,77 with a 
standard deviation of 12 points 76. To test non-inferiority between groups (A vs. C, A vs. B, and B vs. C) 
with a non-inferiority margin of 7 points and a standard deviation of 12 points, a sample size of 37 
participants per group is required. This sample size ensures 80% power to detect that no group is 
worse than the others within the predefined margin at a significance level of 0.05.  
LSI-RTD OUTCOME 
A local unpublished pilot study showed a minimal detectable difference (MDD) of 12% with a standard 
deviation of 17%. Although the minimal clinically important difference is unknown, the MDD of 12% 
guides the analysis. Detecting an effect size of 0.71 (12/17) with 80% power and significance level 
0.0167 (Bonferroni correction for multiple testing) requires 44 participants per group.  
 
BLINDING 
{17a} 
Outcome assessors are blinded to group allocation, to reduce bias. Prior to each patient visit, elastic 
sports tape will be placed over the areas where possible incisions would be placed depending on 
which graft is used to conceal the donor graft site. It is not possible to blind the assessor to injured and 
healthy knee due to the nature of the injury making it perceptibly obvious. 
 
UNBLINDING  
{17b} 
Blinding of patients and surgeons is not feasible or ethical due to the nature of the intervention. 
However, the surgeon is not involved in any postoperative assessment of the participants, and the 
patients are instructed not to reveal to the assessor, what graft has been used for the reconstruction.  
A project associate may discuss cases with clinical personnel when necessary for clinical decision-
making, but these discussions will not involve the outcome assessors. Unblinding is necessary for 
clinical reasons, scientific logistics and monitoring of termination of inclusion.   
The unblinded project associate is responsible for inclusion of perioperative information from the 
patient medical chart. The unblinded treating surgeon is involved in clinical knee outcomes prior to 
randomization and perioperative registration of graft characteristics after randomization is revealed.  

 
 
 
INTERVENTIONS 
{11a} 
ACL reconstruction is performed as usual care with the deviation from the randomization process and 
that two specialized surgeons (regardless of seniority) will be present for each procedure to maintain 
consistency and reduce variability. 
 
PREOPERATIVE PREPARATION 
The surgical procedures will be performed by a team of specialized and experienced surgeons from 
the Arthroscopic Center at Hvidovre Hospital, ensuring standardized procedures across patients. The 
procedure begins with standard preoperative preparation, including time-out to confirm the surgical 
plan and administration of prophylactic antibiotics. Under anesthesia, the knee is evaluated to 
confirm positive Lachman and pivot shift tests, ensuring no signs of combined instability. 
 
SURGICAL PROCEDURES  
{11a, 11b} 
Diagnostic arthroscopy is initiated using two anterior portals, with systematic inspection of the knee. 
Cartilage and meniscus conditions are evaluated and managed as appropriate. Meniscal lesions are 
either left untreated, resected, or repaired to restore stability. The ACL is confirmed to be ruptured. 
If the patient does not present with any exclusion criteria during this initial arthroscopy, the 
randomization will be performed, and the ACL reconstruction will continue according to the assigned 
graft type. In case of adverse effects with graft preparation, the surgeon was allowed to deviate from 
assigned graft, but the patient remained included per intention to treat.   
 
BPTB GRAFT 
The central 10 mm of the patellar tendon with 20-30 mm bone plugs from the tibia and patella are 
harvested. Both the femoral and tibial tunnels are anatomically placed in the native footprint of the 
ACL 78. The graft is secured proximally with a Milagro screws (DePuy Synthes) and, after 
preconditioning and in 30deg of flexion, with a Milagro screws (DePuy Synthes) distally. 
 
ST/GR GRAFT 
Harvest of gracilis and semitendinosus tendons via a 4-5 cm incision at the pes anserinus, prepared 
as a four-strand graft. Both the femoral and tibial tunnels are anatomically placed in the native 
footprint of the ACL 78. The graft is secured with resorbable RIGIDFIX® Curve Cross Pin System (DePuy 
Synthes) proximally and, after preconditioning and in 30deg of flexion, with a Milagro screws (DePuy 
Synthes) distally. 
 

 
 
 
QT GRAFT 
Harvest of the central portion of the quadriceps tendon through a 4-5 cm transversal incision at the 
upper pole of the patella. A 10-12 mm wide and 6 mm deep graft is taken. No bone is harvested. Both 
the femoral and tibial tunnels are anatomically placed in the native footprint of the ACL 78. The graft is 
secured with resorbable RIGIDFIX® Curve Cross Pin System (DePuy Synthes) proximally and, after 
preconditioning and in 30deg of flexion, with a Milagro screws (DePuy Synthes) distally. 
 
IMMEDIATE POSTOPERATIVE CARE 
Following fixation, graft tension and stability are confirmed, ensuring no impingement. The joint is 
thoroughly irrigated, subcutaneous tissues are closed with resorbable sutures, and the skin is sutured 
intracutaneously with nylon. Ropivacaine is administered intra-articular and in the portals for pain 
management. Sterile dressing and cooling bandage are applied. 
 
POSTOPERATIVE PLAN AND REHABILITATION 
{11c, 11d} 
Analgesics are prescribed via the electronic prescription system. Sutures are removed 10–14 days 
postoperatively at the nurse's outpatient clinic, and clinical follow-up with the operating surgeon is 
scheduled at 3–4 months.  
The patient is referred to the rehabilitation program offered as usual care immediately postoperatively. 
The patient is not required to follow usual care but is allowed to seek private alternatives. The 
adherence to rehabilitation is tracked bi-weekly in terms of hours completed supervised and home-
based for descriptive purposes.   
The regional rehabilitation plan guiding usual care in rehabilitation after ACL reconstruction 79 
emphasizes full weight-bearing and unrestricted range of motion from day one, daily mobility 
exercises, and progressive strength and stability training. It includes criteria- and time-based 
milestones, such as cycling at 6 weeks, jogging at 16 weeks, and gradual return to sport-specific 
training after 9–12 months. Supervised sessions are supplemented by home-based training programs. 
Return to sports involving physical contact and cutting maneuvers is not recommended until after 12 
months. 
 
STUDY PERSONAL  
This study is conducted as a single-center study to ensure uniform clinical procedures and 
postoperative care. Orthopedic surgeons from the Arthroscopic Center, Department of Orthopedic 
Surgery, Hvidovre Hospital are affiliated with the project. All participating surgeons have substantial 
experience in anterior cruciate ligament (ACL) reconstruction. In the year leading up to project 
initiation, a comprehensive training program will be implemented for all surgeons to ensure balanced 
use of ST/GR grafts, BPTB grafts, and quadriceps tendon (QS) grafts. This approach is intended to 
ensure equal proficiency across techniques and to minimize the risk of experience-related bias.  

 
 
 
Clinical outcome collection is performed by PI, Per Hölmich (not performing ACL reconstructions in 
the trial) and a project assigned surgeon (not assessing own patients).  Each surgeon performs both 6 
and 12 months follow up on the same patient. This is only deviated from if the risk of missing data due 
to logistics and scheduling occurs. 
 
OUTCOMES 
{12}  
This protocol describes a large clinical trial using a holistic research approach with outcomes 
assessed based on four work packages with assigned outcome measures. The trial time points are 
baseline, 1, 6, 12 and 24 months. In addition, a bi-weekly tracking via SMS was performed (appendix 
4). Follow-up at 12 months was decided as primary time frame as this corresponds to the point in time 
in usual care that the patient is released from clinical follow-up unless adverse effects have occurred 
prolonging the rehabilitation. Follow-up was decided to continue to 24 months, as this is the time 
point classified as medium term in surgical follow-up 80. Additionally, the Hospital policy is to advice 
the patients to refrain from full sports participation until 12 months, making the time from 12 to 24 
months most relevant in terms of the ability to return to sport. A full overview of outcomes is provided 
in table 4. The timepoints of which the outcomes assigned to each outcome is obtained is presented 
in table 5 in participant timeline 
 
WORK PACKAGES 
Trial outcomes have been designed with four main work packages, inspired by domains highlighted in 
the Panther consensus on ACL injury clinical outcomes81 and Panther Symposium ACL Injury Return to 
SportConsensus82. Each work package will provide outcomes to answer different research questions 
and objectives, which will be outlined in detail in the statistical analysis plan.  Relevance and purpose 
of each work package is described below.  
 
WORK PACKAGE 1: PATIENT-REPORTED OUTCOMES 
Patient reported outcomes measures (PROM) are key to capturing the patients’ perception of effect 
and possible persistent impairments following ACL reconstruction. According to the 
recommendations of the Panther statement 81, relevant domains to report using patient-reported 
outcome measures are subjective knee function outcomes, psychological measures, health related 
quality of life (HRQol) and return to sport, which are all covered in work package 1 and will be 
elaborated on below.  
In addition to the recommended domains, a work life outcome measure was added under a 
participation domain along with return to sport. Given the age and activity level of the population, work 
life function, may influence patient satisfaction and perception of function and symptoms to the same 
or larger degree as sports participation.   
Patient Acceptable Symptom State (PASS) which is a dichotomous PROM assessing whether patients 
consider their knee function acceptable (yes/no), was added as a global satisfaction measure 
summing up patient perception across domains reported.   

 
 
 
SUBJECTIVE KNEE FUNCTION 
 
 
 
                                                
International Knee Documentation Committee (IKDC) score at 12 months was selected as primary 
outcome for objective 1 of the trial.  
 
 
 
                                     
IKDC is considered GOLD STANDARD, as a validated patient-reported outcome measure used to 
assess symptoms, function, and sports activity in individuals with various knee conditions, including 
ACL injuries, meniscal injuries, and osteoarthritis83. Scores range from 0 to 100, where higher scores 
indicate better function.  
Knee Numeric-Entity Evaluation Score for Anterior Cruciate Ligament Injuries (KNEES-ACL) is a 
condition-specific PROM designed for individuals with ACL injuries. It consists of seven subscales 
assessing daily activity limitations, psychological burden, symptoms, perceived weakness, instability, 
sports-related behavior, and physical sports participation. Responses are assigned numerical values 
(0–3 or 0–4), with total scores for each subscale ranging from 12 to 24. As all participants are ACL-
reconstructed, a 0.7-point differential item functioning  adjustment is applied to the "perceived 
weakness" subscale for scores in the range of 9–20, and a 1-point reduction is applied to the 
"instability" subscale for patients 6–12 months postoperatively 84,85. 
Donor Site-Related Functional Problems Following ACLR Score is a PROM assessing donor-site 
morbidity following ACL reconstruction with autografts. The questionnaire consists of 16 items, each 
scored on a 0–6 verbal rating scale, where 0 indicates never/not at all and 6 indicates always/totally 
(ref). 
 
PSYCHOLOGICAL MEASURES 
 
 
 
 
                                    
ACL-Return to Sport after Injury (ACL-RSI) is patient-reported PROM assessing psychological 
readiness to return to sport, with scores ranging from 0 to 100, where higher scores indicate greater 
readiness.  
 
Tampa Scale for Kinesiophobia (TSK-11) is a patient-reported PROM assessing fear of movement and 
re-injury, with scores ranging from 11 to 44, where higher scores indicate greater fear of movement. 
 
 
 
 
 
                                     
PARTICIPATION 
 
 
 
 
                                    
Return to sport ability is reported with a PROM assessing pre-injury sport level, return to sport status 
and experienced barriers of return to sport. The questionnaire is modified from a questionnaire 
developed for patient with femoroacetabular impingement-syndrome86,87 based on themes and 
terminology from the return to sport consensus statement82.  
Return to work ability is reported with a PROM assessing the patients’ ability to return to their specific 
work function and workload in terms of pain, sick leave status and an estimation of workability. The 
questions were adapted from the validated WORQ questionnaire88 and the published 
SeniorWorkingLife - push and stay mechanisms for labor market participation among older workers89 
with counseling from the National Research Centre for the Working Environment. 
As an addition, patients report their return to work and return to sport status through biweekly SMS-
track surveys during the first postoperative year with questions adapted from the main questionnaires. 
Participation in rehabilitation (adherence and barriers) is similarly registered through biweekly SMS-
track surveys. 
 

 
 
 
HEALTH RELATED QUALITY OF LIFE 
EQ-5D™ is a generic health-related quality of life (HRQoL) PROM evaluating five domains: mobility, 
self-care, daily activities, pain/discomfort, and anxiety/depression. Each domain is assessed on a 5-
point verbal rating scale, where 0 indicates no problems and 5 indicates extreme problems or inability 
to perform the activity. Permission to uses EQ-5D has been obtained (Registration ID: 74677) 
 
WORK PACKAGE 2: MOVEMENT BIOMECHANICS & NEUROMUSCULAR CONTROL  
The movement biomechanical work package was designed to meet the criteria highlighted in the 
consensus for return to sport to include quality of movement, strength, range of motion, balance, and 
neuromuscular control of the lower extremity and body in the evaluation (KILDE). Muscle strength and 
balance has been investigated in prior RCT’s on graft choice. Neuromuscular control and quality have 
however been overlooked in this randomized context. To this end it has been necessary to classify 
several of these outcomes “explorative” (Table 4).  Domain investigated in WP 2 are neuromuscular 
control, strength, movement quality and performance. 
NEUROMUSCULAR CONTROL 
 
 
 
                                   
Isometric Rate of Torque Development was measured (appendix XX) and is reported as Limb 
Symmetry Index (RTD-LSI). RTD measures the ability to generate torque rapidly during isometric 
contractions (Nm/s), which is a key indicator of neuromuscular function and ACL protection. RTD for 
both injured and non-injured leg is assessed using isometric dynamometry in the biomechanics 
laboratory and expressed as RTD in the injured leg in percentage of the non-injured leg. RTD has been 
selected as primary outcome contrary maximal muscle strength which has been evaluated 
extensively. RTD has been shown to been impaired to a larger degree than maximal strength and is 
emphasized as an important function to evaluated following ACL reconstruction 68,90.  
The primary outcome for objective 2 is the Rate of Torque Development Limb Symmetry Index (RTD-
LSI) at 12 months knee flexion. This was chosen based on the evidence that hamstring activation and 
hamstring function is important to protect the ACL 91, and that young patients with ST/Gr have a larger 
incidence of re-rupture in larger cohort studies92.  RTD-LSI in knee flexion at 12 months was 
prespecified as a secondary outcome solely as this was not included in the power calculation. It is 
considered an outcome crucial to answer objective 2 in full.   
STRENGTH 
 
 
 
 
 
                             
Maximum Voluntary Isometric Contraction Limb Symmetry Index (MVIC-LSI) I performed to evaluate 
maximal quadriceps and hamstring strength (Nm) through standardized isometric dynamometry 
(Metitur, FI) (APPENDIX 2). 
3-D MOVEMENT ANALYSIS  
 
             
 
                
Instrumented 3-D movement analysis was performed to report on the domains: movement quality, 
performance and neuromuscular control. Full protocol is added in appendix 2. Outcome variables 
from the movement analysis are outlined in table 4: 
As emphasized in the panther consensus81,82, variability in test batteries investigating movement 
quality and neuromuscular control remains. The protocol was designed based on test previously 
reported in the literature with a variation of one-leg jumps for comparison between the healthy and 
reconstructed leg for LSI quantification. The jump tasks were selected to include simple jumps with 
vertical and horizontal propulsion and landings as well as combination jumps with transitions from 
landing to propulsion in both vertical and horizontal direction93. The following jump tests are assessed: 

 
 
 
Single-leg horizontal jump, Single-leg vertical jump, single-leg horizontal to vertical jump, single-leg 90 
degrees rotation jump, counter-movement jump, single-leg triple-jump for distance, cross-over triple 
jump for distance and 6 timed one-leg jump. 
All jump tasks are assessed using 3D motion capture analysis (Vicon motion systems, Oxford, UK) with 
the clinical gait-model 2.3 lower limb marker set for reporting movement kinematics. Simultaneous 
capture of ground reaction force is captured on AMTI force plates (OR6-7, Watertown, MA, USA) to 
report movement kinetics. Finally, synchronized surface electromyography measurements were 
collected to report neuromuscular control of thigh muscles and hamstrings (appendix 2). Performance 
in jump tasks (height, distance) were calculated from 3-D motion capture and force platform data 
(table 4).  
 
WORK PACKAGE 3: CLINICAL ASSESSMENT and MEDICAL IMAGING 
WP 3 was designed based on usual care and recommendations from the panther consensus on 
clinical assessment. Clinical assessments and medical imaging are key for determining the clinical 
efficacy and effectiveness of each treatment, but WP3 is similarly designed to identify modifiable and 
non-modifiable predictors of good and poor outcomes in WP 1 and WP 2. Domains reported in WP3 
are objective knee function, adverse events, perioperative outcomes, Muscle morphology & 
anatomical predispositions. Detailed protocols for medical imaging are added in appendix 3. 
OBJECTIVE KNEE FUNCTION 
 
 
 
                                                  
Clinical knee stability assessments are performed by an experienced orthopedic surgeon blinded to 
allocation reporting:  
 
 
 
 
 
     
The Rolimeter test measures anteroposterior tibial translation (mm) to assess ACL stability; The pivot 
shift test evaluates rotational knee stability, graded 0 to 3 (0 = no shift, 3 = severe shift); Passive Range 
of Motion (RoM) in knee extension and knee flexion in degrees; The dial Test in 30 and 90 degrees of 
knee flexion to evaluate posterolateral rotatory instability (PLRI); Medial and lateral laxity to evaluate 
the integrity of collateral ligaments and the joint effusion test to evaluate presence of inflammation. 
PERIOPERATIVE DETAILS & ADVERSE EVENTS 
Prespecified perioperative details are extracted from medical records: including surgeon, concomitant 
injuries, meniscal tears below exclusion criteria level and treatment, graft length and diameter94, 
tunnel placement, and surgical duration.  
 
Prespecified adverse events are recorded via medical records, including infection, arthrofibrosis, 
meniscal injury, graft rupture, and revision surgery. 
 
Postoperative X-rays are reviewed to assess tunnel placement. 
 
MUSCLE MORPHOLOGY & ANATOMICAL PREDISPOSITIONS.   
 
                         
Magnetic resonance imaging (MRI) scans are performed on the thigh muscles of both legs to report 
symmetry indices of muscle length of semitendinosus95 and cross-sectional area of biceps femoris, 
semitendinosus, gracilis, vastus medialis, vastus medialis and rectus femoris96.  
Postoperative X-rays are reviewed to report lateral tibial slope of the reconstructed knee97. 
 

 
 
 
 
 
Instrument / Test 
Domain 
Outcome Variables / 
Scores 
Assessment & Validity 
Work Package 1: Patient-reported function 
Primary outcome 
WP 1  
International Knee 
Documentation 
Committee  
(IKDC) 
Subjective knee 
function 
Total IKDC score (0–100)  
Validated PROM.  
Gold standard for follow up after 
ACL reconstruction83. 
Secondary outcomes 
WP 1 
Knee Numeric-Entity 
Evaluation Score for 
Anterior Cruciate 
Ligament Injuries 
(KNEES acl) 
Subjective knee 
function  
 
7 subscales with total 
score ranging from 12-24.   
Condition-specific validated 
PROM84,98.  
WP 1 
EQ-5D 
Health-related quality      
of life 
Domain scores (1–5)  
Validated HRQoL PROM99 
WP 1 
TSK-11 
Psychologic effects 
Total score (11–44) 
Validated fear-of-movement 
PROM100 
WP 1 
ACL-RSI 
Psychologic effects 
ACL-RSI score (0–100) 
Validated psychological readiness 
scale101 
WP 1 
PASS 
Global satisfaction 
dichotomous outcome 
(yes/no)  
Validated PROM on acceptable knee 
function102. 
WP 1 
Return to Sport 
Participation 
Self-reported ability to 
return to participation and 
performance in pre injury 
sport (primary and 
secondary), and level 
(Elite, competitive, 
leisure). 
 
Self-reported barriers             
(Pain, donor-site pain, 
laxity, swelling)  
Modified patient reported outcome 
measure based on a return to sport 
consensus statement from 201586,87 
  
 
WP 1 
Donor Site-Related 
Functional Problems 
Following ACLR Score 
Subjective knee 
function 
16 items, each scored on 
a  0–6 rating scale.                    
(0=never/not at all) 
Validated donor-site morbidity 
PROM103  
WP 1  
Return to Work 
Participation 
Self-reported work-ability 
Knee related sick leave  
Modified patient reported outcome 
measure with questions adapted 
from validated surveys 88,89.   
Explorative outcomes 
WP 1 
SMS-based tracking 
Rehabilitation 
compliance 
Adherence to 
rehabilitation (time)  
Pain interference with 
rehabilitation (yes/no) 
Knee related medical 
assistance beyond 
standard follow-up 
(yes/no) 
Custom patient reported registration 
Subjective knee 
function 
Knee function (numeric 
scale Sports participation 
ability (numeric scale) 
Workability (numeric 
scale) 
pain level (numeric scale) 
Pain scores and numeric scales 
adapted from IKDC  

 
 
 
Work Package 2: Movement Biomechanics & neuromuscular control  
Primary outcome 
WP2 
 
Isometric Rate of Torque 
Development                          
– knee extension 
Neuromuscular 
control 
Limb symmetry of-Rate of 
Torque Development in 
knee flexion (%) 
Standardized dynamometry, 
validated LSI method104 
Secondary outcomes 
WP 2
 
 
Isometric Rate of Torque 
Development                      
– knee flexion 
Neuromuscular 
control 
Limb symmetry of-Rate of 
Torque Development in 
knee extension (%) 
Standardized dynamometry, 
validated LSI method104 
WP 2 
Maximal Voluntary 
Isometric Contraction  
Strength 
LSI-MVIC (%) 
Standardized dynamometry 
Explorative outcomes 
WP 2 
One-legged jump tasks 
(Appendix 2)  
 
Movement quality 
3D kinematics: 
LSI in landing angles of 
knee, hip and ankle  
RoM during landings and 
propulsion 
Validated instrumented method for 
movement analysis and load 
evaluation31,91 
WP 2  
Movement quality 
3D kinetics: 
LSI in joint moments, 
power and work during 
landings and propulsion 
WP 2 
Performance 
LSI on jump height, 
distance, time and 
reactive strength index 
Validated return to sport metrics 105 
WP 2 
Neuromuscular 
control 
Surface 
electromyography: 
Magnitude of EMG 
response (% of max) 
during landing and 
propulsion   
Timing of EMG response 
before and during 
landing.   
Validated injury risk evaluation91 
Work Package 3: Clinical assessment and Medical imaging 
Secondary outcomes 
WP3 
Clinical knee exam 
Objective knee 
function 
Rolimeter (mm) 
Pivot Shift (0-3 grading) 
Blinded orthopedic testing with 
standardized tools32,52 
Explorative outcomes 
WP3 
Clinical knee exam 
Objective knee 
function 
Dial Test (degrees), Range 
of Motion (degrees),                 
medial and lateral laxity 
(yes/no),                                        
joint effusion (yes/no).  
Standard postoperative clinical 
examination of the knee joint.  
WP3 
Patient medical file  
Adverse event 
Re-rupture, revision 
surgery, medical 
complications 
Prespecified log 
WP3  
Patient medical file 
Perioperative 
information 
Graft size, adverse 
events, knife time. 
Prespecified log 
WP3  
Magnetic Resonance 
Imaging  
(MRI) 
Muscle morphology 
Muscle length (mm),               
Cross Sectional Area 
(mm²) 
Blinded MRI analysis, validated 
anatomical landmarks and methods  
WP3 
X-ray imaging 
Perioperative 
information 
tunnel placement 
Blinded assessment, Calibrated 
radiographic imaging 
WP3 
Anatomical 
predisposition 
Lateral tibial slope 

 
 
 
Descriptive features of populations sample 
Exploratory and descriptive outcomes 
 
Inclusion interview and 
patient file logging 
 
Patient features and 
anthropometrics 
Age, Height, Weight, 
Biological sex 
Custom patient reported registration 
 
 
Preinjury participation  
Primary and secondary 
sport, hours and level of 
participation. 
Occupational level 
 
Injury information 
Time from injury to 
surgery, Injury situation 
(mechanism), Preferred 
leg.  
Table 4 – Overview of work packages and all corresponding outcomes and instruments in the GRASE ACL trial.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
DATA COLLECTION AND MANAGEMENT 
 
PARTICIPANT TIMELINE  
{13} 
Participants will be followed from preoperative assessment to 24 months post-surgery (Table 5).                
Assessments include patient-reported outcomes (PROMs), clinical evaluations, biomechanical 
testing, and imaging, scheduled to optimize participant convenience and minimize burden. Follow-
ups are scheduled for 1, 6, 12 and 24 postoperatively. 
 
Enrollment 
Surgery 
Follow-ups 
Timepoint (mo.) 
-1 
0 
1 
6 
12 
24 
ENROLLMENT 
Eligibility screen 
x 
 
 
 
 
 
Informed consent 
x 
 
 
 
 
 
Baseline demographics & descriptive 
features of population sample 
x 
 
 
 
 
 
INTERVENTION 
ACL reconstruction surgery 
 
x 
 
 
 
 
Surgical details  
 
x 
 
 
 
 
Allocation 
 
x 
 
 
 
 
ASSESSMENTS 
WP 1 Patient-reported 
IKDC  
x 
 
x 
x 
x 
x 
KNEES-ACL 
x 
 
x 
x 
x 
x 
Donor Site-Related Functional Problems 
 
 
 
x 
x 
x 
PASS 
 
 
 
x 
x 
x 
EQ-5D  
x 
 
x 
x 
x 
x 
ACL-RSI 
 
 
 
x 
x 
x 
TSK-11 
x 
 
x 
x 
x 
x 
Return to Sport questionnaire 
 
 
 
x 
x 
x 
Return to Work questionnaire 
 
 
x 
x 
x 
x 
Bi-weekly sms-based tracking   
x 
 
WP 2  Biomechanical 
RTD-LSI 
 
 
 
x 
x 
 
MVIC-LSI 
 
 
 
x 
x 
 
Jump performance  
 
 
 
x 
x 
 
3D kinematics/kinetics 
 
 
 
x 
x 
 
Muscle activity (EMG)  
 
 
 
x 
x 
 
WP 3  Clinical 
Objective Knee stability  
x 
 
 
x 
x 
 
Passive RoM  
x 
 
 
x 
x 
 
Adverse events (from records) 
 
 
 
 
 
x 
WP 4  Medical Imaging  
MRI of thigh muscle 
 
 
 
x 
 
 
Postoperative X-rays  
 
 
 
x 
 
 
Table 5 – Time points of assessment and participant timeline from enrollment until 24 months post-surgery.  
 
 

 
 
 
PLANS FOR ASSESSMENT AND COLLECTION OF OUTCOMES  
{18a} 
Patient-reported outcomes (PROMs) will be collected electronically via e-mail link in REDCap 
(Research Electronic Data Capture), a secure, web-based platform hosted by Region Hovedstaden. 
REDCap contains options for valid values, range checks, data validation, branching, scheduling, and 
stop-rules to increase data quality. Questionnaires administered are described in WP1 in the 
outcomes section.  
Clinical assessments, including knee stability tests, will be performed by blinded clinicians at 
standardized follow-up time points, and registered in the patient medical file (EPIC Hyperspace®) 
(appendix 1). Prespecified clinical and surgical details will be extracted from medical records, and 
adverse events will be documented throughout the study in secured folders with logged access.   
SMS-based surveys (SurveyXact) will be used for biweekly data collection on pain, rehabilitation 
compliance, healthcare utilization, return to sport, and return to work during the first postoperative 
year. 
To ensure consistency and data integrity, all assessors will undergo standardized training, and detailed 
data collection protocols will be available upon request. 
Biomechanical outcomes will be assessed using isometric dynamometry, 3D motion capture (Vicon 
Motion Systems, Oxford, UK)), and surface electromyography (EMG) in the Motion Analysis laboratory. 
The full laboratory protocol is attached in appendix 2.  
 
Data on Non-Participants 
Non-sensitive baseline data and reasons for opting out will be recorded anonymously for eligible 
individuals who decline to participate. This information will be utilized in analyses to evaluate 
population characteristics and identify potential selection biases. 
 
Managing Allocation Deviations 
It is possible, though predicted to be very rare, that some participants deviate from their assigned graft 
due to intraoperative complications. In these instances, data collection will continue as planned to 
facilitate intention-to-treat analyses. 
 
Managing Protocol Deviations 
Participants will adhere to standardized postoperative care, including follow-up with their surgeon and 
receive physiotherapy according to Danish guidelines, with additional care provided as needed. Any 
adverse effects, additional treatments, or interventions will be closely tracked and documented to 
assess their impact on study outcomes. 
 
 

 
 
 
STRATEGIES FOR ENSURING FOLLOW-UP COMPLIANCE 
{18b} 
Adherence to intervention protocols and follow-up assessments will be promoted and monitored 
through multiple strategies to maximize participant retention.  
We will continue data collection irrespective of adherence to rehabilitation and follow-ups. In cases of 
re-injury a clinical evaluation of safety determines if the biomechanical protocol is performed.                      
Data collection will only discontinue if participants explicitly wish to withdraw from the study and not 
attend further visits. In such cases, we will offer participants the option to only complete electronic 
patient-reported questionnaires and/or partial clinical and biomechanical follow-up with focus on 
obtaining primary outcomes. However, every reasonable effort will be made to retain all participants 
and collect all outcomes for every patient enrolled in the study. 
Survey participation will be actively tracked, with reminders sent via email, text messages, and phone 
calls to non-responders. 
• 
Biweekly SMS Surveys: If a participant does not complete an SMS survey, a reminder will be 
sent 2 days later. Data collection is permitted within 1 week before the response is considered 
missing. 
• 
1-Month Survey: Sent 4 days before follow-up time point. Participants who do not complete 
the survey will receive reminders every 4 days, up to three times. If still unanswered, a phone 
call will be made. A 14-day delay is permitted before the data point is considered missing. 
• 
Hospital Follow-Up Visits (6 and 12 months): Participants will receive a confirmation text 
message 1 month and 2 days before their scheduled visit. Scheduling is flexible, and data 
collection is permitted within a 30-day window before or after the follow-up time point. 
• 
6- and 12-Month Surveys: Sent 21 days before the follow-up time point. If participants have not 
completed their surveys before the hospital visit, they will be asked to complete them on an 
iPad during their visit. A 30-day delay is permitted. 
• 
24-Month Survey: Sent 30 days before the follow-up time point. Participants who do not 
complete the survey will receive reminders every 5 days, up to three times. If still unanswered, 
a phone call will be made. A 60-day delay is permitted. 
• 
MRI Scan at 12 months: The scan can be scheduled within a 30-day window before or after the 
designated time point. 
 
DATA MANAGEMENT  
{19} 
The study directors will manage and curate data in collaboration with the blinded statistician. 
REDCap users (study personnel) will have access to all instruments and data within the REDCap 
project to maintain blinding to group allocation, outcomes, and contents of interventions. Digital 
consent forms are stored in REDCap. Other hardcopy data will be stored in locked steel cabinets in a 
locked room and will be stored for 3 years after completion of the long-term follow-up of the study. 
Data from biomechanical analysis holds video material with the consent of each participant. Data 
from these analyses is processed in NEXUS versions XXX (VICON systems), but stored in logged, 
secure drives only accessible by study personnel.  

 
 
 
 
DATA PROTECTION & CONFIDENTIALITY  
{27,33} 
This study complies with the General Data Protection Regulation (GDPR) and Danish Data Protection 
Law. Region Hovedstaden is the data controller responsible for processing personal data, with 
oversight from the Danish Data Protection Agency (Jr. no. VD-2018-524).  
All personal and health data will be securely stored within Region Hovedstaden’s IT infra-structure, 
with strict confidentiality measures in place. Personal and health data are stored in a secure, 
password-protected database with regular backups, and only authorized research personnel will have 
access to de-identified study data. Identifiable information will be re-moved or encrypted to ensure 
privacy. Study data will be retained for 10 years in accordance with regulatory guidelines. External data 
processors, such as SurveyXact and University College Copenhagen, are involved in handling pseudo-
anonymized data for project-related analysis.  
Participants have the right to access their personal data, request corrections or deletions (subject to 
legal research exemptions) and withdraw consent at any time without affecting their medical care. If a 
participant withdraws consent, no new data will be collected, but previously gathered data will be 
retained for research integrity. 
 
STATISTICAL ANALYSIS PLAN 
Final version of the statistical plan has been specified per 30-06-25, and follows the pre-SPEC 
framework of statistical analysis strategies in clinical trials 106. 
Demographic parameters will be presented for each graft group. Continuous variables will be 
summarized as mean with standard deviation (SD) or median with interquartile range (IQR), depending 
on the distribution. Categorical variables will be presented as frequencies and percentages.  
Analysis will follow an intention-to-treat (ITT) approach. To check the robustness of the primary 
intention-to-treat analysis, per protocol analysis on primary outcomes will be performed.  
Statistical models specified below will be set up by a statistician in R with a dummy allocation to 
ensure full blinding in the statistical analysis. R codes will be available upon request.  
 
STATISTICAL MODELS and HANDLING OF MISSING DATA 
{20c} 
For continuous data, a t-test will be used. Assumptions of normality will be evaluated using QQ-plots 
and histograms. If variances are not homogeneous, Welch’s t-test will be applied. For non-normally 
distributed data, the Mann-Whitney U-test will be employed. 
Adjusted analysis will be done by expanding t-test using mixed effect linear regression models.  

 
 
 
To not introduce unnecessary bias in regression models, possible covariates will however only be 
included if doing so changes the primary estimate meaningfully, as we expect equal distribution of 
these pre-specified covariates given the sample size and randomization process. The linear models 
will be evaluated for linearity, multicollinearity, homogeneity of variance, distortion of outliers, 
homoskedasticity, correlation of variables, distribution of residuals using histograms. If these model 
assumptions are not met nonparametric bootstrap estimation and tests will be used instead. 
Missing data will be imputed by multiple imputation, with imputation models based on available 
variables believed to be predictive of the missing measures. All available variables will be included in 
the imputation models, unless a specific reason is given for exclusion. 
 
STATISTICAL METHODS FOR PRIMARY AND SECONDARY OUTCOMES  
{20a, 20b} 
PRIMARY OBJECTIVE 1 
Three distinct hypotheses on patient-reported effect of graft choice will be tested for change in the 
IKDC score 12 months after surgery: 
QT (Group A) is non-inferior to BPTB (Group B). 
QT (Group A) is non-inferior to ST/Gr (Group C). 
BPTB (Group B) is non-inferior to ST/Gr (Group C). 
 
Each hypothesis will be tested using a non-inferiority two-sample t-test, with non-inferiority margin of 
7 points, which is considered a clinically relevant difference based on prior studies 76,107. As the three 
hypotheses are independent, no adjustment for multiple comparisons will be applied to the p-values.  
To provide additional insight into the effects and safety of graft types, secondary outcomes will be 
analyzed as follows:  
• 
KNEES-ACL score at 12 months will be assessed using a non-inferiority approach, with a non-
inferiority margin of 8 points. As no established threshold exists in the literature, this margin is 
chosen conservatively based on expert consensus and comparisons with other knee-specific 
PROMs 98.  
• 
Donor-site related functional problems, PASS, EQ-5D, rolimeter measurements and pivot shift 
at 6 and 12 months will be analyzed using a superiority approach with three-way comparisons. 
 
Adjusted analysis will be done by expanding t-test using linear regression models. Confounding effects 
will be evaluated by including and removing the following covariates in statistical model. 
Possible confounders include: 
• 
Patient-related factors: sex, BMI, age, physical activity prior to injury, time from injury to 
surgery, and tibial slope, and surgeon. 
• 
Concomitant injuries: Meniscal and chondral injuries and treatment. 
• 
Knee function prior to surgery: Range of motion (ROM), Rolimeter, pivot shift, medial and 
lateral laxity tests, and dial test results. 
• 
 

 
 
 
To explore mechanisms underlying treatment effects, the following variables will be reported: 
• 
Surgical details: Graft size and tunnel placement. 
• 
Healthcare Utilization: Number of additional physician consultations during the first 
postoperative year, tracked biweekly via SMS surveys (SurveyXact). 
• 
Follow-up knee examination at 6 and 12 months: Passive ROM, medial and lateral laxity, and 
dial test results. 
• 
Pain Assessment: Patient-reported pain scores, using the same two pain-related questions as 
in the IKDC questionnaire, collected biweekly during the first postoperative year via SMS 
surveys (SurveyXact). 
• 
Complications and adverse events: Including infections, arthrofibrosis, meniscal lesions, graft 
failure, and other relevant events, recorded via medical records. 
 
 
PRIMARY OBJECTIVE 2 
A superiority approach will be applied to assess differences between groups on RTD-LSI in knee flexion 
at 12 months postoperatively. A composite hypothesis of differences between groups will be tested, 
consisting of two pairwise comparisons: 
• 
QT (Group A) versus ST/Gr (Group C). 
• 
BPTB (Group B) versus ST/Gr (Group C). 
 
For RTD-LSI in both knee flexion and knee extension a superiority approach will be applied to assess 
differences between groups. A composite hypothesis of differences between groups will be tested, 
consisting of three pairwise comparisons: 
• 
QT (Group A) versus BPTB (Group B). 
• 
QT (Group A) versus ST/Gr (Group C). 
• 
BPTB (Group B) versus ST/Gr (Group C). 
 
Each pairwise comparison will be analyzed using a two-sample t-test. To control for the potential 
inflation of type I error due to multiple testing, the max-t/min-p test for multiple comparisons will be 
applied108. 
The secondary outcome MVIC-LSI in knee flexion and knee extension will be analyzed using the same 
method. 
Mixed effect linear regression models will be used to analyze the effect of RTD-LSI on 1: Kinetic and 
kinematic outcomes during one-leg landing and propulsion, 2: Performance in isolated horizontal, 
vertical and horizontal to vertical jumps and 3: Subjective knee function in terms of IKDC and KNEES at 
12 months.  
Adjusted analysis will be done by expanding t-test using linear regression models. Confounding effects 
will be evaluated by including and removing the following covariates in statistical models. 
 
 

 
 
 
Possible confounders include: 
• 
Patient-related factors: sex, BMI, age, physical activity prior to injury, injury mechanism, and 
time from injury to surgery. 
• 
Concomitant injuries: Meniscal and chondral injuries and treatment. 
• 
Pain domain of KNEES-ACL at 12 months. 
 
To explore mechanisms underlying treatment effects, the following variables will be reported: 
• 
Knee function prior to surgery: Range of motion (ROM), Rolimeter, pivot shift, medial and 
lateral laxity tests. 
• 
Donor Site-Related Functional Problems Following ACLR Score at 12 months. 
• 
Complications and adverse events recorded via medical records. 
 
METHODS FOR ADDITIONAL ANALYSES  
Additional analyses and trial reports are pipelined for the full trial answering the additional objectives 
outlined previously.  
Additional analyses will investigate differences between the three graft choices according to a 
superiority framework, and adhere to the same missing data handling, assumption testing and control 
for the potential inflation of type I error as specified above. 
INTERIM ANALYSES  
{21b} 
No interim analyses or stopping rules are planned to preserve statistical power. The three treatment 
options employed can be classified as usual care, thus safety concerns are very low. 
 
RISK OF BIAS 
A risk of bias analysis was performed prior to final inclusion according to the RoB 2 framework 2. Bias 
arising from the randomization process, bias due to deviations from intended interventions were 
reported as low risk domains as randomization was very controlled and performed simultaneous with 
completed interventions.    
Bias in measurement of outcomes and bias in selection of reported result were reported as low risk 
domains as all outcomes were selected in accordance with recommendations in clinical and 
scientific consensus groups, and outcome reporting and statistical analyses plans were pre-specified.  
Bias due to missing outcome data was reported with some concerns of bias. To meet this concern, the 
patients’ reason for possible dropout our missing an assessment was registered. In addition, several 
strategies for retention of participants and adherence to trial outcome assessments were designed. 
 
 

 
 
 
PLANS TO GIVE ACCESS TO THE FULL PROTOCOL, PARTICIPANT LEVEL-DATA AND 
STATISTICAL CODE  
{31c} 
Full methodological protocols for biomechanical assessment and medical imaging are attached to 
this current protocol.  
Statistical code and participant-level dataset will be available upon demand, to the extent that it does 
not compromise Danish Data Protection Law. 
 
ETHICS AND DISSIMENATION 
 
RESEARCH ETHICS APPROVAL 
This trial will be conducted in compliance with the principles of Good Clinical Practice (GCP) as set 
out by the International Conference on Harmonization (ICH) and the Declaration of Helsinki. This 
study has received approval from the Scientific Ethics Committee for the Capital Region (Journal-no.: 
H-19001194). Any significant protocol amendments will require re-approval by the relevant ethics 
committees. 
RISK AND SAFETY CONSIDERATIONS 
Biomechanical evaluations may cause temporary muscle soreness or fatigue, particularly after 
strength or dynamic movement tests. Additionally, there is a slight risk of strain during physical tasks, 
but participants will be closely supervised to reduce this risk. To reduce risks, it was attempted to plan 
the clinical examination prior to biomechanical examination to ensure integrity of the new ACL.  For 
patients with low function, the demanding tasks combining landing and propulsion were avoided.  
MRI scans, while non-invasive, may lead to discomfort due to the enclosed space, noise, and duration 
of the procedure. A postoperative X-ray will be performed, involving minimal radiation exposure. 
Comprehensive safety protocols are in place to monitor and address any potential adverse effects 
throughout the study. 
HARMS 
{22} 
Adverse events and unintended effects will be closely monitored throughout the trial by the 
designated non-blinded personnel. Any serious adverse events will be reviewed by clinical personnel 
and promptly reported to the relevant ethics committees. Participants who experience adverse effects 
related to the trial interventions will receive appropriate medical care according to local clinical 
guidelines. Participants are encouraged to report any health issues during the study, and they will be 
immediately informed if any new side effects or risks are identified during the trial. 
 

 
 
 
COMPENSATION TO PATIENTS 
No participants will receive reimbursement for their travel expenses related to participation in the 
study, nor will participants be offered compensation of any kind. During treatment at Hvidovre 
Hospital, the participants will be covered under the Danish Patient Compensation Act (LBK no 995 of 
14/06/2018, chapter 3 §19) (In Danish: Patienterstatningen), which is a scheme that deals with 
compensation claims of patients treated in the public health system in Denmark who has sustained 
an unintended or unexpected injury or harm.  
 
DECLARATION OF INTERESTS 
The principal investigators and collaborators involved in this trial declare no financial or other conflicts 
of interest that could potentially influence the study outcomes. Any future competing interests will be 
disclosed in relevant publications and reports. 
 
DISSEMINATION PLANS  
{31a} 
The results of the trial will be shared through peer-reviewed journal publications, conference 
presentations, and updates to ClinicalTrials.gov. Key findings will also be communicated directly to 
participants who have expressed interest in receiving study results, as indicated when they signed the 
consent form, as well as to relevant healthcare professionals. There are no publication restrictions, 
allowing for full transparency and broad dissemination of the findings. Primary trial reports are listed 
below.  
 
PRIMARY TRIAL REPORTS 
• 
Optimizing GRAft SElection in ACL reconstruction (GRASE ACL): effect of graft choice on 
patient reported knee function and knee stability.  
Reporting the primary outcome corresponding to objective 1 – the patient centered perspective 
supported by secondary outcomes previously outlined in the statistical plan.  
 
• 
Optimizing GRAft SElection in ACL reconstruction (GRASE ACL): effect of graft choice on rate of 
torque development and the consequences to dynamic control of the knee.   
Reporting the primary outcome corresponding to objective 2 – the biomechanical perspective 
supported by secondary outcomes and analyses previously outlined in the statistical plan. 
 
ADDITIONAL TRIAL REPORTS 
Further publications based on data from the trial will be conducted and should adhere to the pre-
specified main statistical plans outlined for in METHODS for additional analyses with full transparency 
on outcome status presented in this current protocol on disseminated outcomes. 
 

 
 
 
TENTATIVE ADDITIONAL DISSEMENATIONS ON THE PRIMARY TIMEPOINT (12mos) 
• 
Influence of graft selection on return-to-work ability following ACL reconstruction.  
The primary objective is to investigate the effect of graft selection on workability reported in the 
workability questionnaire and additionally biweekly SMS-tracking.  
The secondary objective is to evaluate probable clinical and patient-reported barriers and facilitating 
factors of work ability will be analyzed.  
  
• 
Influence of graft selection on readiness for safe return to sport 12 months after ACL 
reconstruction.  
The primary objective is to investigate the effect of graft selection on the physical readiness to return 
to sport evaluated with a return to sport battery evaluating performance in return to sport one-leg jump 
tasks and LSI-MVC in quadriceps.  
Barriers and facilitating factors to physical readiness from neuromuscular, clinical and psychological 
outcomes to return to sport 12 months after reconstruction will be analyzed 
 
Secondary objective is to evaluate the psychological and biomechanical readiness for safe return to 
sport. This will be analyzed as the effect of graft selection on known kinetic, kinematic and EMG 
predictors for re-rupture, as well as psychological readiness measured as the ACL-RSI and TSK-11.  
   
AUTHORS’ CONTRIBUTION 
{31b} 
Authorship will be determined based on the International Committee of Medical Journal Editors 
(ICMJE) guidelines. All plans for additional dissemination of trial results must be presented and 
reviewed by the scientific group to avoid bias in data selection and slicing of data. No professional 
writers will be employed in preparing the study's publications. 
 
COMPETING INTERESTS   
 
 
 
                                   
{28}  
Some of the authors have previously published in this area and have designed the experimental 
intervention being tested and are therefore prone to self-citation incentives and confirmation bias. 
Thomas Kallemose is paid for statistical consultation and performing blinded analyses. There are no 
other conflicts of interest to declare. 
 
 
 
 
 
 

 
 
 
OVERSIGHT AND MONITORING 
 
SCIENTIFIC TRIAL STEERING COMMITTEE AND DATA MONITORING COMMITTEE  
{5c, 5d, 21a} 
The Sports Orthopedic Research Center – Copenhagen (SORC-C), specifically PhD-fellows Merete 
Brink Speedtsberg and Cecilie Køllner Olsen and Professor Per Hölmich (Main Supervisor and Medical 
Advisor) and Professor Mette Zebis (Co-supervisor) has initiated and will manage the trial.  
 
Along with Jesper Bencke, they also form the steering- and writing committee, which will oversee the 
trial and decide on authorships and assume stewardship of the data for publications from the two 
phd’s. Further publications and post hoc use of trial data must be approved by Professor Per Hölmich 
(Main Supervisor and Medical Advisor) and Professor Mette Zebis (Co-supervisor). No specific data 
monitoring committee is convened. 
 
Frequency and plans for auditing trial conduct  
 
 
 
     
{23}  
No trial audit is planned.  
 
Plans for communicating important protocol amendments to relevant parties  
     
{25}  
Amendments to the trial will be reported to the review board (Regional Committees on Health 
Research Ethics for The Capitol Region), and the amendments will be reported with justifications in 
the main report.  
All protocol amendments must be approved by the trial scientific committee and when affecting 
statistical and data management aspects amendments Statistician Thomas Kallemose must be 
consulted.   
 
 
 
 
 
 
 
 
 

 
 
 
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Appendix 1 – Clinical knee examination 
Clinical knee examination 
6 months  
  
12 months  
  
 
Has the patients scars been covered?  
Yes  
  
No  
  
 
Reconstructed knee 
Left  
  
Right  
  
 
 
Medical pain relief within the last 24 hours 
Yes  
  
No  
  
 
  
 
Objective measures 
Left 
Right 
Notes 
Pivotshift 
Grade 0 (equal/absence) 
Grade 1 (+glide) 
Grade 2 (++clunk) 
Grade 3 (+++gross) 
 
 
 
Rolimeter (mm) 
 
 
 
Dialtest (30/90) 
 
Grade 0 (0-5 degrees) 
Grade 1 (6-10 degrees) 
Grade 2 (11-19 degrees) 
Grade 3 (≥20 degrees) 
/ 
/ 
 
Knee effusion (yes/no) 
 
 
 
RoM (EXT/FLEX) 
/ 
/ 
 
 
 

 
 
 
Appendix 2 – Biomechanical Protocol 
 
Preparations BEFORE the participant arrives: 
Lab: 
a. Print the test form – Fill in possible information (12 months – transfer Metitur settings) 
b. Check participant’s status for cutting sport at 12-month test 
c. Draw lots for right/left (dice – even = right, odd = left) 
d. Prepare for EMG: electrodes + alcohol wipes + skin scraper 
e. Prepare GRASE markers 
f. Prepare the test track 
g. Prepare for strength measurements: handheld dynamometer, strap, and suction cup for the floor 
 
Metitur 
Calibration of the Metitur is done once a month – see calibration protocol 
Plug in the chair and computer and connect USB from chair to computer 
Switch on at the back of the chair 
Adjust the chair (at 12 months) 
 
Creating a participant 
a. Open the program – Good Strength (check connection) 
b. Select Project: GRASE_HOVEDPROJEKT 
c. Select examiner 
d. Select Channel: Knee 
e. Create/Select participant under system data 
i. S.I.C: ID_GRASE 
ii. First name: ID 
iii. Last name: GRASE 
 

 
 
 
Vicon 
Camera Calibration (Note: check 100Hz) (Mask Cameras; Calibrate; Set Volume Origin etc.) 
Zero-Level Force Plates 
Only keep the EMG receiver turned on when EMG is being recorded. 
 
Creating a participant 
a. Open VICON → research DB – GRASE ACL 
b. Create new subject folder – Participant ID 
c. Create new session in subject folder: Session name “6 months / 12 months” 
d. Create new subject from Labeling Skeleton  
i. Model: GRASE.marts23.TEST2 
 
 

 
 
 
Procedure – Preparation WITH the participant 
Welcome + brief introduction to the program 
 
Anthropometry measurements 
a. Height – (with shoes – ideally same shoes at 6 and 12 months) 
b. Weight – (with shoes) 
c. Inter-ASIS distance (from ASIS to ASIS) 
d. Leg length (ASIS to medial malleolus) 
e. Knee width (lateral to medial epicondyle of the femur at 30° knee flexion) 
f. Ankle width (lateral to medial malleolus) 
g. Thigh circumference 10 cm above the upper edge of the patella 
h. Lever arm: 
i. Mark a line 7 cm proximal to the lateral malleolus 
ii. Measure lever arm (7 cm proximal to the lateral malleolus to the lateral epicondyle of the femur). For 
tall participants, measure a shorter lever arm for use in the Metitur for the few participants whose lever 
arm is longer than 39.5 cm. 
 
Fill out the test form + anthropometric measures in “subject” in Vicon. 
 
EMG placement – Quadriceps 
a. Palpate the muscle belly of VL, RF, and VM to find the most prominent point. 
b. Mark with surgical marker, scrape, and clean with alcohol. 
c. Place EMG electrodes in the following order: 
EMG channel Muscle 
1 
Left VL 
2 
Left RF 
3 
Left VM 
5 
Right VL 
6 
Right RF 
7 
Right VM 

 
 
 
 
Adjust Metitur chair   
See Metitur adjustment protocol 
At the computer: Enter chair settings into the test form + any EMG changes 
 
Standardized Warm-Up  
 
 
 
 
 
TEST PROCEDURE 
RTD + MVC + EMG MVC Quadriceps 
Performed in the following order: 
RTD extension – RTD flexion 
MVC extension + EMG – MVC flexion 
 
REPEATED for left and right sides – side determined by random draw 
 
At the computer – note in test sheet if there are errors in a trial + prepare sock for EMG 
Measure 1× leg length from the center of platform 1 for the jump test 
 
Rate of Force Development (RTD) 
Select Muscle Group: Knee Extension/Flexion Right/Left 60° 
 
A. Test trials without recording 
 
INSTRUCTION: 
Fast and powerful/strong extension or flexion 
Hold for 1–2 sec – do NOT hold until MVC 
NO countermovement 

 
 
 
 
B. Test trial with recording (up to 3 if necessary) 
Measurement → New measurement 
Measurement type: RFD 1 trial 
 
INSTRUCTION: 
Fast and powerful/strong extension or flexion 
Hold for 1–2 sec – do NOT hold until MVC 
NO countermovement 
               
Start test → Zero level 
Countdown 3-2-1 (delayed from the screen) 
Visual error correction and repeat if needed 
 
 
C. RTD measurement – 6× 1–2 sec with 30 sec pause 
 
At the computer: VICON TRIALTYPE: “EMG_MVC” 
Prepare Vicon filename: “RFD_QUAD_inj01” or “RFD_QUAD_heal01” 
Start recording on count “1” 
Mark as “good left” or “good right” 
 
INSTRUCTION: 
Fast and powerful/strong extension or flexion 
Hold for 1–2 sec – do NOT hold until MVC 
NO countermovement 
Strong verbal encouragement during the test 
 
 
D. MVC 
Select Muscle Group: Knee Extension/Flexion Right/Left 60° 
Test trial without recording 
 
INSTRUCTION: 
Strong – maximal extension/flexion 

 
 
 
Hold for 4–5 sec – may be built up gradually 
NO countermovement 
 
 
E. Test trial with recording (up to 3 if necessary) 
Measurement type: RFD 1 trial 
 
INSTRUCTION: 
Strong – maximal extension/flexion 
Hold for 4–5 sec – may be built up gradually 
NO countermovement 
 
 
F. MVC – 3× 4–5 sec with 30 sec pause 
 
At the computer: VICON TRIALTYPE: “EMG_MVC” 
Prepare Vicon filename: “MVC_quad_inj01” or “MVC_quad_heal01” 
Start recording on count “1” 
Mark as “good left” or “good right” 
 
Measurement type: GRASE_MVC 
Check correct pre- and pause-settings 
GIVE ALL INSTRUCTIONS (as in test trial) 
Start test → Zero level 
Countdown 3-2-1 (delayed from the screen) 
Strong verbal encouragement during the test 
 
G. Remove QUAD sensors carefully  
 
MVC External Rotators 
A. External Rotational Muscle Strength with Handheld Dynamometer 
Participant sits at the end of the bed with knees and hips in 90 degerees. 
 
INSTRUCTION: 
Trunk upright (must not lean sideways) 
Maximal force development – may be built up gradually 
A fist is placed between the participant’s knees to prevent hip abduction 
Handheld dynamometer placed on the inside of the lower leg (on the marked line) 

 
 
 
1–2 practice trials to 80% 
 
3 MVCs in external rotation performed with 30 sec pause between trials 
 
At the computer: Note measurements in test sheet 
 
HAMSTRINGS – EMG MVC 
 
A. EMG placement 
a. Palpate the muscle belly of BF and ST at the most prominent point 
v. Mark with surgical pen, scrape, and clean with alcohol 
b. Place EMG electrodes in the following order: 
EMG channel 
Muscle 
9 
Left BF 
10 
Left ST 
11 
Right BF 
12 
Right ST 
B. EMG MVC Hamstrings – 3x left and right 
a. Patient in Prone position with 10° knee flexion 
 
INSTRUCTION: 
Maximal force development – may be built up gradually 
1–2 test trials at 80% MVC 
3 MVCs in flexion performed with 30 sec pause between trials 
3D Recordings 
Isolated jumps  
 
All single-leg jumps are performed on both legs with starting leg decided by random draw. 
 
A. Marker placement 
CGM2.3 – 6 pelvis markers 
Put elastic sock on thigh to minimize artifacts.  

 
 
 
 
B. Static Measurement – 100 Hz 
Instruction in static position ( motor cycle pose) 
TRIALTYPE: “Static” 
Run Autoinitialize – step by step 
Save trial 
 
SWITCH TO 200 Hz AND TRIAL TYPE DYNAMIC 
 
C. RoM trial 
a. Participant performs 5 full extensions-flexions of each knee 
 
D. Horizontal 1-leg jump 
Filename: OLJ_inj01 or OLJ_heal01 
3 valid trials performed per side 
 
INSTRUCTION: 
Take-off from FP1 
Maximal horizontal hop 
Valid if landing is controlled (no moving the foot, no support from other leg or hands) 
Practice trials are given as needed 
 
At the computer: 
Mark as “good left” / “good right” 
Check that heel marker is in volume 
If not, note jump length from toe to toe 
 
E. Vertical 1-leg jump 
Filename: VOLJ_inj01 or VOLJ_heal01 
3 valid trials performed per side 
 
INSTRUCTION: 
Take-off from FP1 
Stand 1–2 sec before take-off for baseline 
Maximal vertical hop – center of mass, not just the leg 
Valid if landing within force plate 

 
 
 
Practice trials are given as needed 
 
At the computer: 
Mark as “good left” / “good right” 
 
 
F. Horizontal to Vertical Jump 
Filename: HVJ_inj01 or HVJ_heal01 
3 valid trials performed per side 
 
INSTRUCTION: 
Take-off from 100% mark 
Land on FP1 with immediate maximal vertical take-off 
Valid if landing within force plate 
Practice trials are given as needed 
 
At the computer: 
Mark as “good left” / “good right” 
 
 
G. Landing from Medial Rotation Hop 
Filename: MRH_inj01 or MRH_heal01 
3 valid trials performed per side 
 
INSTRUCTION: 
Take-off from 100% mark 
Land on FP1 with 90° medial rotation 
Valid if landing within force plate at 90 degrees on the take off postition and held for 2 sec. (no 
moving the foot, no support from other leg or hands). 
Practice trials are given as needed 
 
At the computer: 
Mark as “good left” / “good right” 
 
 

 
 
 
H. Countermovement Jump 
Filename: CMJ01 
3 valid trials performed 
 
INSTRUCTION: 
Participant with one foot on each force plate.  
Stand still for 2 sec 
Perform CMJ (starts from a standing position and initiates a downward movement, which is 
immediately fol- lowed by an upward movement leading to takeoff) 
Valid if landing in balance with one foot on each force plate. 
 
 
Functional Hop Test Cluster 
RECORDED IN VICON  
Start position adjusted to give a chance of hitting the force platform – but not required and not 
instructed to the patient.  
2 valid trials performed on each side starting with healthy leg 
 
 
 
 
 
A. Triple Hop for Distance (b) 
Filename: THD_inj01 or THD_heal01 
2 valid trials performed on each side 

 
 
 
 
INSTRUCTION: 
3 consecutive hops as far as possible 
Valid if landing is controlled (no moving the foot, no support from other leg or hands) 
             Distance marked at the toe 
             Practice trials on each leg as needed 
              
             At the computer: 
             Mark as “good left” / “good right” if there is a strike on the force platform 
             Note if the landing foot is in volume. 
 
 
B. Crossover Hop for Distance 
Filename: CHD_inj01 or CHD_heal01 
 
INSTRUCTION: 
3 consecutive hops as far as possible crossing the midline 
Valid if landing is controlled (no moving the foot, no support from other leg or hands) 
             Distance marked at the toe 
             Practice trials on each leg as needed 
 
             At the computer: 
             Mark as “good left” / “good right” if there is a strike on the force platform 
             Note if the landing foot is in volume. 
 
C. 3. Single Leg 6 meter Timed Hop 
NOT RECORDED in VICON 
 
INSTRUCTION: 
Single-leg Hop 6 meters for time 
Self-selected jump frequency and length.  

 
 
 
No requirement for controlled landing (just pass the 6 meter mark) 
Time starts at take-off – ends when jump leg passes the 6 meter mark. 
Practice trials on each leg as needed 
 
 
D. Side Cut (cutting maneuver)  
At 12 months – only for participants in handball and soccer 
Filename: SC_inj01 or SC_heal01 
3 valid trials on the force platform for each leg 
 
INSTRUCTION: 
Run towards the trash bin at high speed 
Cut on the force platform 
Practice trials on each leg as needed 
 
             At the computer: 
             Mark as “good left” / “good right” if there is a strike on the force platform 
      
 
 
 
 
 
 
 
 
 
 
 

 
 
 
GRASE ACL – Metitur settings 
 
 
a. LEG SUPPORT ANGLE (B): The knee joint angle is adjusted to 60 degrees of knee flexion, 
measured with a goniometer by the tester (Figure 6). This is read on a fixed measuring tape 
under the chair and entered into the computer (B). 
 
b. The ankle is fixed with a belt strap, which is adjusted to the mark 7 cm proximal to the 
lateral malleolus (Figure 8). 
 
c. LEG LEFT/RIGHT PLACEMENT: The degree of hip adduction and abduction is adjusted to 
ensure comfort for the test subject (approximately hip-width). 
 
d. Belt fixation is applied distally on the femur and around the pelvis. 
 
 
 
            
             
 
 
 
 
 
  
                
 
 
Figure 5: Starting position in the 
Metitur Good Strength (MGS) for 
measuring the Rate of Force 
Development of the hamstring 
muscles. 
Figure 6: The standardized 
distance from the edge of the 
chair to the popliteal fossa, 
along with the measurement of 
the knee joint angle (60 degrees) 
in the MGS. 
Figure 8: Ankle fixation with a belt strap 
at the marking for the lever arm in the 
MGS. 

 
 
 
Appendix 3 – Medical imaging protocol 
 
GRASE acl MRI-protocol 
Scan 
Leg length is measured before the first scan (by HBL) in two ways: 
From ASIS (anterior superior iliac spine) to the medial ankle malleolus 
From ASIS to the fibular head 
At each examination, the following scans must be performed: 
2 × axial PD-FS, 5/100% (5/5 mm) with 35 slices each (a total of 70 slices) 
1 × coronal T1, 4/10% (4/0.4 mm) with 50 slices 
For scanning, a vascular coil (Espree) is placed distally, and a body coil (Avanto) 
is placed proximally. 
Both legs are scanned simultaneously, and therefore the FOV (field of view) must 
be 500 × 500 mm (max). 
The scans are performed on an Avanto 1.5 T. 
The FOV must be positioned so that scanning covers from the upper edge of the 
fibular head and proximally (upwards). 
________________________________________ 
Image Processing 
When measuring the change in length of the semitendinosus (semi-T), 
compensation must be made for any pelvic tilt. This is verified by determining 
the position of the medial joint space bilaterally on the coronal scan. 
 
 
 
 
 

 
 
 
GRASE acl X-ray protocol 
Examination guide tibial slope: 
Acquire a true lateral projection, encompassing the proximal two-thirds of the 
tibia, to enable measurement of the angle between a line perpendicular to the 
mid-diaphyseal axis and the tangent to the medial tibial plateau. 
Should the images be forwarded? 
Images must be available in SP, Xero Viewer, and PACS. 
Should patient data be anonymised? 
No. 
Are accompanying documents required? 
No. 
Are there specific requirements for the report? 
No. 
How often should the examination be performed? 
Once per patient with suspected anterior cruciate ligament (ACL) injury. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
Appendix 4 – SMS-Survey questions 
Questions for SMS-track 
 
1 – In the past 2 weeks, have you visited a doctor or physiotherapist because of pain or 
discomfort in your operated knee? 
0 = No, 1 = Yes 
 
2 – How often have you had pain in your operated knee in the past 2 weeks? 
Never 0 1 2 3 4 5 6 7 8 9 10 All the time 
 
2a – How severe has your knee pain generally been in the past 2 weeks? 
No pain 0 1 2 3 4 5 6 7 8 9 10 Worst imaginable pain 
(Does not appear if they answered 0 or 1 in question 2.) 
 
3 – How much rehabilitation have you completed for your ACL surgery in the past 2 weeks? 
Minutes with a physiotherapist or other health professional present: 
Minutes doing home exercises: 
 
3b – Do you perform other knee-specific training or exercises (preventive/maintenance)? 
0 = No, 1 = Yes 
 
3c – Have pain or discomfort in your operated knee prevented you from completing your 
rehabilitation or knee-specific training exercises in the past 2 weeks? 
To a very high degree / To a high degree / To some degree / To a small degree / Not at all 
 
4 – How would you rate your maximum current physical/athletic/sporting function level? 
Cannot be physically active 0 1 2 3 4 5 6 7 8 9 10 Function level as when it was at its best 
 

 
 
 
4b – Have pain or discomfort in your operated knee prevented you from returning to your 
sport? 
To a very high degree / To a high degree / To some degree / To a small degree / Not at all 
 
5 – In the past 2 weeks, have you been on sick leave from work or education because of your 
ACL injury? 
Yes / No / I am not employed or in education 
 
5b – How would you rate your current physical work ability in the past 2 weeks? 
Unable to work at the moment 0 1 2 3 4 5 6 7 8 9 10 My work ability is as when it was at its best 
 
5c – Have pain or discomfort in your operated knee limited you in your work or education in 
the past 2 weeks? 
To a very high degree / To a high degree / To some degree / To a small degree / Not at all 
(Do not appear if they answered “I am not employed or in education” in question 5.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
Appendix 5 – Written information and Consent form 
 
 
 Participant Information for Participation in a Scientific Study  
Study Title: GRASE ACL – Optimizing GRAft SElection for ACL Reconstruction  
We would like to invite you to participate in a scientific study carried out by the Arthroscopic Center 
Hvidovre, the Gait Laboratory, and the Functional and Imaging Diagnostic Unit at Amager & Hvidovre 
Hospitals, in collaboration with University College Copenhagen. The study is initiated by Chief 
Consultant and Professor Per Hölmich.  
Before you decide whether to participate, it is important that you fully understand the purpose of the 
study and what participation will involve. We therefore ask you to read this participant information 
carefully.  
You will also receive detailed verbal information about the study from a member of the research team. 
If you have any questions that remain unanswered after reading this document, you are welcome to 
contact the research group using the contact details provided on the last page.  
If you decide to participate, you will be asked to sign an informed consent form. You are entitled to take 
time to consider your decision before signing.  
Participation is voluntary. You may withdraw your consent at any time without giving a reason, and this 
will not affect your further medical care.  
If you develop illness or sustain an injury to your musculoskeletal system that prevents you from 
completing the project’s tests or could otherwise influence the final results, we may need to withdraw 
you from the study. This will not affect your continued treatment. There are no anticipated reasons why 
the entire project would be terminated.  
Purpose of the Study  
The purpose of this study is to compare three different surgical techniques for reconstructing the 
anterior cruciate ligament (ACL). All three techniques are approved and used in standard clinical care. 
We aim to determine which method provides the best function and fewest problems during and after 
rehabilitation, as well as to investigate the underlying reasons.  
A total of 150 participants aged 18–40 years will take part in the study.  
 
Study Plan  
If you wish to participate and have signed the informed consent form, you will be randomly assigned to 
one of three groups, differing by the tendon used to create the new ACL – either from the hamstring 
muscles, the quadriceps tendon, or the patellar tendon.  
 

 
 
 
Before surgery, the operating surgeon will perform a standard clinical knee examination, and you will 
be asked to complete questionnaires regarding pain, self-perceived knee function, and fear of 
movement/exercise. These questionnaires will be repeated at 6, 12, and 24 months after surgery, along 
with additional questions about your ability to return to sports.  
At 6 and 12 months after surgery, you will undergo the same knee examination. In addition, you will 
complete a biomechanical test involving 3-D motion capture and surface EMG muscle activity 
measurements while performing physiotherapy-based tests, change-of-direction movements, and 
muscle strength tests. You will also undergo an MRI scan.  
All assessments will take place at Hvidovre University Hospital. We aim to schedule them on the same 
days as far as possible to minimize your time commitment. Completing the questionnaires is expected 
to take 1–1.5 hours, the clinical knee examination 30 minutes, the biomechanical test 2 hours, and the 
MRI scan 1 hour.  
After 12 months, the main part of your participation will end, and you will be offered feedback on your 
tests. You will, however, remain in the project until 24 months after surgery, when we will ask you to 
complete a selection of the same questionnaires again.  
During the study, we will request access to relevant notes in your medical record concerning your ACL 
injury, surgery, and postoperative progress. You will also be asked to answer two text messages per 
month during your rehabilitation, briefly asking about your knee function.  
 
Benefits of the Study  
The results may contribute important new knowledge for further optimizing ACL reconstruction 
techniques. This could potentially guide the development of individualized rehabilitation protocols 
depending on graft choice. The results may also help establish future surgical decision-making criteria 
to reduce the risk of complications and re-injury.  
For you personally, participation means closer follow-up during rehabilitation, with more frequent 
assessments and individual feedback on selected tests from the study. SKRIFTLIG  
 
 
 

 
 
 
Side Effects, Risks, Complications, and Inconveniences  
None of the assessments involve invasive procedures (such as biopsies or blood samples). MRI 
scanning is non-invasive and uses magnetic fields and radio waves; there are no known harmful 
effects.  
Standard X-rays will be taken. According to the Danish Patient Handbook, this will expose you to an 
amount of radiation equivalent to a few days of natural background radiation from the atmosphere, 
and is therefore considered negligible.  
After coordination and balance tests, you may experience mild temporary muscle soreness. However, 
no tests will be used that are not already applied in standard rehabilitation evaluation.  
The study will also require your time for assessments and travel to/from Hvidovre Hospital.  
There may be risks we are not yet aware of. You are therefore asked to report any health problems you 
experience during the study. If we discover any new side effects not mentioned here, you will be 
informed immediately, and you will be asked to decide whether you wish to continue.  
Financial Information  
The project is based at the Orthopaedic Surgery Department, Amager and Hvidovre Hospitals. The 
collaborating partners are all experienced in their respective fields, ensuring high research quality. All 
project staff are fully funded by Hvidovre Hospital and the Novo Nordisk Foundation to carry the 
project through to completion.  
Access to Study Results  
The results will be published in academic journals and presented at conferences. They will also be 
communicated to orthopaedic surgeons and physiotherapists in Denmark and internationally.  
At the end of the project, a summary written for study participants will be prepared.  
We hope this information has given you sufficient insight into what participation will involve and that 
you feel prepared to make your decision. Please also read the enclosed material "The Rights of the 
Research Participant in a Health Science Research Project".  
 
If you would like more information, please feel free to contact:  
Merete Brink Speedtsberg Email: merete.brink.speedtsberg@regionh.dk Phone: 38 62 23 81  
Cecilie Køllner Olsen Email: cecilie.koellner.olsen.01@regionh.dk Phone: 24 89 91 15  
Kind regards, on behalf of the GRASE ACL Project Merete Brink Speedtsberg & Cecilie Køllner Olsen 
 
 
 
 

 
 
 
Research Project Title: GRASE ACL: Optimizing GRAft SElection in ACL Reconstruction  
Declaration by the Participant:  
I have received written and oral information, and I know enough about the purpose, method, benefits, 
and disadvantages to agree to participate.  
I understand that participation is voluntary, and that I may withdraw my consent at any time without 
losing my current or future rights to treatment.  
I consent to participate in the research project and have received a copy of this consent form as well 
as a copy of the written project information for my own use.  
Participant’s Name: ___________________________________________  
Date: _______________ Signature: ___________________________________________  
Would you like to be informed about the results of the research project and any possible 
consequences for you? YES ______ (tick) NO ______ (tick)  
May the project use video and image material of you for teaching purposes and communication 
of the project results? YES ______ (tick) NO ______ (tick)  
Access to Medical Records:  
I have received written and oral information about what information will be obtained from my medical 
records, and I consent to the project staff having access to my records from today’s date, as well as 
contacting me once a year for five years to obtain renewed consent for access to my records regarding 
the current injury.  
Participant’s Name: ___________________________________________  
Date: _______________ Signature: ___________________________________________  
Declaration by the Person Providing the Information:  
 
I declare that the participant has received verbal and written information about the research project. In 
my opinion, sufficient information has been provided for the participant to make a decision about 
participating in the study.  
Name of Person Providing Information: ____________________  
Date: _______________ Signature: ___________________________________________