Tunnel Widening in Augmented ACL Integration Via PrP Enriched Collected Autologous Bone vs Standard ACL Technique

Study Overview
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Brief Summary
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The purpose of this clinical study is to compare the outcomes of two surgical techniques for reconstruction of the anterior cruciate ligament (ACL) after a single, primary ACL rupture. The main question to be answered is: - Does less widening of the tibial tunnel occur when a bone/Platelet rich plasma (PrP) composite material is placed directly into the tibial tunnel after fixation of the implant (experimental group) compared to the same surgery without the use of the composite material (control group)? Participants will be randomized into one of the two groups and they will not know which group they belong to. After 12 months they will undergo CT, MRI, medical examination and functional knee testing. They will have a further medical examination and functional knee testing at 24 months. Patient Reported Outcomes will be collected before surgery, 6, 12 and 24 months after surgery.

Detailed Description
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To be successful, an ACL reconstruction requires a strong incorporation of the tendon to the bone within or at the margin of the tunnel, but the tunnel itself is at risk of widening, therefore compromising the tendon attachment. A composite of harvested healthy autologous bone fragments from the tunnel and autologous thrombin and fibrin, generated from the patient's PrP could be used at the interface between tunnel and ACL graft at the tibia and femur to reduce frequency of tunnel widening and therefore improve graft-bone-integration. The study seeks primarily to determine less tibial tunnel widening when a bone/PrP-composite is applied directly in the tibial tunnel compared to the same surgery without using the composite, measured with CT and MRI. Secondary study objectives are to evaluate femoral tunnel widening, tibial and femoral graft incorporation, graft maturation and knee function (clinical, functional, patient reported) over the course of 24 months follow-up and to evaluate occurrence of procedure- and product-related adverse events and complications. This is a prospective, single-center, single-blinded, 2-arm-parallel, randomized, controlled study with 24 months follow-up. Participants will be recruited from the Knee Surgery department at Schulthess Klinik when scheduled for ACL reconstruction. The study sample comprises 107 patients, allocated 1:1 on experimental and control arm. Outcome measures are taken at 0, 6, 12, and 24 months. The total study duration is 48 months. The study duration per patient is 24 months.

Official Title
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A Single-center, Patient-blinded, Randomized, 2-year, Parallel-group, Superiority Study to Compare the Efficacy of Augmented ACL Integration Via Platelet-rich-plasma Enriched Collected Autologous Bone Versus Standard ACL Technique

Conditions
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Anterior Cruciate Ligament Tear

Intervention / Treatment
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* Procedure: ACL reconstruction with bone/PrP-composite
* Procedure: ACL reconstruction (Standard)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-50 years Primary ACL rupture Time from injury to surgery: 4 weeks to 6 months Single ACL rupture (isolated rupture) ACL surgery with one of the participating senior surgeons Informed Consent as documented by signature Exclusion Criteria: Concomitant ligamentous instability/rupture Requirement for Meniscus suture (partial resection accepted, hoop and roots remain intact) Requirement for cartilage invasive treatment (debridement accepted) Osteoarthritis at index knee joint Leg axis deviation over 3° valgus or 4° varus Claustrophobia (contra-indication for the MRI) Women who are pregnant or breast feeding or intention to become pregnant during the study Known or suspected non-compliance, drug or alcohol abuse Inability of the patient to follow the study procedures, e.g. language problems, psychological disorders, dementia, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be allocated 1:1 on experimental and control arm using block randomization within both genders with random block sizes (randomly chosen from the set [2,4,6,8]).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACLr with bone/PrP-composite<br>During surgery, the drilled bone debris is collected in a sterile filtered chamber. Then the bone debris is mixed with PrP. After fixation of the graft the composite is inserted into the drilled tunnel at the interface between tendon to bone. The intraarticular aperture sites are sealed by use of fibrin that is previously gathered out of the PrP as well. | Procedure: ACL reconstruction with bone/PrP-composite<br>* During standard ACL reconstruction, the drilled bone debris is collected in a sterile filtered chamber. Then the bone debris is mixed with PrP. After fixation of the graft the composite is inserted into the drilled tunnel at the interface between tendon to bone. The intraarticular aperture sites are sealed by use of fibrin that is previously gathered out of the PrP as well.<br>|
| Active Comparator: ACLr standard<br>No insertion of additional material after ACL graft fixation. | Procedure: ACL reconstruction (Standard)<br>* Standard ACL reconstruction with Semitendinosus alone or plus gracilis, femoral fixation via extracortical fixation by adjustable loop device, tibial fixation via a bio-interference screw or adjustable device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tibial tunnel diameter change | Diameter (mm) change of tibial tunnel in relation to tunnel diameter reported from surgery; assessed by one radiologist (CT); CT scanning is performed from a level just above the femoral external foramen to a level below the outer hole of the tibial tunnel in order to visualise the positioning of the autograft-fixing metallic devices. The scan is aligned so that the tunnel axis is in the sagittal plane. The diameter of the headed reamer that drilled the tibial tunnel is defined as the baseline diameter of the tibial tunnel (D0). Measurements are taken at 4 different levels for the tibial tunnels using 3D Multiplanar reconstruction. All diameters are calculated in mm within the measurement function of the picture archiving system. The percentage of widening is defined as the difference between initial drilling diameter D0 (derived from surgery report) and post-op measurements D12 in relation to initial drilling diameter D0. | 10 to 14 months post-surgery | 
| Tibial tunnel volume change | Volume (mm^3) change of tibial tunnel in relation to tunnel volume reported from surgery; assessed by one radiologist (CT); the border of the bone tunnel is drawn manually on every fourth slice in both the coronal plane and the sagittal plane and interpolated automatically in between. Based on the contours in those two planes, the contours in the axial plane are interpolated automatically into a 3D mask. The volume of the bone tunnel is determined by automatic voxel counting^. | 10 to 14 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Femoral tunnel diameter change | Diameter (mm) change of femoral tunnel in relation to tunnel diameter reported from surgery; assessed by one radiologist (CT); CT scanning is performed from a level just above the femoral external foramen to a level below the outer hole of the tibial tunnel in order to visualise the positioning of the autograft-fixing metallic devices. The scan is aligned so that the tunnel axis is in the sagittal plane. The diameter of the headed reamer that drilled the femoral tunnel is defined as the baseline diameter of the femoral tunnel (D0). Measurements are taken at 4 different levels for the femoral tunnels using 3D Multiplanar reconstruction. All diameters are calculated in mm within the measurement function of the picture archiving system. The percentage of widening is defined as the difference between initial drilling diameter D0 (derived from surgery report) and post-op measurements D12 in relation to initial drilling diameter D0. | 10 to 14 months post-surgery | 
| Femoral tunnel volume change | Volume (mm^3) change of femoral tunnel in relation to tunnel volume reported from surgery; assessed by one radiologist (CT); the border of the bone tunnel is drawn manually on every fourth slice in both the coronal plane and the sagittal plane and interpolated automatically in between. Based on the contours in those two planes, the contours in the axial plane are interpolated automatically into a 3D mask. The volume of the bone tunnel is determined by automatic voxel counting. | 10 to 14 months post-surgery | 
| Graft maturity_subj | tibial & femoral, subjectively, using a 4-grade system MRI after 12 months based on Proton-density-weighted images Grade 1 signal (normal): when the entire segment of graft has a homogeneous, low intensity signal indistinguishable from that of the posterior cruciate ligament Grade 2: if the segment of graft retained at least 50% of normal ligament signal intermixed with portions of the graft that had become edematous, as indicated by areas of increased signal intensity Grade 3: when a segment of graft had  50% of its area exhibiting a normal appearing ligament signal Grade 4: diffuse increase in signal intensity with no normal-looking strands of ligament (100% oedematous). | 10 to 14 months post-surgery | 
| Graft maturity_obj | objectively, within the tibial and femoral tunnels and in the intra-articular portion using the mean intensity of a region of interest on MRI to estimate the graft signal to noise quotient (SNQ) in comparison to the quadriceps tendon: SNQ = Signal intensity graft - Signal intensity quadriceps tendon / SI background | 10 to 14 months post-surgery | 
| Graft integration | tibial & femoral, Grade I, full attachment of a low-intensity signal band onto the bone tunnel with no fibrous tissue at the tendon-bone interface; Grade II, a low-intensity signal band with a partial high- intensity signal band at the tendon-bone interface; Grade III, the graft bone interface is filled with a continuous high- intensity signal band. | 10 to 14 months post-surgery | 
| Bone healing and integration | subjectively, tibial & femoral, of the applied autologous bone matrix Grade I, excellent integration indicating no space between the graft and osseous formation in the proximal and mid portion. Grade II, good integration indicating no space between the graft and osseous formation in the proximal or mid portion. Grade III, fair integration indicating a gap between the graft and osseous formation in the proximal and mid portion. Grade IV, poor integration indicating no osseous formation in the proximal and mid portion. | 10 to 14 months post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anterior Cruciate Ligament Reconstruction, Platelet-Rich Plasma, Bone Tunnel Widening