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

Primary Purpose

Anterior Cruciate Ligament Tear

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
ACL reconstruction with bone/PrP-composite
ACL reconstruction (Standard)
Sponsored by
Schulthess Klinik
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anterior Cruciate Ligament Tear focused on measuring Anterior Cruciate Ligament Reconstruction, Platelet-Rich Plasma, Bone Tunnel Widening

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    ACLr with bone/PrP-composite

    ACLr standard

    Arm Description

    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.

    No insertion of additional material after ACL graft fixation.

    Outcomes

    Primary Outcome Measures

    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.
    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^.

    Secondary Outcome Measures

    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.
    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.
    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).
    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
    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.
    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.

    Full Information

    First Posted
    June 29, 2023
    Last Updated
    July 11, 2023
    Sponsor
    Schulthess Klinik
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05953051
    Brief Title
    Tunnel Widening in Augmented ACL Integration Via PrP Enriched Collected Autologous Bone vs Standard ACL Technique
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2023 (Anticipated)
    Primary Completion Date
    August 2026 (Anticipated)
    Study Completion Date
    August 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Schulthess Klinik

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Anterior Cruciate Ligament Tear
    Keywords
    Anterior Cruciate Ligament Reconstruction, Platelet-Rich Plasma, Bone Tunnel Widening

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    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
    ParticipantOutcomes Assessor
    Masking Description
    Patients are blinded. As well, staff conducting and evaluating MRI, clinical evaluation, CT and functional tests are blinded.
    Allocation
    Randomized
    Enrollment
    107 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    ACLr with bone/PrP-composite
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    ACLr standard
    Arm Type
    Active Comparator
    Arm Description
    No insertion of additional material after ACL graft fixation.
    Intervention Type
    Procedure
    Intervention Name(s)
    ACL reconstruction with bone/PrP-composite
    Intervention Description
    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.
    Intervention Type
    Procedure
    Intervention Name(s)
    ACL reconstruction (Standard)
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Tibial tunnel diameter change
    Description
    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.
    Time Frame
    10 to 14 months post-surgery
    Title
    Tibial tunnel volume change
    Description
    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^.
    Time Frame
    10 to 14 months post-surgery
    Secondary Outcome Measure Information:
    Title
    Femoral tunnel diameter change
    Description
    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.
    Time Frame
    10 to 14 months post-surgery
    Title
    Femoral tunnel volume change
    Description
    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.
    Time Frame
    10 to 14 months post-surgery
    Title
    Graft maturity_subj
    Description
    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).
    Time Frame
    10 to 14 months post-surgery
    Title
    Graft maturity_obj
    Description
    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
    Time Frame
    10 to 14 months post-surgery
    Title
    Graft integration
    Description
    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.
    Time Frame
    10 to 14 months post-surgery
    Title
    Bone healing and integration
    Description
    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.
    Time Frame
    10 to 14 months post-surgery
    Other Pre-specified Outcome Measures:
    Title
    Range of motion
    Description
    extension and flexion (°) both knees
    Time Frame
    10-14 and 20-28 months post-surgery
    Title
    Isokinetic knee strength test
    Description
    Extension and Flexion (Nm), operated vs. non-operated side
    Time Frame
    10-14 and 20-28 months post-surgery
    Title
    Knee Laxity
    Description
    the patient is placed in the supine position on an examination table, the knees remain at approximately 30° of flexion and the tibia a 15° rotation. The displacement is consequently measured with the KT-1000 arthrometer device, calculating the relative motion between the sensor pad on the patella and the sensor pad on the anterior tibia under 67, 89 and 134 N force. The healthy leg is always to be tested first followed by the injured leg. The side-to-side differences are then evaluated at each force (mm)
    Time Frame
    10-14 and 20-28 months post-surgery
    Title
    gait restrictions
    Description
    gait restrictions related to the operated knee (i.e. limping) (y/n)
    Time Frame
    10-14 and 20-28 months post-surgery
    Title
    adverse events
    Description
    procedure- and product-related adverse events will be described and given as frequency per type
    Time Frame
    10-14 and 20-28 months post-surgery
    Title
    European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
    Description
    standardized instrument for measuring generic health status regardless of existing diseases within five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), result is a 5-level health state
    Time Frame
    -3 to 0, 6, 12, 24 months post-surgery
    Title
    EuroQol visual analogue scale (EQ-VAS)
    Description
    Quality of life, regardless of existing diseases, visual analogue scale from 0 - 100. 0 points correspond to the worst possible health status, while 100 points correspond to the best possible health status.
    Time Frame
    -3 to 0, 6, 12, 24 months post-surgery
    Title
    Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description
    assess patient-relevant outcomes following knee injury using 42 items within 5 subscales, which are scored separately; each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.
    Time Frame
    -3 to 0, 6, 12, 24 months post-surgery
    Title
    Tegner Activity Scale
    Description
    one-item score that grades activity based on work and sports activities on a scale of 0 (disability because of knee problems) to 10 (national or international elite level)
    Time Frame
    12, 24 months post-surgery
    Title
    Return to Sport Injury Scale (ACL-RSI)
    Description
    the patient's self-confidence and risk assessment regarding a return to sport after ACL reconstruction with 12 items using a numeric rating scale of 0 to 100.
    Time Frame
    12, 24 months post-surgery
    Title
    Numeric Rating scale for pain (NRS) in the knee
    Description
    unidimensional measure of pain intensity in adults, where 0=no pain and 10=worst possible pain
    Time Frame
    -3 to 0, 6, 12, 24 months post-surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Vincent A Stadelmann, PhD
    Phone
    +41 44 385
    Ext
    75 87
    Email
    vincent.stadelmann@kws.ch
    First Name & Middle Initial & Last Name or Official Title & Degree
    Anika Stephan, MA
    Phone
    +41 44 385
    Ext
    79 84
    Email
    anika.stephan@kws.ch
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gian Salzmann, Prof.
    Organizational Affiliation
    Schulthess Klinik
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    When published, authors will make their data available upon reasonable request or according to the guidelines of the journal.

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

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