Knee Injuries
Conditions
Keywords
Cartilage repair, Cartilage, Knee, Knee Pain, Microfracture, arthroscopy, bone marrow stimulation, Chondrogenesis, Scaffold, Chitosan, A02.165.165, A10.165.382.332, G07.574.500.325.377.625.180, A10.165.382.400, Articular Cartilage Repair
Brief summary
This study will investigate whether the treatment of damaged cartilage in the knee with BST-CarGel will increase the amount and quality of cartilage repair tissue when compared with microfracture alone. Furthermore, the effect of BST-CarGel in decreasing cartilage related pain and improving cartilage-related function in the knee will be assessed.
Detailed description
Cartilage repair currently remains a problematic orthopedic concern with no effective solution. The development of new surgical techniques or therapies is critical in meeting this medical need. This Canadian trial will be a pivotal protocol study, conducted as a randomized, controlled trial. A total of 80 subjects, 40 subjects in each of the two groups (BST-CarGel applied to a microfractured lesion or microfracture alone), will be enrolled in this study. The subjects and investigative medical staff will not be blinded to treatment due to the difference in surgical incision size. However, although the treatment will not be blinded, the primary effectiveness assessment will be blinded. The primary endpoint of this study will be cartilage repair at 12 months proved by demonstrating that BST-CarGel treatment effectively fills cartilage lesions with high quality cartilaginous tissue. The secondary endpoints will be pain, stiffness and function while other tertiary endpoints will include safety, quality-of-life (QOL), as well as macroscopic characterizations of tissue repair. The primary measure of this study will occur at 12 months, when imaging of repair tissue using magnetic resonance (MR) and associated analyses will compare tissue volume, quality and other anatomical variables. Radiographic evaluations will be blinded. Volunteer biopsies at 13 months may be obtained. Pain, stiffness, function and QOL will be assessed prior to treatment, and at 3, 6 and 12 months following treatment using self-administered validated scores (WOMAC and SF-36). In addition, subject safety will be assessed through a record of adverse events.
Interventions
DEVICEBST-CarGel with Microfracture
Microfracture performed with BST-CarGel added to the treated defect
PROCEDUREMicrofracture without BST-CarGel
Microfracture performed without BST-CarGel added to the treated defect.
Sponsors
Piramal Healthcare Canada Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 55 years of age * Focal articular cartilage lesion on the medial femoral condyle * Grade 3 or 4 acute (traumatic) or chronic (degenerative) lesion * Stable knee
Exclusion criteria
* Multiple lesions or kissing lesions * Clinically relevant compartment malalignment (\> 5 degrees) * Undergone ligament treatments in the affected knee within 2 years prior to trial * Inflammatory arthropathy, such as rheumatoid arthritis, systemic lupus, or active gout * Previous surgical cartilage treatments in the affected knee in the last 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of Filling of the Lesion by Repair Tissue at 12 Months Through MRI. | 12 months | Evaluate the efficacy of BST-CarGel® applied to a microfractured lesion as compared to microfracture alone on the degree of lesion filling of the study knee in subjects with symptomatic pain associated with cartilage damage using MRI scans. The MR images will be acquired using high resolution 3D cartilage imaging sequences, so-called cartilage morphology sequences. |
| Repair Cartilage T2 Relaxation Time | 12 months | Evaluate the efficacy of BST-CarGel® applied to a microfractured lesion as compared to microfracture alone on the repair tissue quality of the study knee in subjects with symptomatic pain associated with cartilage damage using MRI T2 mapping. T2 maps are created by calculating the T2 relaxation times for repair tissue and cartilage plates for every voxel (picture element of a MRI scan containing the average signal information of a specific spatial location of the imaged body). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | 12 months | The three sub-scales: 1) Pain, 2.) stiffness and 3.) function scores ranged from 0-10. Pain had 5 items and stiffness had 2 items, and function had 17 items. The total score for pain ranged from 0 no pain to 50 worst pain. The total score for stiffness ranged from 0 no stiffness to 20 worst stiffness. The total score for function raged from 0 no function to 170 worst function. |
| Frequency of Adverse Events Between Study Groups | 12 months | — |
Countries
Canada, South Korea, Spain
Participant flow
Recruitment details
Subjects were recruited from May 04, 2006 to January 2009 from orthopaedic surgeon referrals across 24 centers across Canada, Europe, and South Korea.
Pre-assignment details
Subjects were stratified by site and lesion type (acute/chronic) to address possible repair differences. Final eligibility and lesion type were determined during diagnostic arthroscopy at treatment visit, subjects were randomized to BST-CarGel or MFX treatment using a computer-generated randomization schedule to ensure a 1:1 ratio within each site.
Participants by arm
| Arm | Count |
|---|---|
| Experimental BST-CarGel applied to a Microfractured lesion | 41 |
| Control Microfracture alone | 39 |
| Total | 80 |
Baseline characteristics
| Characteristic | Experimental | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 39 Participants | 80 Participants |
| Age, Continuous | 35.1 years STANDARD_DEVIATION 9.6 | 37.2 years STANDARD_DEVIATION 10.6 | 36.1 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment Canada | 33 participants | 32 participants | 65 participants |
| Region of Enrollment Korea, Republic of | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Spain | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 32 Participants |
| Sex: Female, Male Male | 23 Participants | 25 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 41 | 36 / 39 |
| serious Total, serious adverse events | 5 / 41 | 1 / 39 |
Outcome results
Primary
Degree of Filling of the Lesion by Repair Tissue at 12 Months Through MRI.
Evaluate the efficacy of BST-CarGel® applied to a microfractured lesion as compared to microfracture alone on the degree of lesion filling of the study knee in subjects with symptomatic pain associated with cartilage damage using MRI scans. The MR images will be acquired using high resolution 3D cartilage imaging sequences, so-called cartilage morphology sequences.
Time frame: 12 months
Population: Sample size for degree of lesion filling was calculated using a standard t test, with an anticipated relevant difference of 15% between treatments and a common SD of 15. Under these assumptions, the sample size per group was calculated to be 23 subjects (or 46 subjects in total)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Degree of Filling of the Lesion by Repair Tissue at 12 Months Through MRI. | 92.81 Percentage of lesion fill | Standard Error 1.98 |
| Control | Degree of Filling of the Lesion by Repair Tissue at 12 Months Through MRI. | 85.22 Percentage of lesion fill | Standard Error 2.08 |
p-value: 0.011ANCOVA
Primary
Repair Cartilage T2 Relaxation Time
Evaluate the efficacy of BST-CarGel® applied to a microfractured lesion as compared to microfracture alone on the repair tissue quality of the study knee in subjects with symptomatic pain associated with cartilage damage using MRI T2 mapping. T2 maps are created by calculating the T2 relaxation times for repair tissue and cartilage plates for every voxel (picture element of a MRI scan containing the average signal information of a specific spatial location of the imaged body).
Time frame: 12 months
Population: Sample size for repair tissue quality was calculated, using a standard t test, with an anticipated relevant difference of 15% between treatments and a common SD of 10. Under these assumptions, the sample size per group was calculated to be 11 subjects (or 22 subjects in total)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Experimental | Repair Cartilage T2 Relaxation Time | 70.46 milliseconds | Standard Error 4.49 |
| Control | Repair Cartilage T2 Relaxation Time | 85.04 milliseconds | Standard Error 4.89 |
p-value: 0.033ANCOVA
Secondary
Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C)
The three sub-scales: 1) Pain, 2.) stiffness and 3.) function scores ranged from 0-10. Pain had 5 items and stiffness had 2 items, and function had 17 items. The total score for pain ranged from 0 no pain to 50 worst pain. The total score for stiffness ranged from 0 no stiffness to 20 worst stiffness. The total score for function raged from 0 no function to 170 worst function.
Time frame: 12 months
Population: Secondary efficacy was evaluated based on pain, stiffness, and function, as well as the macroscopic nature of the cartilage repair. Measurements of pain, stiffness, and function were made at 3, 6, and 12 months post-treatment using the WOMAC questionnaire and SF-36v2. WORMS scoring was conducted on 12-month post-treatment MRI scans.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Function | -55.96 Units on a scale | Standard Error 4.24 |
| Experimental | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Pain | -16.16 Units on a scale | Standard Error 1.16 |
| Experimental | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Stiffness | -5.97 Units on a scale | Standard Error 0.68 |
| Control | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Stiffness | -6.56 Units on a scale | Standard Error 0.71 |
| Control | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Function | -60.59 Units on a scale | Standard Error 4.41 |
| Control | Change From Baseline for Knee-related Pain, Stiffness and Function at 12 Months (WOMAC Parts A, B, C) | Pain | -16.91 Units on a scale | Standard Error 1.21 |
Secondary
Frequency of Adverse Events Between Study Groups
Time frame: 12 months
Population: AEs will be coded and tabulated separately by system organ class (SOC) and individual preferred terms (PTs). The number and percentage of subjects who experienced AEs will be summarized in decreasing frequency by using the medical dictionary for regulatory activities (MedDRA) dictionary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental | Frequency of Adverse Events Between Study Groups | 97.6 Percentage of participants |
| Control | Frequency of Adverse Events Between Study Groups | 92.3 Percentage of participants |