Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01803880
Other study ID # SM-2012-02
Secondary ID
Status Terminated
Phase N/A
First received
Last updated
Start date March 8, 2013
Est. completion date July 21, 2017

Study information

Verified date March 2019
Source Smith & Nephew, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate changes in clinical and imaging outcomes following arthroscopic treatment of a single medial femoral chondral lesion plus partial medial meniscectomy by Radiofrequency-Based debridement or Mechanical Debridement in subjects ≥ eighteen (18) years of age.


Description:

This is a non-inferiority, prospective, double blinded, multi-center, randomized, controlled, adaptive study design with enrollment of 82 randomized subjects at up to 13 study sites. Study duration will be until the last subject enrolled reaches 104 weeks post-operative.

The study will be comprised of two parts:

Part I: Part I will require all Investigators perform 1 to 3 procedures using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Investigators must be qualified by training to perform procedures prior to use of either study device. This purpose of Part I will be to minimize variability with the recommended directions for use established in the instructions for use (IFU). Part I subjects will be followed per protocol follow-up requirements, and will be included in the safety population only. These subjects will be additive (to the safety population) to the 82 randomized subjects planned as part of the primary evaluation in Part II.

Part II: Part II will consist of 82 randomized subjects. Each Investigator may initiate enrollment of subjects in this part of the study following completion of Part I requirements. The Part II study implements a randomized adaptive study design, whereby an interim analysis will be conducted for sample size re-assessment. There is no intention of reducing the sample size as a result of this interim analysis; however, the sample size may be increased to either establish the non-inferiority and/or may be increased sufficiently to establish superiority depending on the results of the interim analysis.


Recruitment information / eligibility

Status Terminated
Enrollment 148
Est. completion date July 21, 2017
Est. primary completion date May 4, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria

Subjects MUST meet ALL of the following criteria to be included in the study:

1. Given written informed consent on the IRB/REB approved Consent Form specific to the study, prior to study participation

2. Is male or non pregnant female = eighteen (18) years of age

3. MRI within 9 months of enrollment into this study confirming presence of a medial femoral chondral lesion and medial meniscal tear requiring a partial meniscectomy (as determined by the Investigator)

4. Must present with pain in the index knee of moderate or severe (> 30 mm) as measured by the VAS

5. Must be able to understand English (written and oral)

6. Must be available to come to all study related visits and is physically and mentally willing and able to comply with all post-operative evaluations

7. Must be in general good health (as determined by the Investigator) based on screening assessments and medical history

Intra-operative Inclusion Criteria

Subjects MUST meet ALL of the following criteria to be included in the study:

1. Arthroscopic confirmation of a lesion requiring treatment meeting the following parameters:

1. Single, treatable chondral lesion, localized to the medial femoral condyle,

2. ICRS Grade 2 with widely displaceable fibrillation or flaps or Grade 3A,

3. < 4cm2 in size

Exclusion Criteria

Subjects will be excluded from the study, if they meet ANY one (1) of the following criteria:

1. Body Mass Index (BMI) > 40 or index joint pain is due to BMI (as determined by Investigator)

2. Requires bilateral knee surgery

3. Any of the following conditions:

1. active joint infections

2. is immunocompromised, has Sickle Cell disease, has a primary bone disease (e.g., Paget's disease) or disorders that may adversely affect the healing process, or is terminally ill

3. inflammatory rheumatoid arthritis or other systemic inflammatory arthritis (i.e., gout)

4. metastatic and/or neoplastic disease

5. infectious, highly communicable diseases (e.g., active tuberculosis or active hepatitis)

6. coagulation disorder or patient is receiving anti-coagulants

7. documented evidence of a history (e.g. liver testing) of drug/alcohol abuse within 12 months of enrollment into this study

8. diagnosed with a behavioral condition which could affect their ability to accurately comply with the study (e.g. developmental delay, attention deficit disorder, and autism)

4. Any of the following conditions in the index limb or joint:

1. Grade III or greater osteoarthritis as determined by AP radiograph (Kellgren-Lawrence classification)

2. systemic steroid therapy or steroid intra-articular therapy within 4 weeks of enrollment into this study

3. intra-articular viscosupplementation within 3 months of enrollment into this study

4. osteomyelitis, septicemia, or other infections that may spread to other areas of the body

5. fractures, osteocysts or osteolysis

6. recurrent patellar instability (e.g., subluxation or dislocation)

7. severe Varus or Valgus knee deformities (as determined by Investigator)

8. symptomatic tear of the lateral meniscus

9. avascular necrosis

10. synovial disorders (e.g., pigmented villanodular synovitis)

11. previous total or partial meniscectomy

12. requires reconstruction or replacement of medial or lateral meniscus

13. knee instability, malalignment, or patellar tracking dysfunction

14. prior treatment for cartilage repair, including but not limited to ACI, Mosaicplasty and/or marrow stimulation procedures

15. prior knee tendon and/or ligament repair or patellar surgery within 6 months of enrollment into this study

5. Any of the following conditions in the contralateral limb or joint:

1. greater than minimal abnormality as shown by clinical exam and/or imaging

2. scheduled or to be scheduled for surgery over the course of this study

3. involvement causing abnormal ambulation and non-compliance with post-operative rehabilitation guideline

6. The subject has implanted metallic devices (insulin pumps, nerve stimulators, etc), medically implanted clips or other electronically, magnetically or mechanically activated implants that would contraindicate undergoing an MRI scan of the knee

7. The subject has claustrophobia that would inhibit their ability to undergo an MRI scan of the index knee

8. Receiving prescription narcotic pain medication for conditions unrelated to the index knee condition

9. Cardiac pacemaker or other electronic implant(s)

10. Pregnant and/or intending to become pregnant during this study period

11. Participated in a clinical study within 30 days of enrollment into this study, or who is currently participating in another clinical study.

12. Is a prisoner, or is known or suspected to be transient

13. Is involved with Worker's Compensation unrelated to the index knee

14. Is involved with health-related litigation

Intra-operative Exclusion Criteria

Subjects will be excluded from the study, if they meet ANY one (1) of the following criteria:

1. Has more than 1 chondral lesion requiring treatment

2. Requires concomitant procedures (i.e., anterior cruciate ligament repair, high tibial osteotomy), excluding partial medial meniscectomy

3. Has a medial meniscal tear not requiring treatment

4. Has a medial meniscal tear requiring a procedure other than partial meniscectomy

5. Has a lateral meniscal tear requiring treatment

Study Design


Related Conditions & MeSH terms

  • Chondral Lesion Plus Partial Medial Meniscectomy

Intervention

Device:
Mechanical Debridement
mechanical shaver that removes areas of damaged tissue
RF-Based Debridement
Electrical energy that removes areas of damaged tissue (Coblation®)

Locations

Country Name City State
United States Ohio State University Columbus Ohio
United States Orthopaedic Research Foundation, Inc. Greenwood Indiana
United States Andrews Research and Education Foundation, Inc. Gulf Breeze Florida
United States Methodist Center For Orthopedic Surgery Houston Texas
United States Basin Orthopedic Surgical Specialists Odessa Texas
United States University Orthopedics Center State College Pennsylvania
United States Tucson Orthopaedic Institute Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Smith & Nephew, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline in Knee and Osteoarthritis Outcomes Scores (KOOS) at Week 52 Post-operative The scores of 5 subscales of KOOS (i.e., Pain, other Symptoms, Function in daily living [ADL], Function in Sport and Recreation [Sport/Rec] and knee related Quality of Life [QoL]) at Baseline, Week 52 and change from Baseline were summarized descriptively by treatment group. The average of KOOS subscale scores was considered as the primary endpoint. For any subject if the value of effectiveness parameter was missing at Week 52 then it was imputed by last observed post-Baseline value (LOCF method).
Each subscale response is based on a 5-point Likert system with each response score ranging from 0 (no problems) to 4 (extreme problems). Each subscale score is calculated independently. A score of 100 indicated no problems and a score of 0 indicated extreme problems.
KOOS subscale score = 100 - (mean of the observed items within the subscale x100 / 4)
Postop Week 52
Secondary Change in International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form Scores From Baseline. The scores of three domains of IKDC Subjective Knee Evaluation Form (i.e., [1] symptoms, including pain, stiffness, swelling, locking/catching, and giving way; [2] sports and daily activities; and [3] current knee function) at Baseline, each of scheduled post-operative visits and changes from Baseline were summarized descriptively by treatment group.
Change from Baseline in IKDC = IKDC at Baseline + Pseudo-site + Treatment + Treatment*Pseudo-site
The IKDC score was interpreted by summing the scores for the individual questions and then transforming the score to a scale that ranged from 0 to 100:
Individual domain IKDC score = [raw score - lowest possible score/range of scores] x 100
The IKDC total score was interpreted as higher scores = higher function, lower scores = lower function.
Treatment*Pseudo-site interaction term was non-significant at the 0.05 level and hence was dropped from the statistical method.
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/Early Termination (ET)
Secondary Number of Participants Stratified by Generalized Laxity Level on IKDC Knee Evaluation Knee examination with respect to generalized laxity (tight, normal, lax) were summarized as number and percent of subjects in treatment group for Baseline and post-operative follow-up visits.
The IKDC Knee Evaluation Form was comprised of 3 domains: 1) symptoms including pain, stiffness, swelling, locking/catching, and giving way; 2) sports and daily activities; and 3) current knee function and knee function prior to knee injury.
There were 18 questions and the raw score was transformed to a 0 to 100 scale score as follows:
IKDC score = (raw score - lowest possible score / range of scores) x100
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Number of Participants Stratified by Alignment Level on IKDC Knee Evaluation Knee examination with respect to alignment (obvious varus, normal, obvious valgus) were summarized as number and percent of subjects in treatment group for Baseline and post-operative follow-up visits.
The IKDC Knee Evaluation Form was comprised of 3 domains: 1) symptoms including pain, stiffness, swelling, locking/catching, and giving way; 2) sports and daily activities; and 3) current knee function and knee function prior to knee injury.
There were 18 questions and the raw score was transformed to a 0 to 100 scale score as follows:
IKDC score = (raw score - lowest possible score / range of scores) x100
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Number of Participants Stratified by Patellar Position Level on IKDC Knee Evaluation Knee examination with respect to patella position (obvious baja, normal, obvious alta) were summarized as number and percent of subjects in treatment group for Baseline and post-operative follow-up visits.
The IKDC Knee Evaluation Form was comprised of 3 domains: 1) symptoms including pain, stiffness, swelling, locking/catching, and giving way; 2) sports and daily activities; and 3) current knee function and knee function prior to knee injury.
There were 18 questions and the raw score was transformed to a 0 to 100 scale score as follows:
IKDC score = (raw score - lowest possible score / range of scores) x100
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Number of Participants Stratified by Patella Subluxation/Dislocation Level on IKDC Knee Evaluation Knee examination with respect to patella subluxation/ dislocation (centered, subluxable, subluxed and dislocated) were summarized as number and percent of subjects in treatment group for Baseline and post-operative follow-up visits.
The IKDC Knee Evaluation Form was comprised of 3 domains: 1) symptoms including pain, stiffness, swelling, locking/catching, and giving way; 2) sports and daily activities; and 3) current knee function and knee function prior to knee injury.
There were 18 questions and the raw score was transformed to a 0 to 100 scale score as follows:
IKDC score = (raw score - lowest possible score / range of scores) x100
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in KOOS Scores From Baseline The scores of 5 subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS) (i.e., pain, other symptoms, function in daily living [ADL], function in sport and recreation [Sport/Rec], and knee-related Quality of Life [QoL]) change from Baseline were summarized descriptively by treatment group. An ANCOVA model was used to compare the differences in the devices for change from Baseline in the KOOS subscale score at each of the scheduled post-operative visits.
Each subscale response was based on a 5-point Likert system with each response score ranging from 0 (no problems) to 4 (extreme problems). A score of 100 indicated no problems and a score of 0 indicated extreme problems.
The KOOS calculations were calculated as follows:
Individual KOOS subscale scores = 100 - (mean of the observed items within the subscale x100) / 4
Change from Baseline in KOOS at Week (x) or Day (x) = KOOS at Week (x) or Day (x) - KOOS at Baseline
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in Visual Analog Scale (VAS) Scores From Baseline The VAS knee pain scores were assessed at Baseline, post-operative visits (Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET) and change from Baseline were summarized descriptively by treatment group. An ANCOVA model was used to compare the differences in the devices for change from Baseline in the VAS knee pain score at each of the scheduled post-operative visits. The model had change in VAS knee pain as the response variable and treatment, Baseline VAS knee pain, site, treatment-by-site interaction, lesion-grade, and lesion-grade interaction as independent variables.
Scores ranged from 0 to 100 with pain intensity measured as none, mild, moderate, or severe:
No pain (0-4) Mild pain (5-44) Moderate pain (45-74) Severe pain (75-100)
VAS scores were calculated as:
Change in VAS knee pain score from Baseline at Week (x) or Day (x) = VAS knee pain at Week (x) or Day (x) - VAS knee pain at Baseline
Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in 12-Item Short Form Survey (SF-12) Scores From Baseline - Physical Component Summary (PCS) Score SF-12 PCS scores at Baseline, post-operative visits (Weeks 6, 12, 24, 36, 52 and 104) and changes from Baseline were summarized descriptively by treatment group. The SF-12 health survey categories included: physical functioning, role functioning physical, bodily pain, general health, vitality, social functioning, role functioning emotional, and mental health. An ANCOVA model was used to compare the difference in the devices for change from Baseline in the SF-12 PCS scores at each of the scheduled post-operative visits. The model had change in SF-12 PCS score as the response variable and treatment, Baseline SF-12 PCS score, site, treatment-by-site interaction, lesion-grade and treatment-by-lesion grade interaction as independent variables.
Results were expressed as the PCS. Scores could range from 0 (the worst) to 100 (the best).
SF-12 scores for PCS were calculated as:
Change in SF-12 PCS score from Baseline at Week (x) = PCS score at Week (x) - PCS score at Baseline
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in SF-12 Scores From Baseline - Mental Component Summary (MCS) Score SF-12 MCS scores at Baseline, post-operative visits (Weeks 6, 12, 24, 36, 52, and 104) and changes from Baseline were summarized descriptively by treatment group. The SF-12 health survey categories included: physical functioning, role functioning physical, bodily pain, general health, vitality, social functioning, role functioning emotional, and mental health. An ANCOVA model was used to compare the difference in the devices for change from Baseline in the SF-12 MCS scores at each of the scheduled post-operative visits. The model had change in SF-12 MCS score as the response variable and treatment, Baseline SF-12 MCS score, site, treatment-by-site interaction, lesion-grade and treatment-by-lesion grade interaction as independent variables.
Results were expressed as the MCS. Scores could range from 0 (the worst) to 100 (the best).
SF-12 scores for MCS were calculated as:
Change in SF-12 MCS score from Baseline at Week (x) = MCS score at Week (x) - MCS score at Baseline
Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in EuroQoL 5 Dimensions, 5 Level Scale (EQ-5D-5L) Scores From Baseline (EQ-5D-5L Summary Total Score) The EQ-5D-5L and EQ-VAS surveys were assessed at the specified time points. The EQ-5D-5L score was composed of 5 dimensions to assess mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on participant's responses. Each individual category calculated a score of between -1 and +1. A score of -1 showed the worst improvement and a score of +1 showed the most improvement.
Summary total scores for EQ-5D-5L were calculated as:
Change in EQ-5D-5L score from Baseline at Week (x) or Day (x) = EQ-5D-5L score at Week (x) or Day (x) - EQ-5D-5L score at Baseline
Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Change in EQ-5D-5L Scores From Baseline (EQ-VAS Summary Total Score) The EQ-5D-5L and EQ-VAS surveys were assessed at the specified time points. The EQ-5D-5L score was composed of 5 dimensions to assess mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on participant's responses.
The EQ-VAS score ranged from 0 to 100 with higher scores representing better health and lower scores representing worse health.
Summary total scores for EQ-VAS were calculated as:
Change in EQ-VAS score from Baseline at Week (x) or Day (x) = EQ-VAS score at Week (x) or Day (x) - EQ-VAS score at Baseline
Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET
Secondary Subject Satisfaction Postoperatively at Weeks 52 and 104 Subjects were questioned regarding their satisfaction with study treatment for knee pain. Postop Weeks 52 and 104/ET
Secondary Magnetic Resonance Imaging (MRI) and International Cartilage Repair Society (ICRS) Chondral Lesion Assessments MRIs were obtained post-operatively at Day 10, obtained during the time period of Day 10 through Week 52, and again obtained during the time period of Week 52 through Week 104/ET). The images were evaluated using ICRS assessments of chondral lesions to determine the percentage of change in cartilage lesions over time post-operatively.
ICRS partial-thickness chondral lesion assessment scores:
Low-grade defect = less than 50% High-grade defect = 50% to 99%
Postop Day 10, Day 10 to Week 52, Week 52 to Week 104/ET