ACT: Mechanical vs. Radiofrequency-Based Debridement in the Treatment of Articular Cartilage Lesions

• Sponsor: Smith & Nephew, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01803880
• Collaborator: (none)
• Enrollment: 148
• Locations: 7
• Arms: 2
• Actual Duration (Months): 52.4
• Patients Per Site: 21.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chondral Lesion Plus Partial Medial Meniscectomy	Device: Mechanical Debridement; Device: RF-Based Debridement	N/A

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double Blinded, Multicenter, Randomized, Controlled Trial to Evaluate Mechanical Debridement vs. Radiofrequency-Based Debridement in the Treatment of Articular Cartilage Lesions
• Actual Study Start Date: Mar 8, 2013
• Actual Primary Completion Date: May 4, 2017
• Actual Study Completion Date: Jul 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Mechanical Debridement Mechanical shaver removes areas of damaged tissue	Device: Mechanical Debridement; mechanical shaver that removes areas of damaged tissue; Other Names: Mechanical Shaver
Active Comparator: RF-based Debridement Electrical energy removes areas of damaged tissue (Coblation®)	Device: RF-Based Debridement; Electrical energy that removes areas of damaged tissue (Coblation®); Other Names: Paragon T2 ICW, FLOW 50 wand

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Knee and Osteoarthritis Outcomes Scores (KOOS) at Week 52 Post-operative [Postop Week 52]

   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)

Secondary Outcome Measures

1. Change in International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form Scores From Baseline. [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/Early Termination (ET)]

   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.

2. Number of Participants Stratified by Generalized Laxity Level on IKDC Knee Evaluation [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

3. Number of Participants Stratified by Alignment Level on IKDC Knee Evaluation [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

4. Number of Participants Stratified by Patellar Position Level on IKDC Knee Evaluation [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

5. Number of Participants Stratified by Patella Subluxation/Dislocation Level on IKDC Knee Evaluation [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

6. Change in KOOS Scores From Baseline [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

7. Change in Visual Analog Scale (VAS) Scores From Baseline [Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

8. Change in 12-Item Short Form Survey (SF-12) Scores From Baseline - Physical Component Summary (PCS) Score [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

9. Change in SF-12 Scores From Baseline - Mental Component Summary (MCS) Score [Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET]

   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

10. Change in EuroQoL 5 Dimensions, 5 Level Scale (EQ-5D-5L) Scores From Baseline (EQ-5D-5L Summary Total Score) [Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET]

    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

11. Change in EQ-5D-5L Scores From Baseline (EQ-VAS Summary Total Score) [Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET]

    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

12. Subject Satisfaction Postoperatively at Weeks 52 and 104 [Postop Weeks 52 and 104/ET]

    Subjects were questioned regarding their satisfaction with study treatment for knee pain.

13. Magnetic Resonance Imaging (MRI) and International Cartilage Repair Society (ICRS) Chondral Lesion Assessments [Postop Day 10, Day 10 to Week 52, Week 52 to Week 104/ET]

    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%

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

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

4. < 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:

4. active joint infections

5. 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

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

7. metastatic and/or neoplastic disease

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

9. coagulation disorder or patient is receiving anti-coagulants

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

11. 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)

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

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

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

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

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

17. fractures, osteocysts or osteolysis

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

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

20. symptomatic tear of the lateral meniscus

21. avascular necrosis

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

23. previous total or partial meniscectomy

24. requires reconstruction or replacement of medial or lateral meniscus

25. knee instability, malalignment, or patellar tracking dysfunction

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

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

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

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

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

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

32. 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

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

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

35. Cardiac pacemaker or other electronic implant(s)

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

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

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

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

40. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tucson Orthopaedic Institute	Tucson	Arizona	United States	85712
2	Andrews Research and Education Foundation, Inc.	Gulf Breeze	Florida	United States	32561
3	Orthopaedic Research Foundation, Inc.	Greenwood	Indiana	United States	46143
4	Ohio State University	Columbus	Ohio	United States	43221
5	University Orthopedics Center	State College	Pennsylvania	United States	16801
6	Methodist Center For Orthopedic Surgery	Houston	Texas	United States	77070
7	Basin Orthopedic Surgical Specialists	Odessa	Texas	United States	79761

Sponsors and Collaborators

• Smith & Nephew, Inc.

Investigators

• Principal Investigator: Jack Farr II, MD, Orthopaedic Research Foundation, Inc.
• Study Chair: Beate Hansen, MD, PhD, Vice President, Global Clinical Strategy

Study Documents (Full-Text)

• Study Protocol - Oct 27, 2016
• Statistical Analysis Plan - Mar 10, 2017

More Information

Publications

None provided.

• Responsible Party: Smith & Nephew, Inc.
• ClinicalTrials.gov Identifier: NCT01803880
• Other Study ID Numbers: SM-2012-02
• First Posted: Mar 4, 2013
• Last Update Posted: Mar 28, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Smith & Nephew, Inc.: Articular cartilage; Cartilage lesion; Cartilage defect; Radiofrequency; Debridement; Cartilage; Coblation; Knee; Meniscus; Meniscectomy; MR imaging; Mechanical debridement; Mechanical shaver; Torn meniscus; Arthroscopic knee surgery; Damaged cartilage

Study Results

Participant Flow

Recruitment Details	There were 148 subjects who initially signed a consent form, although 72 subjects withdrew consent prior to starting the study. This resulted in only 76 subjects actually starting the study and proceeding with study treatment.
Pre-assignment Detail	Part I required all qualified investigators to perform 1 to 3 procedures using the study devices for the purpose of minimizing variability with the recommended directions for use established in the instructions for use. Part I subjects were to be included in the safety population only.

Arm/Group Title	Part I	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Part I: All Investigators were required to perform 1 to 3 procedures using the study device to minimize variability relating to the technique recommended in the IFU. These subjects were followed per protocol and analyzed for safety findings only.	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Period Title: Overall Study
STARTED	19	28	29
COMPLETED	13	18	14
NOT COMPLETED	6	10	15

Baseline Characteristics

Arm/Group Title	Part I	Part II: RF-based Debridement	Part II: Mechanical Debridement	Total
Arm/Group Description	Part I: All Investigators were required to perform 1 to 3 procedures using the study device to minimize variability relating to the technique recommended in the IFU. These subjects were followed per protocol and analyzed for safety findings only.	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.	Total of all reporting groups
Overall Participants	19	28	29	76
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.1 (8.15)	59.9 (7.22)	58.0 (9.76)	57.7 (8.68)
Age, Customized (Count of Participants)
<40 years	1 5.3%	0 0%	1 3.4%	2 2.6%
≥40 years	18 94.7%	28 100%	28 96.6%	74 97.4%
Sex: Female, Male (Count of Participants)
Female	8 42.1%	13 46.4%	11 37.9%	32 42.1%
Male	11 57.9%	15 53.6%	18 62.1%	44 57.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 7.1%	4 13.8%	6 7.9%
Not Hispanic or Latino	19 100%	26 92.9%	25 86.2%	70 92.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	17 89.5%	27 96.4%	29 100%	73 96.1%
Black or African American	2 10.5%	0 0%	0 0%	2 2.6%
Other	0 0%	1 3.6%	0 0%	1 1.3%
Hispanic	0 0%	1 3.6%	0 0%	1 1.3%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.4 (3.02)	29.9 (3.41)	29.0 (4.02)	29.2 (3.57)
Total pre-debridement lesion size (Count of Participants)
≤2 cm^2	13 68.4%	19 67.9%	23 79.3%	55 72.4%
>2-4 cm^2	4 21.1%	9 32.1%	6 20.7%	19 25%
Missing	2 10.5%	0 0%	0 0%	2 2.6%
Duration (days) since onset of symptoms for index knee (Count of Participants)
Acute: ≤30 days	0 0%	3 10.7%	2 6.9%	5 6.6%
Subacute: 31 days - 6 months	8 42.1%	16 57.1%	20 69%	44 57.9%
Chronic: >6 months	11 57.9%	9 32.1%	6 20.7%	26 34.2%
Missing	0 0%	0 0%	1 3.4%	1 1.3%
Knee Alignment (Count of Participants)
Varus malalignment	1 5.3%	1 3.6%	0 0%	2 2.6%
Valgus malalignment	0 0%	1 3.6%	0 0%	1 1.3%
Normal	18 94.7%	26 92.9%	29 100%	73 96.1%
Narrowest width of meniscal rim post-operatively (radial measurement of meniscus post resection) (Count of Participants)
0 - 3º	5 26.3%	10 35.7%	7 24.1%	22 28.9%
>3º	12 63.2%	18 64.3%	22 75.9%	52 68.4%
Missing	2 10.5%	0 0%	0 0%	2 2.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Knee and Osteoarthritis Outcomes Scores (KOOS) at Week 52 Post-operative
Description	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)
Time Frame	Postop Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	28
Least Squares Mean (Standard Error) [score on a scale]	31.94 (3.991)	39.36 (4.210)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part II: RF-based Debridement, Part II: Mechanical Debridement
	Comments	An ANCOVA model was used to compare the difference in the devices for change from Baseline in the KOOS at Week 52. KOOS was derived as the average of five subscale scores. LOCF imputation was considered for missing value. One-sided 97.5% confidence interval (CI) for treatment difference (Study-Control) was to be used for determining non-inferiority/superiority of the study device.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority Margin = 10 points. Non-inferiority of study device was concluded if lower limit of one-sided 97.5% CI for treatment difference <10. Superiority of study device was established if LS means of treatment difference and lower limit of one-sided 97.5% CI for treatment difference ≤0.
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	All unscheduled visits were to be included and nominal visits were to be applied using analysis visit windows. Both the assigned analysis visits and the site reported nominal visits were provided in the subject data listings.
	Method	ANCOVA
	Comments	Due to early termination, all inferential analysis was interpreted as descriptive and carried out in an exploratory manner.
Method of Estimation	Estimation Parameter	One-sided 97.5% confidence interval (CI)
	Estimated Value	-7.42
	Confidence Interval	(1-Sided) 97.5%; -19.29 to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.137
	Estimation Comments

2. Secondary Outcome

Title	Change in International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form Scores From Baseline.
Description	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.
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/Early Termination (ET)

Outcome Measure Data

Analysis Population Description

Not all participants completed the IKDC score questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
IKDC Summary Total Scores (Baseline)	39.4 (14.56)	37.3 (14.40)
Week 6	60.7 (15.42)	64.4 (16.39)
Week 6 (Change from Baseline)	21.0 (13.30)	27.0 (22.17)
Week 12	69.8 (20.63)	70.3 (20.24)
Week 12 (Change from Baseline)	30.6 (19.57)	33.1 (20.55)
Week 24	72.9 (21.21)	70.2 (17.31)
Week 24 (Change from Baseline)	33.4 (17.71)	32.7 (21.07)
Week 36	70.2 (25.61)	78.8 (15.50)
Week 36 (Change from Baseline)	30.6 (22.05)	41.1 (18.25)
Week 52	75.7 (25.61)	80.4 (20.26)
Week 52 (Change from Baseline)	30.6 (22.05)	45.3 (21.20)
Week 104/ET	77.2 (20.63)	80.0 (21.66)
Week 104/ET (Change from Baseline)	36.8 (21.84)	45.8 (20.46)

3. Secondary Outcome

Title	Number of Participants Stratified by Generalized Laxity Level on IKDC Knee Evaluation
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the IKDC score questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Tight	0 0%	1 3.6%
Normal	28 147.4%	28 100%
Lax	0 0%	0 0%
Tight	0 0%	0 0%
Normal	26 136.8%	26 92.9%
Lax	0 0%	0 0%
Tight	0 0%	0 0%
Normal	25 131.6%	26 92.9%
Lax	0 0%	0 0%
Tight	0 0%	0 0%
Normal	24 126.3%	23 82.1%
Lax	0 0%	0 0%
Tight	0 0%	1 3.6%
Normal	19 100%	21 75%
Lax	0 0%	0 0%
Tight	0 0%	0 0%
Normal	20 105.3%	20 71.4%
Lax	0 0%	0 0%
Tight	0 0%	0 0%
Normal	20 105.3%	15 53.6%
Lax	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants Stratified by Alignment Level on IKDC Knee Evaluation
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the IKDC score questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Obvious Varus	1 5.3%	0 0%
Normal	26 136.8%	29 103.6%
Obvious Valgus	0 0%	0 0%
Obvious Varus	1 5.3%	0 0%
Normal	25 131.6%	26 92.9%
Obvious Valgus	0 0%	0 0%
Obvious Varus	0 0%	1 3.6%
Normal	25 131.6%	25 89.3%
Obvious Valgus	0 0%	0 0%
Obvious Varus	0 0%	0 0%
Normal	24 126.3%	23 82.1%
Obvious Valgus	0 0%	0 0%
Obvious Varus	0 0%	1 3.6%
Normal	19 100%	21 75%
Obvious Valgus	0 0%	0 0%
Obvious Varus	1 5.3%	0 0%
Normal	19 100%	20 71.4%
Obvious Valgus	0 0%	0 0%
Obvious Varus	1 5.3%	1 3.6%
Normal	19 100%	14 50%
Obvious Valgus	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants Stratified by Patellar Position Level on IKDC Knee Evaluation
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the IKDC score questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Obvious Baja	0 0%	0 0%
Normal	28 147.4%	29 103.6%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	26 136.8%	26 92.9%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	25 131.6%	26 92.9%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	24 126.3%	23 82.1%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	19 100%	22 78.6%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	20 105.3%	20 71.4%
Obvious Alta	0 0%	0 0%
Obvious Baja	0 0%	0 0%
Normal	20 105.3%	15 53.6%
Obvious Alta	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants Stratified by Patella Subluxation/Dislocation Level on IKDC Knee Evaluation
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the IKDC score questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Centered	28 147.4%	29 103.6%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	26 136.8%	25 89.3%
Subluxable	0 0%	1 3.6%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	25 131.6%	26 92.9%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	24 126.3%	23 82.1%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	19 100%	21 75%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	20 105.3%	20 71.4%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%
Centered	20 105.3%	15 53.6%
Subluxable	0 0%	0 0%
Subluxed	0 0%	0 0%
Dislocated	0 0%	0 0%

7. Secondary Outcome

Title	Change in KOOS Scores From Baseline
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the KOOS questionnaires.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Pain - Baseline	46.2 (17.26)	50.6 (13.10)
Pain - Week 6	70.9 (19.62)	80.4 (14.90)
Pain - Week 6 (Change from Baseline)	25.3 (16.92)	29.9 (19.66)
Pain - Week 12	80.6 (20.05)	82.3 (17.23)
Pain - Week 12 (Change from Baseline)	35.8 (21.92)	30.3 (19.83)
Pain - Week 24	78.5 (22.15)	80.4 (15.39)
Pain - Week 24 (Change from Baseline)	32.5 (21.91)	29.1 (18.37)
Pain - Week 36	78.7 (25.98)	89.0 (9.55)
Pain - Week 36 (Change from Baseline)	29.6 (25.92)	36.8 (12.94)
Pain - Week 52	81.5 (24.91)	87.6 (18.30)
Pain - Week 52 (Change from Baseline)	35.8 (21.98)	38.2 (18.79)
Pain - Week 104/ET	88.3 (15.18)	88.5 (17.47)
Pain - Week 104/ET (Change from Baseline)	38.9 (21.50)	39.3 (15.17)
Other Symptoms - Baseline	58.4 (20.72)	54.7 (16.70)
Other Symptoms - Week 6	73.5 (17.64)	75.7 (18.48)
Other Symptoms - Week 6 (Change from Baseline)	16.0 (20.76)	20.6 (22.70)
Other Symptoms - Week 12	81.3 (19.73)	83.1 (15.14)
Other Symptoms - Week 12 (Change from Baseline)	25.0 (25.63)	28.3 (20.92)
Other Symptoms - Week 24	79.8 (20.22)	80.4 (13.99)
Other Symptoms - Week 24 (Change from Baseline)	21.9 (22.55)	25.2 (18.67)
Other Symptoms - Week 36	74.1 (23.17)	87.7 (10.61)
Other Symptoms - Week 36 (Change from Baseline)	17.0 (24.90)	31.7 (17.26)
Other Symptoms - Week 52	78.7 (24.12)	88.0 (14.53)
Other Symptoms - Week 52 (Change from Baseline)	19.8 (26.33)	34.6 (19.15)
Other Symptoms - Week 104/ET	83.9 (17.71)	85.7 (15.57)
Other Symptoms -Week 104/ET (Change from Baseline)	24.5 (23.53)	34.8 (17.78)
ADLs - Baseline	53.5 (21.48)	57.3 (15.31)
ADLs - Week 6	76.6 (21.09)	86.2 (12.18)
ADLs - Week 6 (Change from Baseline)	23.3 (18.43)	29.6 (16.26)
ADLs - Week 12	84.1 (21.02)	85.3 (14.36)
ADLs - Week 12 (Change from Baseline)	32.0 (24.33)	27.0 (16.16)
ADLs - Week 24	84.6 (20.88)	87.9 (12.05)
ADLs - Week 24 (Change from Baseline)	31.1 (24.53)	31.0 (16.94)
ADLs - Week 36	78.7 (23.58)	91.3 (11.06)
ADLs - Week 36 (Change from Baseline)	24.3 (24.32)	32.0 (14.51)
ADLs - Week 52	83.6 (23.85)	89.2 (17.98)
ADLs - Week 52 (Change from Baseline)	30.4 (24.06)	32.3 (18.07)
ADLs - Week 104/ET	89.0 (16.72)	90.8 (13.39)
ADLs - Week 104/ET (Change from Baseline)	32.6 (24.53)	36.3 (16.67)
Sport/Rec - Baseline	29.9 (22.68)	30.2 (23.58)
Sport/Rec - Week 6	54.1 (25.87)	61.5 (24.25)
Sport/Rec - Week 6 (Change from Baseline)	23.1 (27.00)	29.4 (35.06)
Sport/Rec - Week 12	72.0 (24.66)	67.0 (25.96)
Sport/Rec - Week 12 (Change from Baseline)	42.3 (30.24)	38.2 (28.53)
Sport/Rec - Week 24	65.6 (30.59)	69.3 (22.88)
Sport/Rec - Week 24 (Change from Baseline)	34.9 (32.46)	40.4 (32.68)
Sport/Rec - Week 36	63.0 (33.02)	75.9 (24.33)
Sport/Rec - Week 36 (Change from Baseline)	32.8 (35.60)	45.2 (29.38)
Sport/Rec - Week 52	73.0 (30.28)	78.3 (25.09)
Sport/Rec - Week 52 (Change from Baseline)	41.4 (30.56)	51.5 (26.81)
Sport/Rec - Week 104/ET	76.0 (26.49)	77.8 (27.88)
Sport/Rec - Week 104/ET (Change from Baseline)	44.2 (25.90)	53.8 (29.38)
QoL - Baseline	28.8 (16.78)	28.4 (14.90)
QoL - Week 6	59.7 (21.11)	59.7 (19.79)
QoL - Week 6 (Change from Baseline)	31.0 (25.09)	31.3 (26.69)
QoL - Week 12	66.5 (24.13)	66.6 (25.55)
QoL - Week 12 (Change from Baseline)	39.0 (27.56)	37.7 (31.00)
QoL - Week 24	67.2 (26.98)	70.7 (21.02)
QoL - Week 24 (Change from Baseline)	36.2 (34.4)	41.0 (24.70)
QoL - Week 36	66.3 (32.66)	77.3 (23.82)
QoL - Week 36 (Change from Baseline)	35.9 (31.86)	47.4 (25.34)
QoL - Week 52	72.5 (28.42)	75.6 (26.59)
QoL - Week 52 (Change from Baseline)	41.9 (25.50)	47.5 (27.01)
QoL - Week 104/ET	79.1 (21.77)	76.7 (25.38)
QoL - Week 104/ET (Change from Baseline)	46.9 (25.29)	50.8 (22.89)
Average KOOS Score - Baseline	43.4 (17.82)	44.2 (13.56)
Average KOOS Score - Week 6	67.0 (19.77)	72.7 (14.47)
Average KOOS Score - Week 6 (Change from Baseline)	23.7 (18.85)	28.2 (20.86)
Average KOOS Score - Week 12	76.9 (20.81)	76.9 (18.59)
Average KOOS Score - Week 12 (Change/Baseline)	34.8 (23.84)	32.3 (21.05)
Average KOOS Score - Week 24	75.1 (22.69)	77.8 (15.70)
Average KOOS Score - Week 24 (Change/Baseline)	31.3 (23.01)	33.3 (20.17)
Average KOOS Score - Week 36	71.6 (26.41)	84.2 (14.59)
Average KOOS Score - Week 36 (Change/Baseline)	27.9 (25.78)	38.6 (16.82)
Average KOOS Score - Week 52	77.9 (25.41)	83.7 (19.66)
Average KOOS Score - Week 52 (Change/Baseline)	33.9 (23.42)	40.8 (19.97)
Average KOOS Score - Week 104/ET	83.3 (17.88)	83.9 (19.16)
Average KOOS Score - Week 104/ET (Change/Baseline)	37.4 (21.47)	43.0 (18.22)

8. Secondary Outcome

Title	Change in Visual Analog Scale (VAS) Scores From Baseline
Description	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
Time Frame	Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the VAS pain score questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Baseline	57.6 (19.68)	59.8 (16.15)
Day 10	28.7 (23.62)	17.6 (18.69)
Day 10 (Change from Baseline)	-29.0 (21.29)	-42.2 (23.77)
Week 6	17.8 (23.05)	13.8 (18.71)
Week 6 (Change from Baseline)	-38.1 (22.75)	-44.5 (19.90)
Week 12	12.6 (17.71)	15.2 (17.79)
Week 12 (Change from Baseline)	-45.8 (23.98)	-41.3 (21.18)
Week 24	15.3 (23.88)	13.9 (15.38)
Week 24 (Change from Baseline)	-42.6 (21.98)	-44.2 (18.64)
Week 36	19.1 (26.63)	7.9 (13.53)
Week 36 (Change from Baseline)	-37.5 (28.20)	-49.6 (17.18)
Week 52	11.5 (20.08)	9.3 (19.97)
Week 52 (Change from Baseline)	-45.8 (20.74)	-49.5 (24.54)
Week 104/ET	8.4 (14.22)	9.9 (20.60)
Week 104/ET (Change from Baseline)	-47.9 (25.92)	-50.7 (30.82)

9. Secondary Outcome

Title	Change in 12-Item Short Form Survey (SF-12) Scores From Baseline - Physical Component Summary (PCS) Score
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the SF-12 questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Baseline PCS	36.5 (10.65)	38.6 (9.63)
Week 6 PCS	45.1 (9.14)	46.6 (8.27)
Week 6 PCS (Change from Baseline)	8.2 (12.62)	6.7 (9.31)
Week 12 PCS	50.0 (7.87)	46.6 (8.27)
Week 12 PCS (Change from Baseline)	13.4 (13.14)	9.4 (10.49)
Week 24 PCS	48.5 (9.60)	50.2 (8.19)
Week 24 PCS (Change from Baseline)	11.1 (13.14)	11.6 (11.12)
Week 36 PCS	46.8 (11.49)	52.5 (6.98)
Week 36 PCS (Change from Baseline)	9.3 (13.81)	13.1 (10.43)
Week 52 PCS	48.9 (10.24)	52.5 (8.72)
Week 52 PCS (Change from Baseline)	11.6 (10.99)	14.6 (11.55)
Week 104/ET PCS	51.9 (6.96)	51.6 (8.35)
Week 104/ET PCS (Change from Baseline)	14.1 (11.02)	15.3 (11.42)

10. Secondary Outcome

Title	Change in SF-12 Scores From Baseline - Mental Component Summary (MCS) Score
Description	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
Time Frame	Baseline, Postop Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the SF-12 questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
Baseline MCS	55.9 (9.98)	55.1 (9.52)
Week 6 MCS	55.1 (8.44)	57.5 (9.63)
Week 6 MCS (Change from Baseline)	-0.1 (8.87)	3.4 (8.27)
Week 12 MCS	55.6 (7.47)	55.9 (7.75)
Week 12 MCS (Change from Baseline)	0.5 (10.97)	1.2 (8.05)
Week 24 MCS	56.6 (5.32)	56.9 (8.47)
Week 24 MCS (Change from Baseline)	0.7 (10.17)	2.6 (8.32)
Week 36 MCS	55.5 (6.49)	57.1 (4.81)
Week 36 MCS (Change from Baseline)	0.1 (10.63)	1.8 (7.61)
Week 52 MCS	56.1 (7.19)	56.1 (4.90)
Week 52 MCS (Change from Baseline)	0.6 (9.46)	1.5 (10.35)
Week 104/ET MCS	56.1 (5.17)	55.7 (9.91)
Week 104/ET MCS (Change from Baseline)	-0.4 (10.84)	0.1 (10.54)

11. Secondary Outcome

Title	Change in EuroQoL 5 Dimensions, 5 Level Scale (EQ-5D-5L) Scores From Baseline (EQ-5D-5L Summary Total Score)
Description	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
Time Frame	Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the EQ-5D-5L questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
EQ-5D-5L Summary Total Score (Baseline)	0.714 (0.1503)	0.745 (0.910)
Day 10	0.738 (0.1309)	0.788 (0.0967)
Day 10 (Change from Baseline)	0.024 (0.1331)	0.043 (0.1151)
Week 6	0.791 (0.1528)	0.825 (0.0999)
Week 6 (Change from Baseline)	0.083 (0.1080)	0.081 (0.1318)
Week 12	0.823 (0.1614)	0.854 (0.1145)
Week 12 (Change from Baseline)	0.116 (0.1182)	0.094 (0.1137)
Week 24	0.814 (0.1473)	0.854 (0.1047)
Week 24 (Change from Baseline)	0.100 (0.1436)	0.105 (0.1269)
Week 36	0.806 (0.1650)	0.914 (0.0895)
Week 36 (Change from Baseline)	0.096 (0.1524)	0.143 (0.0743)
Week 52	0.835 (0.1950)	0.911 (0.1267)
Week 52 (Change from Baseline)	0.135 (0.1502)	0.162 (0.1362)
Week 104/ET	0.843 (0.1290)	0.906 (0.1298)
Week 104/ET (Change from Baseline)	0.106 (0.1381)	0.167 (0.1470)

12. Secondary Outcome

Title	Change in EQ-5D-5L Scores From Baseline (EQ-VAS Summary Total Score)
Description	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
Time Frame	Baseline, Postop Day 10, Weeks 6, 12, 24, 36, 52, and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the EQ-VAS questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	28	29
EQ-VAS Summary Total Score (Baseline)	74.9 (21.70)	76.3 (17.90)
Day 10	80.7 (16.85)	88.0 (8.87)
Day 10 (Change from Baseline)	5.8 (18.42)	11.7 (16.80)
Week 6	84.0 (13.99)	89.5 (7.41)
Week 6 (Change from Baseline)	10.5 (14.82)	14.1 (17.87)
Week 12	84.6 (14.35)	90.1 (7.06)
Week 12 (Change from Baseline)	10.8 (13.11)	14.3 (18.55)
Week 24	87.3 (12.97)	88.4 (10.98)
Week 24 (Change from Baseline)	13.3 (16.09)	14.0 (16.63)
Week 36	84.7 (12.97)	91.0 (6.01)
Week 36 (Change from Baseline)	13.3 (16.09)	15.0 (17.81)
Week 52	84.1 (18.50)	90.2 (8.60)
Week 52 (Change from Baseline)	8.6 (18.55)	15.1 (17.24)
Week 104/ET	87.1 (12.96)	90.3 (11.55)
Week 104/ET (Change from Baseline)	9.2 (13.04)	14.9 (13.27)

13. Secondary Outcome

Title	Subject Satisfaction Postoperatively at Weeks 52 and 104
Description	Subjects were questioned regarding their satisfaction with study treatment for knee pain.
Time Frame	Postop Weeks 52 and 104/ET

Outcome Measure Data

Analysis Population Description

Not all participants completed the subject satisfaction questionnaire.

Arm/Group Title	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	29	29
Extremely Satisfied	0 0%	0 0%
Very Satisfied	12 63.2%	16 57.1%
Somewhat Satisfied	5 26.3%	2 7.1%
Somewhat Dissatisfied	2 10.5%	2 7.1%
Very Dissatisfied	0 0%	0 0%
Extremely Dissatisfied	0 0%	0 0%
Extremely Satisfied	0 0%	0 0%
Very Satisfied	15 78.9%	13 46.4%
Somewhat Satisfied	5 26.3%	2 7.1%
Somewhat Dissatisfied	0 0%	0 0%
Very Dissatisfied	0 0%	0 0%
Extremely Dissatisfied	0 0%	0 0%

14. Secondary Outcome

Title	Magnetic Resonance Imaging (MRI) and International Cartilage Repair Society (ICRS) Chondral Lesion Assessments
Description	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%
Time Frame	Postop Day 10, Day 10 to Week 52, Week 52 to Week 104/ET

Outcome Measure Data

Analysis Population Description

Only Baseline subjects and subjects showing a percentage change in cartilage signal were included in the imaging results.

Arm/Group Title	Part I	Part II: RF-based Debridement	Part II: Mechanical Debridement
Arm/Group Description	Part I: All Investigators were required to perform 1 to 3 procedures using the study device to minimize variability relating to the technique recommended in the IFU. These subjects were followed per protocol and analyzed for safety findings only.	Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.	Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
Measure Participants	19	28	29
Postop Day 10 (Baseline) - Percent (%) Lesion Fill	50.5 (15.5)	52.9 (16.6)	53.5 (16.8)
Day 10 to Week 52 - <50% Change in Lesion Fill	-0.3 (8.1)	-1.9 (4.4)	1.5 (6.6)
Day 10 to Week 52 - ≥50% Change in Lesion Fill	1.2 (11.1)	-3.4 (5.9)	-5.5 (10.8)
Weeks 52 to 104/ET - <50% Change in Lesion Fill	-5.2 (13.4)	2.9 (8.8)	-6.0 (11.9)
Weeks 52 to 104/ET - ≥50% Change in Lesion Fill	1.2 (14.7)	-3.4 (8.6)	3.7 (4.7)

Adverse Events

Time Frame	AEs were recorded from the time of surgery until subject completion, ET, or study termination, whichever happened first, assessed throughout the 24-month follow-up period.
Arm/Group Title	Part I		Part II: RF-based Debridement		Part II: Mechanical Debridement
Arm/Group Description	Part I: All Investigators were required to perform 1 to 3 procedures using the study device to minimize variability relating to the technique recommended in the IFU. These subjects were followed per protocol and analyzed for safety findings only.		Radiofrequency-Based Debridement was performed using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand. Both systems use a controlled RF-based plasma process (with the trademark 'COBLATION'). In this process, RF energy is used to excite the water molecules in a conductive medium to generate excited radicals within precisely focused plasma. The energized particles in the plasma have sufficient energy to break molecular bonds excising or dissolving (i.e., ablating) soft tissue at relatively low temperatures (typically 40 degrees C to 70 degrees C). The mechanism of action is a chemical process and not a function of the RF energy itself.		Mechanical debridement (i.e., mechanical shaver) was used as the control debridement for the treatment of chondral lesions.
All Cause Mortality
	Part I		Part II: RF-based Debridement		Part II: Mechanical Debridement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/28 (0%)		0/29 (0%)
Serious Adverse Events
	Part I		Part II: RF-based Debridement		Part II: Mechanical Debridement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		2/28 (7.1%)		1/29 (3.4%)
General disorders
Hernia	0/19 (0%)	0	1/28 (3.6%)	1	0/29 (0%)	0
Injury, poisoning and procedural complications
Patella fracture	0/19 (0%)	0	0/28 (0%)	0	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/19 (0%)	0	1/28 (3.6%)	1	0/29 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Papillary thyroid cancer	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Other (Not Including Serious) Adverse Events
	Part I		Part II: RF-based Debridement		Part II: Mechanical Debridement
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/19 (68.4%)		26/28 (92.9%)		19/29 (65.5%)
Gastrointestinal disorders
Vomiting	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Nausea	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Diarrhoea	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Constipation	0/19 (0%)	0	2/28 (7.1%)	2	0/29 (0%)	0
General disorders
Oedema peripheral	1/19 (5.3%)	1	1/28 (3.6%)	1	0/29 (0%)	0
Hernia Pain	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Pyrexia	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Infections and infestations
Urinary tract infection	1/19 (5.3%)	1	0/28 (0%)	0	1/29 (3.4%)	1
Pneumonia	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Cellulitis	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Injury, poisoning and procedural complications
Foot fracture	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Fall	1/19 (5.3%)	1	0/28 (0%)	0	1/29 (3.4%)	1
Ligament sprain	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Investigations
Blood pressure increased	1/19 (5.3%)	1	0/28 (0%)	0	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Spondylolisthesis	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Arthralgia	5/19 (26.3%)	10	20/28 (71.4%)	27	13/29 (44.8%)	14
Back pain	2/19 (10.5%)	2	2/28 (7.1%)	2	0/29 (0%)	0
Bursitis	2/19 (10.5%)	2	0/28 (0%)	0	0/29 (0%)	0
Joint swelling	1/19 (5.3%)	1	2/28 (7.1%)	2	2/29 (6.9%)	2
Plantar fasciitis	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Osteoarthritis	0/19 (0%)	0	2/28 (7.1%)	2	0/29 (0%)	0
Flank pain	1/19 (5.3%)	1	0/28 (0%)	0	0/29 (0%)	0
Musculoskeletal pain	0/19 (0%)	0	3/28 (10.7%)	3	2/29 (6.9%)	2
Joint effusion	2/19 (10.5%)	3	0/28 (0%)	0	0/29 (0%)	0
Pain in extremity	1/19 (5.3%)	1	2/28 (7.1%)	2	1/29 (3.4%)	1
Joint stiffness	1/19 (5.3%)	1	0/28 (0%)	0	1/29 (3.4%)	1
Nervous system disorders
VIIth nerve paralysis	0/19 (0%)	0	2/28 (7.1%)	2	0/29 (0%)	0
Psychiatric disorders
Depression	0/19 (0%)	0	2/28 (7.1%)	2	0/29 (0%)	0
Vascular disorders
Hypertension	0/19 (0%)	0	0/28 (0%)	0	2/29 (6.9%)	2
Deep vein thrombosis	1/19 (5.3%)	1	1/28 (3.6%)	1	0/29 (0%)	0

Limitations/Caveats

Due to early termination of the study, all inferential analyses were noted as descriptive and the clinical outcome results should be interpreted with caution.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Authorship and contents of publications shall be discussed between each Principal Investigator and Sponsor. Sponsor shall serve as coordinator of multi-center study disclosures and, in event of a disagreement among investigators, Sponsor shall determine resolution of any such dispute. Sponsor shall be furnished copies of any proposed multi-center publication or disclosure at least 90 days prior to the proposed date for submission for publication or disclosure.