Clinical trial NCT03112200: Subchondroplasty® Knee RCT
Official title: A Randomized Controlled Trial of the Subchondroplasty® Procedure With Arthroscopy Versus Arthroscopy Alone for Treatment of Bone Marrow Lesions in the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bone Marrow Edema
Knee Pain Chronic
Knee Osteoarthritis
Osteoarthritis, Knee
Osteoarthritis
Keywords: Subchondroplasty
Arthroscopy
Bone Substitute Material
Subchondral Bone Defect
AccuFill
Bone Marrow Lesion
Knee Replacement
Knee Replacement Alternative
Lead sponsor: Zimmer Biomet
Sponsor class: INDUSTRY
Collaborators: name: MedNet Solutions
name: Medical Metrics Diagnostics, Inc
First posted: 2017-04-13
Enrollment: 134
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A stratified blocked randomization will be used to assign subjects to either Subchondroplasty with arthroscopy or to arthroscopy alone in a 2:1 ratio. Individual sets of blocks will be determined within study site and lesion polarity status (unipolar vs. bipolar).
Primary purpose: TREATMENT

Brief summary: This is a multi-center, prospective, single-blinded, two-arm study, randomized to include approximately 134 subjects treated with Subchondroplasty (SCP) + Arthroscopy and 67 subjects with arthroscopy alone.

The primary objective of this study is to demonstrate superiority of Subchondroplasty with arthroscopy compared to arthroscopy alone for treatment of Bone Marrow Lesions (BMLs) in the knee.

Detailed description: This is a multicenter, prospective, single-blinded, two-arm, randomized study. Enrolled subjects will have a single Bone Marrow Lesion of the tibia, single BML of the femur, or adjoining Bone Marrow Lesions of tibia and femur. Subjects will also be surgical candidates for knee arthroscopy due to mechanical symptoms, meniscus tear, loose body and/or synovitis.

A stratified blocked randomization will be used to assign subjects to either Subchondroplasty with arthroscopy or to arthroscopy alone in a 2:1 ratio. Individual sets of blocks will be determined within study site and lesion polarity status (unipolar vs. bipolar).

Subjects will be enrolled within 60 days prior to surgery and take part in follow-up visits for two years following surgery. A preoperative visit will occur at the time of enrollment. Follow-up visits were to initially occur at the study site at 6 weeks, 3 months, 6 months, 12 months, and 24 months post-surgery. Telephone follow-up interviews to be be performed at 9 and 18 months post-surgery. Target enrollment was 201 subjects, to include 134 subjects in the treatment group (Subchondroplasty + Arthroscopy) and 67 subjects in the control group (Arthroscopy alone).

As of October 2020, follow-up has been amended to be completed remotely, where all visits can be performed electronically and/or via telephone.

Subjects will complete the study at the 24 month follow-up visit. For the purposes of this protocol, a revision will be defined as any partial or total joint arthroplasty or any bone fixation, bone grafting or bone substitute procedure in the same compartment in the study knee.

Eligibility criteria: Inclusion Criteria:

* Candidates must meet ALL of the following:

  1. Voluntary signature of the Institutional Review Board/Research Ethics Board approved Informed Consent,
  2. Male or female subjects between the ages of 30 to 75 years,
  3. Body Mass Index ≤ 40 (BMI=kg/m2),
  4. Has experienced pain in study knee for at least 3 months,
  5. Kellgren-Lawrence grade 1-3 Osteoarthritis, as reviewed on preoperative XR imaging, in the study knee,
  6. BML is confirmed on T2 weighted or Proton Density MR Imaging by presence of white signal,
  7. Single BML of tibia, single BML of femur, or adjoining BML's of tibia \& femur, in the same compartment, extending to the articular surface of the joint,
  8. Surgical candidate for knee arthroscopy due to mechanical symptoms, meniscus tear, loose body and/or synovitis,
  9. Must record a response, at the preoperative study visit, of moderate to extreme pain for any one of the KOOS Pain Scale questions, P2 through P9,
  10. Index knee alignment is defined radiographically as one of the following: Neutral, ≤ 6° mechanical varus, or ≤ 6° mechanical valgus,
  11. Ligaments in the study knee are stable,
  12. The contralateral (non-study) knee is stable and functional,
  13. Is refractory to conservative non-surgical management

      1. having failed 2 or more of the following: hyaluronic acid injection, corticosteroid injection, NSAIDs, physical therapy, bracing, activity modification, or minimal surgical intervention (e.g., arthroscopy, debridement/chondroplasty, and/or loose body removal)
      2. and is ≥ 3 months from the start of treatment,
  14. Must be physically and mentally willing and able, in the Investigator's opinion at the time of enrollment, to be compliant with the protocol - including all follow-up visits, survey completion, weight-bearing restrictions, and post-operative rehabilitation.

Exclusion Criteria:

* Candidates will be excluded if they meet ANY of the following:

  1. BML caused by acute trauma less than 3 months prior to enrollment,
  2. Clinical and/or radiographic disease diagnosis of the index knee that includes any of the following:

     1. Kellgren-Lawrence Grade 4 Osteoarthritis with complete loss of joint space (bone-on-bone) or subchondral bone collapse,
     2. Rheumatoid arthritis, or history of septic or reactive arthritis,
     3. Gout or a history of gout or pseudogout in the affected knee,
     4. Has more than two clinically relevant BMLs in the index knee,
     5. Osteochondritis dissecans of the knee with significant bone loss,
     6. Collapse of subchondral bone,
     7. Clinically relevant BML located at ACL/PCL insertion,
     8. MRI evidence of frank ligament instability,
  3. Passive knee flexion \< 110° or flexion contracture \>30°,
  4. History of systemic diseases which could contribute to secondary arthropathies (e.g., sickle cell disease, hemochromatosis, or autoimmune disease),
  5. Has a neuromuscular, neurosensory, or musculoskeletal deficiency that limits the ability to perform objective functional assessment of either knee,
  6. If diabetic, blood glucose over 200 mg/dL at time of enrollment,
  7. Current daily tobacco or high nicotine product user or \< 3 months from nicotine cessation,
  8. Presents a high surgical risk due to unstable cardiac and/or pulmonary disease,
  9. Has HIV or other immunodeficient state including subjects on immunosuppressant therapies, or has significant illness (metastasis of any type) that decreases the probability of survival to the 2 year endpoint,
  10. Is at substantial risk for the need of organ transplantation, such as renal insufficiency,
  11. Is pregnant or breast-feeding at the time of surgery,
  12. Has a history of any invasive malignancy (except non-melanoma skin cancer), unless treated with curative intent and with no clinical signs or symptoms of the malignancy for 5 years,
  13. Has primary bone tumor in the knee area,
  14. Anticipates having a lower extremity surgery other than the investigational surgery during the course of the study,
  15. Is participating concurrently in another clinical trial, or has participated in a clinical trial within 30 days of surgery,
  16. Is receiving prescription pain medication other than NSAIDs or acetaminophen for conditions unrelated to the index knee condition, chronic use of anticoagulants, or taking corticosteroids,
  17. Active joint infection or history of chronic joint infection at the surgical site,
  18. Prior total meniscectomy of index knee,
  19. Has primarily patellofemoral symptoms,
  20. Is indicated for concomitant procedures (i.e., microfracture, subchondral drilling, cartilage allograft, ligament or tendon repair, distal realignment/osteotomy, root repair) in the index knee, with the exception of incidental loose body removal, debridement, synovectomy, osteophyte removal in locations other than adjacent to BMLs, and/or partial meniscectomy,
  21. Has contraindications for Magnetic Resonance Imaging (MRI),
  22. Is receiving worker's compensation or is currently involved in litigation relating to the index knee,
  23. Has a history of substance abuse.

Primary outcomes:
measure: Composite Clinical Success
timeFrame: Superiority will be statistically tested at month 12 at p<0.01
Secondary outcomes:
measure: Change from baseline KOOS subscale scores at 12 Months
timeFrame: 12 months post-surgery
measure: Change from baseline Numeric Pain Score at 12 Months
timeFrame: 12 months post-surgery
measure: Change from baseline EQ-5D score at 12 Months
timeFrame: 12 months post-surgery
measure: Change from baseline Global Satisfaction score at 12 Months
timeFrame: 12 months post-surgery
measure: Change from baseline x-rays to 12 Months
timeFrame: 12 months post-surgery
measure: MRI analysis
timeFrame: 12 months post-surgery
measure: Incidence of post-operative complications and adverse events
timeFrame: 12 months post-surgery
measure: Time to resolution of post-operative complications and adverse events
timeFrame: 12 months post-surgery
measure: Incidence of joint injections
timeFrame: 12 months post-surgery
measure: Time to joint injections
timeFrame: 12 months post-surgery
measure: Incidence of re-operations and revisions
timeFrame: 12 months post-surgery
measure: Time to re-operations and revisions
timeFrame: 12 months post-surgery
measure: Healthcare utilization
timeFrame: 12 months post-surgery
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: CORE Orthopaedic Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health System
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Foundation for Orthopaedic Research and Education
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Timonium
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Albuquerque
country: United States
facility: New Mexico Orthopaedic Fellowship Foundation
state: New Mexico
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Greenville
country: United States
facility: Hawkins Foundation
state: South Carolina
city: Austin
country: United States
facility: Orthopedic Associates of Central Texas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Hamilton
country: Canada
facility: Research St. Joseph's - Hamilton
state: Ontario
Study officials:
affiliation: University of Colorado, Denver
name: Jason Dragoo, MD
role: PRINCIPAL_INVESTIGATOR
References: