Prospective Trial of Arthroscopic Meniscectomy for Degenerative Meniscus Tears
Condition: Meniscus Tear
Study type: Interventional

Summary: 
      Arthroscopic meniscectomy is among the most commonly performed orthopedic surgical procedures
      in the VA system. There remains substantial uncertainty, however, regarding the short term
      benefits and the long term consequences of arthroscopic meniscectomy in patients with
      degenerative meniscus tears. Of major concern is the fact that degenerative meniscus tears
      are associated with osteoarthritis, and it is known that within two years of surgery,
      arthroscopic debridement for osteoarthritis is no better than placebo in relieving pain and
      restoring function. Longer term, meniscectomy has been shown to be associated with elevated
      risk of osteoarthritis development, raising the concern that meniscectomy can actually be
      harmful. The purpose of this study is to determine whether meniscectomy in the setting of a
      degenerative meniscus tear is of any clinical value. Determining this would either justify
      the expenses associated with arthroscopic meniscectomy on a large number of patients, or
      would identify an area of significant potential cost savings.
    

Detailed description: 
      The overall goal of this project is to determine whether arthroscopic meniscectomy in
      degenerative meniscal tears is beneficial from a clinical and scientific viewpoint relative
      to a non-meniscectomy arthroscopy control. Arthroscopic meniscectomy is among the most
      commonly performed orthopedic surgical procedures in the VA system and nationally. In the
      investigators' practice at the VA Palo Alto Healthcare System over the last year, 80% of
      patients having knee arthroscopy for meniscus tears have been in the 45-70 years age group
      and 53% of these patients had degenerative meniscal tears without a large unstable flap.
      these data are comparable to arthroscopic meniscectomy data drawn in other settings. While
      meniscectomy is a common procedure there remains substantial uncertainty regarding the short
      term benefits and the long term consequences of arthroscopic meniscectomy in patients with
      degenerative meniscus tears. Of major concern is the fact that degenerative meniscus tears
      are associated with osteoarthritis, and it is known that within two years of surgery,
      arthroscopic debridement for osteoarthritis is no better than placebo in relieving pain and
      restoring function. Longer term, meniscectomy has been shown to be associated with elevated
      risk of osteoarthritis development, raising the concern that meniscectomy can actually be
      harmful. It has also been shown by the group that patients with clinically successful
      arthroscopic posterior medial meniscectomy have significant change in the rotational motion
      of the knee during walking. Rotational changes at the knee follow soft tissue damage and have
      been implicated in the causes for cartilage degeneration.

      Thus, there are critical unanswered questions regarding the clinical benefit as well as the
      scientific basis for arthroscopic meniscectomy for degenerative meniscal tear. To address
      these questions, this project will conduct a prospective, randomized, blinded, and controlled
      study of arthroscopic meniscectomy in patients between the ages of 45 and 70 with stable
      degenerative meniscus tears. In this study, the control group will be a group of patients
      having arthroscopic lavage of the joint, but no debridement of the stable degenerative
      meniscus tear. The aims will address clinical (self-reported) and scientific (functional)
      outcomes of arthroscopic meniscectomy in the time frame lasting up to two years after
      surgery.

      Aim 1: Test the clinical benefit of arthroscopic meniscectomy in the setting of a stable
      degenerative meniscus tear.

      Hypothesis 1a: There will be a significant differences in WOMAC scores between the
      meniscectomy and the non-meniscectomy/lavage groups at 12 months following surgery.

      Hypothesis 1b: The WOMAC scores of the non-meniscectomy/lavage group will not be inferior to
      the WOMAC scores of the meniscectomy group at 12 months after surgery.

      Aim 2: To test the functional effect of arthroscopic meniscectomy in the setting of a
      degenerative meniscus tear.

      Hypothesis 2: Subjects randomized to arthroscopy and meniscectomy will have greater changes
      in tibio-femoral rotation, knee adduction moment, and knee flexion moment at 12 months
      following surgery when compared to subjects randomized to arthroscopy and lavage.

      In addition to the above principal aims of the study, the investigators will also pursue
      other exploratory aims:

        1. Understand whether arthroscopic meniscectomy for degenerative tear results in
           accelerated radiographic progression of osteoarthritis (KL score) and regional cartilage
           thinning (3D MRI thickness maps) relative to a control group.

        2. Understand whether tibio-femoral position changes measured in the investigators' gait
           analysis relate to radiographic progression of osteoarthritis and regional cartilage
           thinning relative to the control group.

        3. Understand whether meniscal tears are associated with activation of the complement
           system and alteration of gene expression in the synovial lining of the knee, and whether
           elevated complement activity relates to radiographic OA progression following surgery.

        4. Understand whether serum biomarkers are affected in degenerative meniscus tears and
           whether they will relate to radiographic OA progression or MRI changes following
           surgery.

        5. Investigate whether articular cartilage matrix changes that are measured by advanced MR
           techniques such as T1rho, sodium, or diffusion MRI can be identified and related to
           radiographic OA progression or MRI changes following surgery.

      This prospective clinical trial with coordinated, multi-disciplinary approach will provide an
      important clinical and scientific assessment of arthroscopic meniscectomy. It will identify
      whether surgical treatment is efficacious, an important issue given the costs and risks of
      surgery. It will also provide new insight into incipient arthritis, yielding information that
      will impact future patient care.

      Update 12/2/2015:

      Since the grant was awarded, there has been a growing body of literature published that is
      directly applicable to the subject of the grant. Specifically, a prospective, randomized
      study was published in the New England Journal of Medicine in Dec 2013. In that study, the
      authors did what was proposed in the present study. They found that there was no benefit to
      meniscectomy in the setting of a degenerative meniscus tear in patients with minimal
      arthritis of the knee. A very similar study was published a few months before in one of the
      most important orthopedic journals that focuses on arthroscopy, the American Journal of
      Sports Medicine. That study was also a prospective randomized study and compared arthroscopic
      meniscectomy to non-operative treatment for degenerative meniscus tears. The authors of that
      study also found that arthroscopic meniscectomy for degenerative meniscus tears was of no
      benefit, this time over non-operative treatment.

      When the study was conceived and when the study was funded, there was a genuine uncertainty
      regarding the appropriate treatment for patients with minimal to no arthritis and a
      degenerative meniscus tear. With this growing body of literature, however, there is more
      clarity on this question, and from an ethical standpoint, without genuine equipoise,
      discussing treatment options and recruiting patients into the study become problematic. The
      study design was then changed to a prospective observational study of patients with meniscus
      tears undergoing arthroscopic meniscectomy. The investigators will still be collecting the
      same data as in the prior randomized trial. The data are patient reported outcome
      questionnaires, MRI's, and gait analyses at time points from preoperative to two years
      postoperative. The investigators will also be collecting tissue samples at the time of
      surgery for the evaluation of inflammatory markers.

      Since that time the investigators have reformulated hypotheses. Current aims and hypotheses
      are:

      Aim 1: Determine whether TEAR PATTERN affects PATIENT REPORTED OUTCOMES of arthroscopic
      meniscectomy Hypothesis 1: There will be greater improvement in patient reported outcomes
      (WOMET) in patients with displacable meniscus tears than non-displacable meniscus tears.

      Aim 2: Determine if STANDARD PREOPERATIVE MR IMAGING can predict PATIENT REPORTED OUTCOME
      following arthroscopic meniscectomy Hypothesis 2: Patients with MRI evident vertical tears
      involving 50% of the meniscus or patients with displaced meniscal flaps will have greater
      improvement in WOMET scores after debridement than those without these MRI findings.

      Aim 3: Determine if TEAR PATTERN (and resulting debridement) affects GAIT CHARACTERISTICS at
      the knee at 12 months post debridement Hypothesis 3: Subjects having debridement of a medial
      meniscus root tear or a tear that extends through the entire medial meniscus to the periphery
      will have greater adduction moment and tibial external rotation, and lower flexion angle
      range of motion than patients who have retention of circumferential fiber continuity or a
      lateral tear.

      Aim 4a: Determine if INFLAMMATORY MARKERS in the synovium at the time of surgery relate to
      PREOPERATIVE PAIN and PREOPERATIVE MENISCAL TEAR PATTERN.

      Hypothesis 4a: Greater inflammation in the synovium will be correlated with greater
      preoperative pain and with more severe preoperative meniscal damage.

      Aim 4b: Determine if INFLAMMATORY MARKERS in the synovium at the time of surgery relate to
      PATIENT REPORTED OUTCOME following arthroscopic meniscectomy.

      Hypothesis 4b: Greater inflammation in the synovium at the time of surgery will be related to
      greater improvement in pain at three months following surgery.

      Aim 5:Determine if PREOPERATIVE GAIT CHARACTERISTICS (knee flexion moment, knee adduction
      moment, and knee flexion angle) are related to preoperative WOMET scores Hypothesis 5: There
      will be a negative relationship between WOMET score and knee flexion moment preoperatively.

      In addition to the above aims, the investigators will continue to pursue the exploratory aims
      that were described in the grant application. These are exploratory because they relate to
      osteoarthritis progression, an outcome that may not be measurable at the one year time frame.
      The exploratory aims and hypotheses are:

      Exploratory Aim 1: Determine if TEAR PATTERN (and subsequent debridement) influences rate of
      osteoarthritis progression as measured by articular cartilage thinning at 2 years.

      Exploratory Hypothesis 1: Tear patterns that involve the meniscal root or complete disruption
      of the circumferential fibers of the meniscus will exhibit more rapid progression of
      osteoarthritis than other tear patterns.

      Exploratory Aim 2: Determine if GAIT DIFFERENCES (kinematic and kinetics) influence the rate
      of osteoarthritis progression as measured by articular cartilage thinning at 2 years.

      Exploratory Hypothesis 2: Greater adduction moment and external rotation will be related to
      greater cartilage thinning (2 years - pre operative).

      Exploratory Aim 3: Determine if INTRAOPERATIVE SYNOVIAL BIOPSY markers of inflammation are
      correlated with osteoarthritis progression.

      Exploratory Aim 4: Determine if FINDINGS FROM ADVANCED MR IMAGING (T1Rho, Sodium, Diffusion)
      are correlated with osteoarthritis progression.
    

Intervention name(s): Randomized Meniscectomy; Randomized Lavage; Standard of Care Meniscectomy Pre-Amend; Standard of Care Meniscectomy Post-Amend
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): Arthroscopic meniscectomy; Arthroscopic Lavage; Arthroscopic meniscectomy; Arthroscopic meniscectomy
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: menisci; tibial