Prospective Trial of Arthroscopic Meniscectomy for Degenerative Meniscus Tears

NCT ID: NCT01931735

Last Updated: 2018-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-01
• Study Completion Date: 2018-01-31

Brief 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.

Conditions

Meniscus Tear

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Randomized Meniscectomy

This group will have a partial meniscectomy

Group Type: EXPERIMENTAL

Randomized Meniscectomy

Intervention Type: PROCEDURE

Arthroscopic meniscectomy

Randomized Lavage

This group will have arthroscopy and lavage

Group Type: ACTIVE_COMPARATOR

Randomized Lavage

Intervention Type: PROCEDURE

Arthroscopic Lavage

Standard of Care Meniscectomy Pre-Amend

Pre-Amendment: surgeons determined standard of care option, meniscectomy, best benefited the patient. Therefore, the patient was not randomized.

Group Type: OTHER

Standard of Care Meniscectomy Pre-Amend

Intervention Type: PROCEDURE

Arthroscopic meniscectomy

Standard of Care Meniscectomy Post-Amend

Post Amendment: patients received a meniscectomy as a standard of care and were observed for 24-months post-operative.

Group Type: OTHER

Standard of Care Meniscectomy Post-Amend

Intervention Type: PROCEDURE

Arthroscopic meniscectomy

Interventions

Randomized Meniscectomy

Arthroscopic meniscectomy

Intervention Type: PROCEDURE

Randomized Lavage

Arthroscopic Lavage

Intervention Type: PROCEDURE

Standard of Care Meniscectomy Pre-Amend

Arthroscopic meniscectomy

Intervention Type: PROCEDURE

Standard of Care Meniscectomy Post-Amend

Arthroscopic meniscectomy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Veteran
• Age between 45 and 70 years
• Degenerative meniscus tear as seen on standard clinical MRI scan
• Complaint of "mechanical symptoms" which would include popping, catching, or locking of the knee
• Persistent symptoms for a minimum of three months despite conservative management
• Patient is enrolled for arthroscopic meniscectomy
• Subject agrees to the study follow-up schedule and signs informed consent.

Exclusion Criteria

• Radiographic osteoarthritis of the knee in any compartment greater than KL grade 2
• Prior knee arthroscopy within two years of study enrollment
• Unable to have an MRI scan
• Does not agree to participate

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas J. Giori, MD PhD

Role: PRINCIPAL_INVESTIGATOR

VA Palo Alto Health Care System, Palo Alto, CA

Locations

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

Countries

United States

References

Edd SN, Giori NJ, Andriacchi TP. The role of inflammation in the initiation of osteoarthritis after meniscal damage. J Biomech. 2015 Jun 1;48(8):1420-6. doi: 10.1016/j.jbiomech.2015.02.035. Epub 2015 Feb 26.

Reference Type: BACKGROUND

PMID: 25798759 (View on PubMed)

Edd SN, Netravali NA, Favre J, Giori NJ, Andriacchi TP. Alterations in knee kinematics after partial medial meniscectomy are activity dependent. Am J Sports Med. 2015 Jun;43(6):1399-407. doi: 10.1177/0363546515577360. Epub 2015 Mar 31.

Reference Type: BACKGROUND

PMID: 25828080 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1I01RX000924-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E0924-R

Identifier Type: -

Identifier Source: org_study_id