Clinical trial NCT01230424: Effect of Steroid Injections in a Knee With Osteoarthritis
Official title: Effect of Intra-articular Steroids on Structural Progression of Knee OA: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis (OA) of the Knee
Keywords: OA
Knee arthritis
MRI
Steroid
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2010-10-29
Enrollment: 140
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A steroid (triamcinolone) 40 mg will be compared to placebo in a randomized placebo-controlled clinical trial testing the effect of this steroid versus placebo given into the study knee joint that has osteoarthritis (OA). The knee injection will be given once every 12 weeks over two years for a total of eight knee injections. How well each participant tolerates each injection and all the injections over time will be assessed. The safety of getting a knee injection every 12 weeks will be assessed by collecting reported adverse effects, knee examinations, and clinical laboratory tests. Participants will complete questionnaires, X-ray, MRIs, and bone density tests as part of this study.

Detailed description: This study was a two-year stratified and block-randomized double-blind, placebo controlled clinical trial of the effect of intra-articular triamcinolone 40 mg injectable suspension, administered every 3 months over two years (for a total of 8 doses). The randomization was stratified by the baseline radiographic severity of knee OA (Kellgren and Lawrence grade of 2 or 3) and gender. An interim analysis would have been conducted after the first half of participants has completed the trial. This interim analysis would have allowed the trial to be stopped early for either success or futility, or allow the trial to continue if neither success nor futility has been established. However, the plan for interim analysis was eliminated with the support of the DSMB because of feasibility issues for completing cartilage measurements contemporaneously and because early trial cessation would preclude analysis of informative secondary outcomes. The primary structural outcome objective in this study was cartilage volume loss; secondary structural outcomes included peri-articular bone marrow lesions (BML), tibial peri-articular bone density ratio (paBMD). The primary clinical outcome objective was the pain domain of the WOMAC© LK3.1; secondary clinical outcomes included WOMAC© LK3.1 stiffness and function scores and physical function tests.

Eligibility criteria: Inclusion Criteria:

* Female or Male, Age ≥ 45 years
* Chronic knee discomfort based on affirmative response to the question "During the past 12 months, have you had any pain, aching, or stiffness in or around your knee(s) on most days for at least one month?"
* Baseline (Month 0) Pain score \>2 on at least one of the WOMAC weight-bearing pain questions; and total weight-bearing pain score \<8
* Tibiofemoral or patellofemoral OA on posterior-anterior weight-bearing semi-flexed or lateral knee radiographs with severity equivalent to Kellgren and Lawrence grade 2 or 3
* Evidence of synovitis on ultrasound at screening
* Clinical examination confirming knee pain or discomfort referable to the knee joint
* Prepared to discontinue NSAID(s)/analgesic(s) for 2 days prior to each assessment

Exclusion Criteria:

* Prior septic (study) knee joint
* Prior reconstructive surgery in the study knee
* Prior osteonecrosis (avascular necrosis of bone)
* Chronic use of oral corticosteroids; knee intra-articular corticosteroid injection within 3 months of Month 0 (baseline) visit
* Ongoing use of doxycycline, indomethacin, glucosamine and/or chondroitin; or use of these within 2 months of Screening visit
* Evidence of other inflammatory joint disease (e.g., gout, CPPD)
* Serious medical conditions or impairments that, in the view of the investigator, would obstruct their participation in the trial such as uncontrolled diabetes, uncontrolled hypertension, opiate dependency
* Plan to permanently relocate from the region, or take an extended vacation for greater than 3 months during the trial period
* Planned arthroscopy and/or arthroplasty in the study knee.
* Any contra-indication to having an MRI
* Inability to speak or comprehend English

Primary outcomes:
measure: Change in Mean Cartilage Thickness in the Index Compartment (Compartment With the Most Damage)
timeFrame: Baseline to 2 years
measure: Change in Knee Pain Severity During the Past 48 Hours From the WOMAC LK3.1 Pain Score Questionnaire.
timeFrame: Baseline to 2 years
Secondary outcomes:
measure: Change in Volume of Peri-articular Bone Marrow Lesions Measured on Knee MRI.
timeFrame: Baseline to 2 years.
measure: Change in Effusion Volume Measured on Knee MRI.
timeFrame: Baseline to 2 years
measure: Change in Area of Denudation Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
timeFrame: Baseline to 2 years
measure: Change in Volumetric Cartilage Damage Index (CDI) Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
timeFrame: Baseline to 2 years
measure: Change in Function Severity During the Past 48 Hours From the WOMAC LK3.1 Function Score Questionnaire.
timeFrame: Baseline to 2 years
measure: Change in Knee Stiffness During the Past 48 Hours From the WOMAC LK3.1 Stiffness Score Questionnaire.
timeFrame: Baseline to 2 years
measure: Change in Patient's Global Assessment (Visual Analogue Scale).
timeFrame: Baseline to 2 years
measure: Change in Time to Complete a Twenty-meter Walk.
timeFrame: Baseline to 2 years
measure: Change in Time to Complete 5 Chair Stands.
timeFrame: Baseline to 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center / Division of Rheumatology
state: Massachusetts
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center / Division of Rheumatology
name: Timothy E. McAlindon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1967-1975. doi: 10.1001/jama.2017.5283.