Effect of Steroid Injections in a Knee With Osteoarthritis

Phase 4

Completed

Conditions: Osteoarthritis (OA) of the Knee

Interventions: Drug: 0.9% Sodium Chloride Injection as Placebo
Drug: Triamcinolone Acetonide

Registration Number: NCT01230424

Lead Sponsor: Tufts Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium Chloride	0.9% Sodium Chloride Injection as Placebo	0.9% Sodium chloride injection as Placebo will be given into the study knee once every 12 weeks for a total of 8 injections.
Triamcinolone Acetonide	Triamcinolone Acetonide	40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Primary Outcome Measures

Name	Time	Method
Change in Mean Cartilage Thickness in the Index Compartment (Compartment With the Most Damage)	Baseline to 2 years	Mean cartilage thickness was measured on knee MRI (Philips Achieva X-Series 3.0 Tesla scanner). Missing data were imputed.
Change in Knee Pain Severity During the Past 48 Hours From the WOMAC LK3.1 Pain Score Questionnaire.	Baseline to 2 years	Pain subscale score was calculated from patient's responses on the Western Ontario and McMaster Universities Osteoarthritis Index Likert-type 3.1 Questionnaire. The questionnaire includes 24 items divided into 3 subscales, Pain, Stiffness, Physical Function. Only the Pain subscale score was used for this outcome measure. The Pain subscale consists of five items, each ranging from 0 to 4, making the total Pain subscore 0 to 20. Higher scores represent higher levels of pain, whereas lower scores represent lower levels of pain. Missing data were imputed.

Secondary Outcome Measures

Name	Time	Method
Change in Volume of Peri-articular Bone Marrow Lesions Measured on Knee MRI.	Baseline to 2 years.	Change in volume of peri-articular bone marrow lesions measured on knee MRI on the log scale. Missing data were imputed.
Change in Effusion Volume Measured on Knee MRI.	Baseline to 2 years	Change in effusion volume measured on knee MRI on the log scale. Missing data were imputed.
Change in Area of Denudation Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).	Baseline to 2 years	Change in area of denudation measured on knee MRI in the index compartment (compartment with the most damage). Missing data were imputed.
Change in Volumetric Cartilage Damage Index (CDI) Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).	Baseline to 2 years	Change in volumetric cartilage damage index (CDI) measured on knee MRI in the index compartment (compartment with the most damage). Missing data were imputed.
Change in Function Severity During the Past 48 Hours From the WOMAC LK3.1 Function Score Questionnaire.	Baseline to 2 years	Physical Function subscale score was calculated from patient's responses on the Western Ontario and McMaster Universities Osteoarthritis Index Likert-type 3.1 Questionnaire. The questionnaire includes 24 items divided into 3 subscales, Pain, Stiffness, Physical Function. Only the Physical Function subscale score was used for this outcome measure. The Physical Function subscale consists of 17 items, each ranging from 0 to 4, making the total Function subscore 0 to 68. Higher scores represent higher levels of difficulty performing daily activities, whereas lower scores represent lower levels of difficulty performing daily activities. Missing data were imputed.
Change in Knee Stiffness During the Past 48 Hours From the WOMAC LK3.1 Stiffness Score Questionnaire.	Baseline to 2 years	Stiffness subscale score was calculated from patient's responses on the Western Ontario and McMaster Universities Osteoarthritis Index Likert-type 3.1 Questionnaire. The questionnaire includes 24 items divided into 3 subscales, Pain, Stiffness, Physical Function. Only the Stiffness subscale score was used for this outcome measure. The Stiffness subscale consists of two items, each ranging from 0 to 4, making the total Stiffness subscore 0 to 8. Higher scores represent higher levels of stiffness, whereas lower scores represent lower levels of stiffness. Missing data were imputed.
Change in Patient's Global Assessment (Visual Analogue Scale).	Baseline to 2 years	The response to the question, "Considering all the ways your knee affects you, how much pain are you having today?", was measured and the change in the scoring was evaluated. The Patient's Global Assessment (PGA) is measured on a scale of 0 to 100 millimeters. Higher scores represent a higher level of disease activity or a worse global health. Missing data were imputed.
Change in Time to Complete a Twenty-meter Walk.	Baseline to 2 years	Change in time (seconds) to complete a twenty-meter walk. Missing data were imputed.
Change in Time to Complete 5 Chair Stands.	Baseline to 2 years	Change in time (seconds) to complete 5 chair stands. Missing data were imputed.

Trial Locations

Locations (2): Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Tufts Medical Center / Division of Rheumatology
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Boston, Massachusetts, United States