Effect of Steroid Injections in a Knee With Osteoarthritis

NCT ID: NCT01230424

Last Updated: 2017-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2015-01-31

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.

Conditions

Osteoarthritis (OA) of the Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Triamcinolone Acetonide

40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Group Type: EXPERIMENTAL

Triamcinolone Acetonide

Intervention Type: DRUG

40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Sodium Chloride

0.9% Sodium chloride injection as Placebo will be given into the study knee once every 12 weeks for a total of 8 injections.

Group Type: PLACEBO_COMPARATOR

0.9% Sodium Chloride Injection as Placebo

Intervention Type: DRUG

Sodium chloride injection will be given into the study knee once every 12 weeks for a total of 8 injections.

Interventions

Triamcinolone Acetonide

40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Intervention Type: DRUG

0.9% Sodium Chloride Injection as Placebo

Sodium chloride injection will be given into the study knee once every 12 weeks for a total of 8 injections.

Intervention Type: DRUG

Other Intervention Names

Kenalog; Normal Saline for injection

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

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

Sponsors

Boston University

OTHER

Sponsor Role: collaborator

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy E. McAlindon, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center / Division of Rheumatology

Locations

Tufts Medical Center / Division of Rheumatology

Boston, Massachusetts, United States

Tufts Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28510679 (View on PubMed)

Other Identifiers

Tufts MC IRB Protocol # 9417

Identifier Type: OTHER

Identifier Source: secondary_id

NIH NIAMS R01-AR057802

Identifier Type: -

Identifier Source: org_study_id