Intra-articular Injections for Knee Osteoarthritis: A Single Blinded Prospective Randomized Trial

Early Phase 1

Withdrawn

• Conditions: Symptomatic Osteoarthritis of the Knee
• Interventions: Drug: Air 10 ml; Drug: Normal Saline 10 ml; Drug: 40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine

• Registration Number: NCT02995083
• Lead Sponsor: Rush University Medical Center

Brief Summary

To investigate the clinical benefit of intra-articular injections of saline in patients with symptomatic osteoarthritis of the knee and compare the clinical response of saline to the current standard treatment with corticosteroids and an air injection placebo.

Detailed Description

As non-surgical treatments of OA are essential, multiple trials have been done to compare standard of care IA injection therapies to more novel injection treatments, with many of these trials using saline as the control arm. The purpose of using a control arm is to attempt to eliminate placebo effect and help distinguish the true effectiveness of a therapy. There has been controversy over the clinical effect of saline in treating OA with some arguing that saline may have some clinical benefit. If this is true, it could allow for the true effect of standard of care therapies to appear diminished when compared to saline as a placebo. A recent meta analysis looked at the use of saline as a placebo in 38 randomized control trials to determine if intra-articular saline injections for knee OA had a clinical effect. The study found that IA injections of saline significantly improved short-term knee pain in 32 of the studies which involved 1705 patients, p \<0.001, and long-term pain was significantly decreased in 19 of the studies involving 1445 patients, p \<0.001. It is essential to empirically determine if saline has a clinical effect due to the role it plays as a placebo in many clinical studies of the management of OA with intra-articular injections.

Objective: To investigate the clinical benefit of intra-articular injections of saline in patients with symptomatic osteoarthritis of the knee and compare the clinical response of saline to the current standard treatment with corticosteroids and an air injection placebo.

Study Design: Prospective, single-blinded, randomized, clinical study. Patients will be randomized into three treatment arms in a 1:1:1 fashion with approximately 50 patients in the saline arm, 50 patients in the corticosteroid arm, and 50 patients in the placebo arm.

Null Hypothesis: Clinical knee outcomes of subjects following one intra-articular knee injection of air will be similar to one intra-articular knee injection of saline or corticosteroid for symptomatic patients diagnosed with knee OA.

Statistical Assumptions: Power Analysis

Investigational Arm: 10 ml Saline (Normal Saline)

Control Arm: 1 ml of 40 mg corticosteroid in 9 ml 1% lidocaine (Depo-medrol, Pfizer, New York, New York), 10 ml air (placebo)

Primary Efficacy Endpoint: The primary efficacy endpoint is the mean change in the WOMAC Index score 12 weeks after first injection with regards to baseline score.

Secondary Efficacy Secondary efficacy endpoints include the change in the full Endpoints: WOMAC Index, KOOS, Lysholm, IKDC, VAS, SF-12 and use of rescue medication (steroid at 12 weeks).

Enrollment: Prospective, randomized, clinical study designed to evaluate 150 subjects. All enrolled subjects will have a pre-procedure visit, one treatment visit, and follow-up visits at week 6 and week 12 if they require a rescue injection and will fill out patient reported outcome measures at 1, 6, 12, and 24 weeks.

Study Timeline

• Study First Submitted: 2016-12-14
• Study First Submitted QC: 2016-12-14
• Study First Posted: 2016-12-16
• Study Start: 2017-06
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-14
• Last Update Posted: 2017-12-18
• Primary Completion: 2018-01
• Study Completion: 2018-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. The patient must be between the ages of 18 and 80
2. Informed consent has been obtained from the patient
3. The patient must have diagnosed symptomatic osteoarthritis of the tibio-femoral or patello-femoral compartment of the target knee for at least 1 month
4. The patient has moderate-to-severe knee pain reflected by an average visual analogue scale (VAS) score of 4 or greater (out of a possible 10) over the previous 7 days.
5. Radiographic imaging must show grade II-III osteoarthritis on the Kellgren & Lawrence Scale.
6. Patients may have bilateral osteoarthritis but only patients with unilateral symptoms may be included.

Exclusion Criteria

1. Knee instability
2. A score less than 4 (out of a possible 10) on their intake VAS
3. Major axial deviation (>5º valgus or varus deviation as evidenced on a standard of care x-ray.
4. Previous surgery at the target knee < 6 months.
5. Symptomatic osteoarthritis of the contralateral knee or any other joint.
6. Systemic or intra articular injection to any joint with corticosteroids within 6 months prior to screening
7. Previous joint injection of any type in the past 6 months
8. Systemic conditions that could interfere with outcome such as Rheumatoid arthritis, coagulopathy, and anemia.
9. Allergy to any of the injected substances.
10. Any patient unable to cease NSAID usage (other than low dose aspirin) due to unrelated condition.
11. Cognitive impairment or unable to provide informed consent
12. Recent knee trauma with violation of the intra-articular bone.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Knee injection with air	Air 10 ml	Using clinically accepted methods, subjects will undergo a palpation guided injection of air into the knee joint. Subjects will then return for follow-up visit at 12 weeks for a physical exam of the knee. Patients will fill out questionnaires online at 1, 6, 12 and 24 weeks.
Knee injection with saline	Normal Saline 10 ml	Using clinically accepted methods, subjects will undergo a palpation guided injection of saline into the knee joint. Subjects will then return for follow-up visit at 12 weeks for a physical exam of the knee. Patients will fill out questionnaires online at 1, 6, 12 and 24 weeks.
Knee injection with corticosteroids	40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine	Using clinically accepted methods, subjects will undergo a palpation guided injection of corticosteroids into the knee joint. Subjects will then return for follow-up visit at 12 weeks for a physical exam of the knee. Patients will fill out questionnaires online at 1, 6, 12 and 24 weeks.

Primary Outcome Measures

Name	Time	Method
Mean change in Western Ontario and McMaster Universities Arthritis Index score (WOMAC)	12 weeks after injection	Mean change in the WOMAC Index score from baseline score

Secondary Outcome Measures

Name	Time	Method
Mean change in Short Form 12 (SF-12) score	12 weeks after injection	Mean change in SF-12 from baseline score
Mean change in International Knee Documentation Committee (IKDC) score	12 weeks after injection	Mean change in IKDC from baseline score
Mean change in Knee injury and Osteoarthritis Outcome Score (KOOS)	12 weeks after injection	Mean change in the KOOS from baseline score
Mean change in Visual Analogue Scale (VAS)	12 weeks after injection	Mean change in VAS from baseline score
Mean change in The Lysholm Knee score	12 weeks after injection	Mean change in The Lysholm Knee score from baseline score
Mean change in use of rescue medication	12 weeks after injection	Use of anti-inflammatory, analgesics, and rescue corticosteroid injection. Number of pills taken each day. This will be collected via survey. If the medical examiner feels that the patient is continuing to do poorly and they did not receive the steroid injection intervention, then they will be offered a rescue corticosteroid injection at 12 weeks. The number of patients who do not initially receive a corticosteroid injection and require a rescue corticosteroid injection at 12 weeks will be recorded.