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

NCT ID: NCT02995083

Last Updated: 2017-12-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-30
• Study Completion Date: 2018-01-31

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.

Conditions

Symptomatic Osteoarthritis of the Knee

Keywords

osteoarthritis

Study Design

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

Study Groups

Knee injection with corticosteroids

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.

Group Type: ACTIVE_COMPARATOR

40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine

Intervention Type: DRUG

Patients will receive an ultrasound guided intra-articular injection of 40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine

Knee injection with saline

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.

Group Type: PLACEBO_COMPARATOR

Normal Saline 10 ml

Intervention Type: DRUG

Patients will receive an ultrasound guided intra-articular injection of Normal Saline 10 ml

Knee injection with air

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.

Group Type: SHAM_COMPARATOR

Air 10 ml

Intervention Type: DRUG

Patients will receive an ultrasound guided intra-articular injection of Air 10 ml

Interventions

40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine

Patients will receive an ultrasound guided intra-articular injection of 40 mg Depo-Medrol in 1 ml, 9 ml of 1% lidocaine

Intervention Type: DRUG

Normal Saline 10 ml

Patients will receive an ultrasound guided intra-articular injection of Normal Saline 10 ml

Intervention Type: DRUG

Air 10 ml

Patients will receive an ultrasound guided intra-articular injection of Air 10 ml

Intervention Type: DRUG

Other Intervention Names

Corticosteroid; Saline; Air

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rush University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Mukesh Ahuja

Certified Principal Investigator, Research Administrator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nikhil N Verma, MD

Role: PRINCIPAL_INVESTIGATOR

Midwest Orthopaedics at Rush University

References

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Reference Type: BACKGROUND

PMID: 18759314 (View on PubMed)

Altman RD, Devji T, Bhandari M, Fierlinger A, Niazi F, Christensen R. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum. 2016 Oct;46(2):151-159. doi: 10.1016/j.semarthrit.2016.04.003. Epub 2016 Apr 27.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 24009911 (View on PubMed)

Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008 Dec;67(12):1716-23. doi: 10.1136/ard.2008.092015. Epub 2008 Jun 9.

Reference Type: BACKGROUND

PMID: 18541604 (View on PubMed)

Eker HE, Cok OY, Aribogan A, Arslan G. The efficacy of intra-articular lidocaine administration in chronic knee pain due to osteoarthritis: A randomized, double-blind, controlled study. Anaesth Crit Care Pain Med. 2017 Apr;36(2):109-114. doi: 10.1016/j.accpm.2016.05.003. Epub 2016 Jul 30.

Reference Type: BACKGROUND

PMID: 27485803 (View on PubMed)

Other Identifiers

16090902

Identifier Type: -

Identifier Source: org_study_id