Trial Comparing Three Single Dose Injections for Knee Osteoarthritis

A Double-blind, Randomized Trial Comparing Three Single Dose Injections for Knee Osteoarthritis

This study is a 3-arm, double-blind, randomized trial comparing the clinical outcomes of Zilretta, Synvisc One, and Monovisc for knee OA.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Zilretta; Drug: Synvisc-One 48 MG in 6 ML Prefilled Syringe; Drug: Monovisc 88 MG Per 4 ML Prefilled Syringe

Detailed Description

Knee osteoarthritis (OA) is a leading cause of disability worldwide.1,2 Standard of care treatments for knee OA include activity modification, weight loss, therapeutic exercise and medications like non-steroidal anti-inflammatory drugs (NSAIDs). If these measures fail, injections like corticosteroids and hyaluronate (HA) can be helpful for pain control.3

The aforementioned injections have unique mechanisms of action. Steroid injections work through reducing joint inflammation, while HA works by lubricating and cushioning the joint. There are several varieties of steroids and HA injections that have been approved by the Food and Drug Administration for use in knee OA.

Among these variations are extended-release triamcinolone (Zilretta), hylan GF-20 (synvisc one), and hyaluronan (monovisc). While each are FDA approved and commonly used in orthopedic and sports medicine clinics, they have never been directly compared in any study. Therefore, when selecting a treatment for a patient, it is largely based on provider preference, not clinical data.

This study is a 3-arm, double-blind, randomized trial comparing the clinical outcomes of Zilretta, Synvisc One, and Monovisc for knee OA.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michael Keller; Phone Number: (614) 293-2410; Email: michael.keller@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43202
      • Jameson Crane Sports Medicine Institute
    • Lewis Center, Ohio, United States, 43035
      • Ohio State Outpatient Lewis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 25-85 years
• BMI < 40
• Diagnosis of unilateral knee OA
• Radiographic evidence of OA of the target knee (Kellgren-Lawrence grades 2-4)
• Continued OA pain in the target knee despite at least 6 weeks of: physical therapy and at least one of the following: activity modification (such as reducing impact on the knee), weight loss, and a 2 week trial of NSAID / acetaminophen.
• Knee Osteoarthritis Outcomes Score (KOOS)-Pain subscale 20-65
• Working knowledge of English language (to be able to complete all outcome scores)
• Ability to attend all follow-up appointments

Exclusion Criteria:

• 3+ effusion of the target knee (stroke test grading system)

• Prior injection therapy:

  • Steroid injection in target knee in the last 3 months
  • Viscosupplementation in target knee in the last 6 months
  • PRP in the target knee in the last 6 months
  • Cellular treatments in index knee (bone marrow, amniotic suspensions etc) 1 year
  • Participation in any experimental device or drug study within 1 year before screening visit
• Oral or IM steroids in the last 3 months (Inhaled steroids used in the treatment of asthma/allergies are permitted)

• Medical condition that may impact outcomes of procedure including:

  • Systemic inflammatory disorders that impact the joints like rheumatoid arthritis, lupus, etc
  • Undergoing current cancer treatment (other than non-melanoma skin malignancies)
• Taking immunosuppressants
• Previous cartilage repair procedure on the injured cartilage surface (ie, OATS, ACI, MFX) in the last 5 years
• Previous surgery at the target knee within the past 1 year
• Any degree of cognitive impairment
• Symptomatic OA of any other joint in the lower limbs
• Pregnancy, lactating, or intent to become pregnant during treatment period (Female participants will be asked if they are pregnant, lactating, or intend to become pregnant during treatment)
• Gout, Pseudogout (including radiographic evidence of chondrocalcinosis)
• History of infection or current infection at the affected joint
• Smoking (Former smokers< 1 year from quit date)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zilretta; Generic Name: Triamcinolone acetonide Zilretta is an extended-release synthetic corticosteroid indicated as an intra-articular injection for the management ofosteoarthritis pain of the knee. 5mL suspension of 32 mg of triamsinolone administered as a 1 dose parapatellar intra-articular injection.	Drug: Zilretta; Intra-articular injection to treat knee osteoarthritis
Active Comparator: Synvisc One; Generic Name: Hylan G-F 20 Synvisc-One combines the three doses of SYNVISC (hylan G-F 20) which consists of hylan A (average molecular weight6,000,000 daltons) and hylan B hydrated gel in a buffered physiological sodium chloride solution, pH 7.2. Each 10 mL syringe of Synvisc-One combines the three 2-mL doses (16 mg each) of a complete SYNVISC treatment regimen (48 mg). Synvisc-One belongs to a class of drugs called Intra-Articular Agents; Rheumatologics, Other. 10mL of Hylan G-F 20 administered as a 1 dose parapatellar intra-articular injection.	Drug: Synvisc-One 48 MG in 6 ML Prefilled Syringe; Intra-articular injection to treat knee osteoarthritis
Active Comparator: Monovisc; Generic Name: Hyaluronan The Monovisc™ device is a proprietary high molecular weight hyaluronic acid (HA) viscosupplementation intended for the treatment of pain in patients with moderate osteoarthritis (OA) of the knee who have failed conservative non-pharmacological therapy and simple analgesics. The device is administered by a single injection via the para-patellar approach under sterile conditions. 4mL injection of Hyaluronan administered as a 1 dose parapatellar intra-articular injection.	Drug: Monovisc 88 MG Per 4 ML Prefilled Syringe; Intra-articular injection to treat knee osteoarthritis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee injury and Osteoarthritis Outcome Score (KOOS) Pain patient reported outcome questionnaire	KOOS Pain evaluates short-term and long-term pain in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee pain.	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms patient reported outcome	KOOS symptoms evaluates short-term and long-term symptoms in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee symptoms.	Baseline, 3 month, 6 month
Knee injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) patient reported outcome	KOOS ADL evaluates short-term and long-term function in daily living in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to daily living activity.	Baseline, 3 month, 6 month
Knee injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation (Sport/Rec) patient reported outcome	KOOS Sport/Rec evaluates short-term and long-term function in sports and recreation in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to sports or recreation activity.	Baseline, 3 month, 6 month
Knee injury and Osteoarthritis Outcome Score (KOOS) knee related quality of life (QOL) patient reported outcome	KOOS QOL evaluates short-term and long-term knee quality of life in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to quality of life.	Baseline, 3 month, 6 month
Knee injury and Osteoarthritis Outcome Score (KOOS) Pain patient reported outcome	KOOS Pain evaluates short-term and long-term pain in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee pain.	Baseline, 3 month

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Michael Baria, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Actual): January 11, 2023
• Study Completion (Actual): January 11, 2023

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Protective Agents; Viscosupplements; Hylan
• Other Study ID Numbers: 2022H0168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IDP will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No