Parabens Flocculation on the Anti Inflammatory Effects of Corticosteroid Injections for Total Knee Arthroplasty (5160373)

Clinical Significance of Parabens Flocculation on the Anti Inflrammmatory Effects of Corticosteroid Injection Osteoarthritic Knees

The purpose of this study is to identify whether corticosteroid use with anesthetics containing preservatives (parabens) reduces clinical effectiveness of the anti-inflammatory agent Up to 100 patients, both male and female, between the ages of 18-89 will be enrolled and randomized into either of the following groups; Group 1: These patients will receive a corticosteroid solution with lidocaine containing parabens.

Group 2: These patients will receive corticosteroid solution with paraben free lidocaine.

Study Overview

• Status: Withdrawn
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: corticosteroid solution with lidocaine containing parabens.; Drug: corticosteroid solution with lidocaine containing no paraben

Detailed Description

Corticosteroid injections have been used to treat inflammatory conditions for many decades (Storz 1973; Roszental, Zurakowski and Blazar 2008). In order to maximize the effectiveness on the synovial tissue, the concentrated form of corticosteroids is typically mixed with an anesthetic preparation. The corticosteroid suspension in a large volume of anesthetic can then disperse throughout the entire joint more effectively, especially in larger joints such as the knee (Centeno and Moore 1994). In addition, the anesthetic provides immediate relief to the area and can help verify that the injected site was the source of pain (Cole and Schumacher 2005). Typical preparations of anesthetic medications are sold in multi-use vials. The anesthetic solution usually contains a paraben preservative, except in the single vials used for spinal injections, because the use of paraben preservatives is contraindicated in spinal injections (Centeno and Moore 1994).

Celestone and Kenalog are two corticosteroid products that are commonly used for intra-articular injections. If co-administration of a local anesthetic is desired, the suspension of Celestone or Kenalog is commonly mixed with 1% or 2% Lidocaine hydrochloride from multi-use vials containing parabens in Orthopedic and Rheumatology clinics.

The orthopedic literature relating to injections rarely addresses the use of the anesthetic commonly used in injections. Flocculation occurs significantly when parabens are present, but the influence on the efficacy of the corticosteroid is unknown (Philipose et al. 2011; Hwang et al. 2016). There is abundant evidence that flocculation occurs when steroids are mixed with anesthetic solutions containing parabens however, the clinical significance of this phenomenon has not been reported. (Skedros and Pitts 2008b; Andreson, Deodhar and O'Rourke 2005; Skedros and Pitts 2008; Lutt, O'Rouke and Deodhar 2007; Cole and Schumacher 2005).

Cole and Schumacher (2005) suggest that flocculation can result from a chemical incompatibility between corticosteroid and other agents. Flocculation that occurs when corticosteroid is mixed with an anesthetic containing parabens may reduce the anti-inflammatory effect of the steroid. There are two possible mechanisms in which the corticosteroid preparation may be less effective. Flocculation may cause the corticosteroid to precipitate, thus reducing dispersal within the injected area (Centeno and Moore 1994). Additionally, flocculation may result from corticosteroid bonding with another molecule (such as methylparaben) within the anesthetic preparation, making it chemically less effective. The purpose of this study is to identify whether corticosteroid use with anesthetics containing parabens reduces clinical effectiveness relative to paraben-free preparations.

STUDY DESIGN:

OBJECTIVES:

The purpose of this study is to identify whether corticosteroid use with anesthetics containing parabens reduces clinical effectiveness relative to para-free preparations.

Hypothesis Alternate: Flocculation due to lidocaine containing parabens decreases the anti-inflammatory effects of corticosteroids when compared to paraben-free lidocaine.

Procedure:

The investigator will enroll up to 100 patients, both male and female, between the ages of 18-89. Once the patient has been consented, They will be randomized into group 1 or group 2. The randomization is a 1 to 1 ratio. Subsequent follow-up via phone call will take place on week 1, week 2, week 4, week 8, and week 16.

Group 1: These patients will receive a corticosteroid solution with lidocaine containing parabens.

Group 2: These patients will receive corticosteroid solution with paraben free lidocaine.

Corticosteroid injections will be given with or without ore-aspiration of synovial fluid. Patient will be in supine position with superior-lateral injection.

Material identification: Celestone soluspan or Kenalog 1% 50mL multiuse vials without epinephrine, 1% 5mL lidocaine vials, 10mL syringes with 21mm x 1 ¼ inch needles, alcohol swabs, exam gloves, betadine solution.

DATA COLLECTION:

The investigator will collect the patients age, sex, BMI, Medical history, along with the WOMAC survey, which asks about the patients knee and activity level and VAS, pain sale (0-10) 0 being the lease amount of pain and 10 being the worst.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health, Department of Orthopaedic Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 89 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of symptomatic primary knee osteoarthritis according to the American Rheumatism Association classification criteria for knee osteoarthritis, ability to understand study protocol and agreement to participate

Exclusion Criteria:

• History of any knee injection in the past 6 months, History of more than 2 injections in the knee under study, previous fracture or surgical procedure of knee under investigation, any benign or malignant tumor in knee, chemotherapy, hemearthosis, current infection in the affected limb.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; These patients will receive a corticosteroid solution with lidocaine containing parabens.	Drug: corticosteroid solution with lidocaine containing parabens.; To identify whether corticosteroid use with anesthetics containing parabens reduces clinical effectiveness relative to para-free preparations.
ACTIVE_COMPARATOR: Group 2; These patients will receive corticosteroid solution with paraben free lidocaine.	Drug: corticosteroid solution with lidocaine containing no paraben; To identify whether corticosteroid use with anesthetics containing parabens reduces clinical effectiveness relative to para-free preparations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC-Western Ontario and McMaster Universities Osteoarthritis Index	This is a survey that asks your view about your knee. This information will help track how you feel about your knee and how well you are able to do your usual activities	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS-Visual Analogue Scale	This is a Scale used to measure pain intensity. It is a continuous scale comprised of a horizontal line, usually 10cm or 100mm in length, the patient will mark a line between the two end-points, indicating there pain level.	6 months

Collaborators and Investigators

• Sponsor: Loma Linda University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 15, 2019
• Primary Completion (ANTICIPATED): October 15, 2019
• Study Completion (ANTICIPATED): October 30, 2019

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (ACTUAL): February 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 3, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: June 1, 2021

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; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine; Pharmaceutical Solutions
• Other Study ID Numbers: 5160373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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