PROPER Trial of Pain and Inflammation After Knee Arthroscopy (PROPER)

Early Reduction of Post-opeRative Pain and Inflammation to Expedite Return to Function After KNEE Arthroscopy

The purpose of this study is to determine if ceftriaxone administered postoperatively via intravenous injection reduces postoperative visual analog scale (VAS) pain scores and narcotic consumption in patients undergoing knee arthroscopy for a cartilage or meniscal injury.

Study Overview

• Status: Terminated
• Conditions: Cartilage Injury; Meniscus Lesion; Meniscus Tear
• Intervention / Treatment: Drug: Ceftriaxone; Other: Placebo

Detailed Description

Arthroscopic surgery for cartilage and meniscus injuries are some of the most common orthopaedic procedures currently performed. Post-surgical pain is initiated through an inflammatory response to surgery. The pain response leads to sleep disruption and a further increase in pain and additional sleep disruption. Opioid medications are often used after surgery to treat pain despite the side effect profile. These medications also contribute to poor sleep quality and duration. Early pain and narcotic use can be controlled by mitigating the effects of post-surgical inflammation. Ceftriaxone is a readily available antibiotic and may have the desirable anti-inflammatory and analgesic effects, but without the side effects caused by other medications. Since it is highly selective in its inhibition, ceftriaxone is an excellent candidate for reducing immediate post-operative pain and heightened inflammatory response.

By doing this study, the investigators hope to learn about the anti-inflammatory effectiveness of the antibiotic ceftriaxone. Ceftriaxone has been shown to inhibit a key enzyme in the post-operative inflammatory process and has been safely used for treatment of infections for years. The investigators would like to gather information about whether ceftriaxone helps reduce pain and inflammation after surgery. Participation in this research will last about 2 months.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Written consent to participate in the study
2. Male or female greater than or equal to 18 years of age and less than 55 years of age
3. Is indicated for knee arthroscopy for cartilage or meniscal procedure
4. Ambulatory and in good general health
5. Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions.
6. Willing to abstain from use of protocol-restricted medications during the study

Exclusion Criteria:

1. Known allergic reactions to cephalosporins
2. Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease
3. History of infection in either knee joint
4. Clinical signs and symptoms of active knee infection or crystal disease in either knee within 1 month of Screening
5. Other surgery or arthroscopy of either knee within 6 months of Screening
6. Intraarticular treatment of any joint with any of the following agents within six (6) months of Screening: any corticosteroid preparation or any biologic agent (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy, amniotic fluid injection; investigational or marketed).
7. Intraarticular treatment in either knee with hyaluronic acid (investigational or marketed) within 6 months of Screening
8. Parenteral or oral corticosteroids (investigational or marketed) within 3 months of Screening
9. Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening
10. Females who are pregnant or nursing or plan to become pregnant during the study; men whose female partner plans to conceive during the study
11. Radiographic osteoarthritic changes defined as Kellgren-Lawrence grade 2 or greater (as determined by PI from patient's preoperative X-rays)
12. Inability to read and understand English
13. Any prior diagnosis of antibiotic-resistant diarrhea

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; The experimental group will receive a single intravenous dose of 1 g of ceftriaxone immediately postoperative in the operating room.	Drug: Ceftriaxone; single intravenous dose of 1 g of ceftriaxone
Placebo Comparator: Placebo; The placebo group will receive a single intravenous dose of 1% lidocaine and saline immediately postoperative in the operating room.	Other: Placebo; 1% lidocaine and saline; Other Names: Lidocaine and Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analog Scale (VAS) Pain Score	The Visual analog scale scores range from 0 to 10 with greater scores indicative of greater pain.	Pre-operative, 2 months post-operative
Change in RU SATED Score	The Regularity, Sleep Quality, Alertness, Timing, Efficiency, Duration scale for sleep (RU SATED) ranges from 0 to 30, with higher scores indicating better sleep health.	Pre-operative, 2 months post-operative
Post-operative Narcotic Use	Post-operative narcotic use will be monitored with self-reported medication consumption at the first post-operative visit, which will take place 5-12 days post-operative. The milligrams of morphine equivalent (MME) will be calculated based on patient responses with greater MME indicative of increased postoperative use of narcotic pain medications.	5-12 days post-operative

Collaborators and Investigators

• Sponsor: Austin V Stone
• Investigators: Principal Investigator: Austin V Stone, MD, PhD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2021
• Primary Completion (Actual): April 29, 2022
• Study Completion (Actual): April 29, 2022

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Bacterial Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine; Ceftriaxone
• Other Study ID Numbers: 63476

Plan for Individual participant data (IPD)

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

IPD Plan Description

With the participant's approval and as approved by local Institutional Review Boards (IRBs), de-identified biological samples will be stored at the University of Kentucky Orthopedic Biomarker Repository. These samples could be used to research the causes of osteoarthritis after cartilage or meniscus injury, its complications and other conditions for which individuals with cartilage or meniscus injuries are at increased risk, and to improve treatment.

Before sharing biomarker samples, we will ensure that the participant has given previous consent to the sharing of the information or samples. When we confirm that the previously provided consent is still in effect we will remove identifiers such as (e.g., name, medical record number, or date of birth). We will use a secure electronic log to track information shared without releasing the individual participant's identity.

• IPD Sharing Time Frame: Access to individual participant data will be available 1 year after the final study follow-up has been completed, and will be available until 5 years after the final study follow-up has been completed.
• IPD Sharing Access Criteria: The researchers requesting access to participant information or samples must complete a questionnaire describing why they need information or samples for their research and how they will use the information or samples. The researchers who receive the information or samples will sign an agreement to use the data responsibly.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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.: Yes