Success of Long-acting Anti-inflammatories After Anterior Cruciate Ligament and Meniscal Injury

NCT04331002 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 53136
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if extended-release triamcinolone acetonide treatment alters the progressive changes in bone shape previously demonstrated after anterior cruciate ligament (ACL) reconstruction with partial meniscectomy or meniscal repair.

Conditions

Tibial Meniscus Injuries; Tibial Meniscus Tears; Tibial Meniscus, Torn; Anterior Cruciate Ligament Tear

Keywords

Knee; Meniscectomy; Meniscus Repair; Anti-inflammatory; Anterior cruciate ligament

Outcome Measures

Primary Outcomes (1)

• Change in Bone Shape (Baseline to 4 Months)

  Using manual segmentation, the volume of the medial femoral condyle will be quantified from 3-Tesla magnetic resonance imaging (MRI) scans performed before and 4 months after the study injection. Medial condyle volume will be expressed as cm3.

  Baseline, 4 months

Secondary Outcomes (10)

• Change in IKDC (Baseline to 4 Months)

  Baseline, 4 months, 1 year, 2 years

• Change in IKDC (Baseline to 1 Year)

  Baseline, 4 months, 1 year, 2 years

• Change in IKDC (Baseline to 2 Years)

  Baseline, 4 months, 1 year, 2 years

• Change in KOOS Global (Baseline to 4 Months)

  Baseline, 4 months, 1 year, 2 years

• Change in KOOSglobal (Baseline to 1 Year)

  Baseline, 4 months, 1 year, 2 years

Study Arms (2)

Experimental

EXPERIMENTAL

The experimental group will receive a single 32 mg Zilretta injection approximately 8 weeks after meniscus surgery.

Drug: Zilretta

Placebo

PLACEBO COMPARATOR

The placebo group will receive a single 5 mL injection of normal saline approximately 8 weeks after meniscus surgery.

Other: Placebo

Interventions

Zilretta DRUG

ZILRETTA is an injectable suspension that delivers 32 mg of triamcinolone acetonide. It is supplied as a single-dose kit containing one vial of ZILRETTA microsphere powder, one vial of 5 mL diluent, and one sterile vial adapter.

Also known as: Extended release triamcinolone acetonide

Experimental

Placebo OTHER

5 mL normal saline

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written consent to participate in the study
• Male or female greater than or equal to 18 years of age and less than 40 years of age
• Has been consented to undergo arthroscopic ACL reconstruction with partial meniscectomy or meniscal repair
• Ambulatory and in good general health
• Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions.
• Willing to abstain from use of protocol-restricted medications during the study
• Females and males who have reproductive potential: Must use highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation (10 weeks; 4 to 14 weeks after surgery)
• Demonstrate persistent inflammation defined as synovial fluid IL-1a concentration greater than or equal to 5 pg/mL at the time of surgery

You may not qualify if:

• Known allergic reactions to components of the extended-release triamcinolone acetonide (Zilretta®)
• Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease
• History of infection in either knee joint
• Clinical signs and symptoms of active knee infection or crystal disease in either knee within 1 month of Screening
• Other surgery or arthroscopy of either knee within 6 months of Screening
• 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).
• Intraarticular treatment in either knee with hyaluronic acid (investigational or marketed) within 6 months of Screening
• Parenteral or oral corticosteroids (investigational or marketed) within 3 months of Screening
• Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening
• Females who are pregnant or nursing or plan to become pregnant during the study; men whose female partner plans to conceive during the study
• Radiographic osteoarthritic changes defined as Kellgren-Lawrence grade 2 or greater (as determined by PI from patient's preoperative X-rays)
• Inability to read and understand English

Sponsors & Collaborators

• Austin V Stone: lead

Study Sites (1)

UK Healthcare at Turfland

Lexington, Kentucky, 40504, United States

Location

MeSH Terms

Conditions

Tibial Meniscus Injuries; Anterior Cruciate Ligament Injuries

Interventions

Triamcinolone; Sodium Chloride

Condition Hierarchy (Ancestors)

Leg Injuries; Wounds and Injuries; Knee Injuries

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Austin Stone
• Organization: University of Kentucky

austin.stone@uky.edu

859-218-3131

Study Officials

• Austin Stone, MD, PhD

  University of Kentucky

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The knee will be aspirated and one group will receive a single 32 mg Zilretta injection and the other group will receive a 5 mL saline injection. The syringes will be blinded to ensure that both the investigator administering the injection and the patient will be blinded to the group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: After providing informed consent prior to ACL reconstruction with meniscal involvement, synovial fluid will be collected and assessed for the concentration of pro-inflammatory cytokine interleukin-1alpha (IL-1a). This will be done to identify patients that present with persistent inflammation after surgery that may be at increased risk of cartilage degradation. Patients with elevated IL-1a, defined as concentrations \> 5 pg/mL, will then be randomized to one of two groups. The threshold of 5 pg/mL was based on our pilot study of 19 patients. For those with elevated IL-1a, eight weeks after surgery the knee will be aspirated and one group will receive a single 32 mg Zilretta injection and the other group will receive a 5 mL saline injection.

Study Record Dates

• First Submitted: July 27, 2019
• First Posted: April 2, 2020
• Study Start: August 21, 2020
• Primary Completion: July 11, 2022
• Study Completion: July 11, 2022
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• 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.
• 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.

Locations

US (1)