N-Acetylcysteine Injection for Pilon Fracture
Trial Summary
What is the purpose of this trial?
High energy intra-articular fractures of the distal tibia, or Pilon fracture, is a devastating injury with multiple short and long term complications. The incidence of these injuries is increasing as survival rates after motor vehicle collisions increase. The current standard of care for high energy pilon fractures is to place an external fixator at the time of injury and then provide definitive internal fixation when the soft tissue envelope allows, which is usually around 10-14 days. Arguably, the most debilitating long term complication after a high energy pilon fracture is the development of post-traumatic osteoarthritis (PTOA), which occurs in 50% or more of pilon fractures within the first 2 years of surgery. The development of osteoarthritis occurs even in the presence of adequate restoration of the tibial plafond. Part of this issue lies in the fact that ankle joint cartilage is the thinnest of any major articular joint and sustains a great deal of damage at the time of injury. This impaction and injury initiates a cascade of events that ultimately result in cartilage cell death, or chondrolysis. Chondrolysis occurs via necrosis or apoptosis. Apoptosis occurs via a caspase pathway, while necrosis of chondrocytes likely occurs secondary to overproduction of reactive oxidant species (ROS). Recent animal models have demonstrated several things: chondrocyte death is highest along fracture lines, and likely undergo necrosis as opposed to apoptosis. The reason that PTOA likely occurs in such a high percentage of pilon fractures is because of this chondrolysis, and if a method can be developed to decrease the rate of chrondrocyte necrosis, then the rate of PTOA could potentially improve and improve patient outcomes overall. A recent bovine model examined the injection of N-acetylcysteine (NAC) after an intra-articular knee fracture and its effect on the cartilage cell viability. Their study demonstrated that chondrocyte cell viability after an injection of NAC within four hours of injury decreased chondrolysis from roughly 60% to about 30% at 48hrs. The effect was greater the closer to injury the injection occurred, and was statistically significant for 2 weeks. This indicates that free radical scavengers can potentially improve cartilage cell viability and help prevent the development of PTOA. No studies have been published on humans regarding injection of NAC after a fracture. However, a recent article examined the injection of NAC into osteoarthritic knees and found that it was effective in lowering certain cartilage degradation markers and was comparable to hyaluronic acid for both pain and function. NAC has been proven safe for both intra-articular injections and systemic injections in humans. Our study will focus on the improvement of cartilage cell viability with an injection of NAC. Our hypothesis is that the NAC intra-articular injection will increase the percentage of viable cartilage cell after sustaining a pilon fracture, when compared to a placebo injection of saline. The goal of this study is to examine the effects of an intra-articular injection of the amino acid NAC on cartilage cells after an intra-articular fracture of the ankle joint. The long-term clinical goal of this research is to reduce the incidence of post-traumatic osteoarthritis in the ankle joint after fracture.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.
What data supports the effectiveness of the drug N-acetylcysteine for pilon fracture?
N-acetylcysteine (NAC) has been shown to reduce the frequency of exacerbations in chronic obstructive pulmonary disease (COPD) and bronchiectasis, suggesting its potential as an effective treatment in conditions involving inflammation and oxidative stress, which may be relevant to pilon fractures.12345
Eligibility Criteria
This trial is for adults with a closed high-energy pilon fracture needing staged surgery. It's not for those under 18, with open fractures, NAC allergies, wounds that prevent safe injection, unwillingness to participate, pregnancy or if the injury doesn't require staged procedures.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Injection of N-acetylcysteine or saline at the time of external fixation
Definitive Surgery
Definitive internal fixation surgery and cartilage biopsy for cell viability analysis
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- N-acetylcysteine
- Saline
N-acetylcysteine is already approved in United States, European Union for the following indications:
- Acetaminophen overdose
- Chronic bronchitis
- Cystic fibrosis
- Mucolytic agent
- Paracetamol overdose
- Chronic bronchitis
- Cystic fibrosis
- Mucolytic agent
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Missouri-Columbia
Lead Sponsor