N-Acetylcysteine Injection for Pilon Fracture

Overseen By Vicki Jones, MEd, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Missouri-Columbia

Disqualifiers: Open fracture, Allergy to NAC, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of an injection of N-acetylcysteine (NAC) on cartilage cells in the ankle after a severe fracture. The goal is to determine if this treatment can reduce the risk of developing post-traumatic osteoarthritis, a painful joint condition common after such injuries. Participants will receive either the NAC injection or a saline (saltwater) injection when they first receive a stabilizing device for the fracture. This study may suit individuals with a closed, high-energy pilon fracture requiring a staged procedure. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for N-acetylcysteine and saline treatments?

Research has shown that N-acetylcysteine (NAC) is safe for humans. Studies have found that NAC is well tolerated when injected into joints or taken in other forms. In animal studies, NAC improved the health of cartilage cells after an injury. In humans, NAC injections have been compared to treatments like hyaluronic acid for joint issues, and both helped with pain and movement. These findings suggest that NAC is generally safe and could be a promising option for improving joint health after an injury. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard care for pilon fractures, which typically involves surgical fixation and lengthy rehabilitation, N-acetylcysteine (NAC) offers a novel approach by being administered as an injection at the time of external fixation. Researchers are excited because NAC acts as an antioxidant, potentially reducing inflammation and accelerating healing. This could lead to quicker recovery times and improved outcomes for patients, setting it apart from traditional methods that don't directly target oxidative stress.

What evidence suggests that N-acetylcysteine might be an effective treatment for pilon fractures?

Research has shown that injecting N-acetylcysteine (NAC) into a joint after a fracture might protect the cartilage. In animal studies, NAC reduced cartilage cell death from about 60% to 30% when administered soon after the injury. This trial will test NAC in one of its treatment arms, where participants will receive an injection of NAC during external fixation. NAC could limit damage and possibly reduce the risk of developing post-traumatic osteoarthritis, a common issue after serious fractures. Although NAC hasn't been tested on human fractures yet, it has shown promise in treating osteoarthritic knees by reducing signs of cartilage breakdown. NAC is considered safe for joint injections and might help maintain joint health after an injury. Another arm of this trial will use a saline injection as a placebo comparator. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

You have a severe fracture in your leg that needs to be treated with multiple surgeries.

Exclusion Criteria

Younger than 18

Open fracture

Wounds preventing safe intra-articular injection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Injection of N-acetylcysteine or saline at the time of external fixation

2 weeks

1 visit (in-person)

Definitive Surgery

Definitive internal fixation surgery and cartilage biopsy for cell viability analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine
• Saline

Trial Overview The study tests whether injecting N-acetylcysteine (NAC) into the ankle joint after a pilon fracture can keep more cartilage cells alive compared to a placebo saline injection. The aim is to see if this can reduce post-traumatic osteoarthritis.

How Is the Trial Designed?

Group I: N-acetylcysteine (NAC) Experimental Treatment 1 Intervention

Injection of N-acetylcysteine at the time of external fixation

Group II: Saline Placebo Group 1 Intervention

Injection of saline at the time of external fixation

N-acetylcysteine is already approved in United States, European Union for the following indications:

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

In a 12-month study involving 161 bronchiectasis patients, those treated with N-acetylcysteine experienced significantly fewer exacerbations (1.31 vs. 1.98 per patient-year) compared to the control group, indicating its efficacy in reducing flare-ups.

The N-acetylcysteine group also showed a notable improvement in quality of life and a significant reduction in sputum volume, with no severe adverse events reported, suggesting it is a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Qi, Q., Ailiyaer, Y., Liu, R., et al.[2020]

N-acetylcysteine (NAC) significantly reduced the rate of healthcare resource utilization (HCU) events related to COPD exacerbations by 20% compared to placebo, with an even greater reduction of 23% in current and ex-smokers.

In patients using long-acting bronchodilators without inhaled corticosteroids (ICS), NAC led to a remarkable 60% reduction in exacerbation rates compared to those receiving placebo, suggesting NAC could be a beneficial alternative to ICS in certain COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. Papi, A., Zheng, J., Criner, GJ., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-4-fractures-bone-2019-c69c7

N-Acetylcysteine Injection for Pilon Fracture Trial Overview The study tests whether injecting N-acetylcysteine (NAC) into the ankle joint after a pilon fracture can keep more cartilage cells alive compared ...

2. clinicaltrial.be clinicaltrial.be/en/details/67400?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Pilon Fracture With Intra-articular Injection of N-Acetyl... Their study demonstrated that chondrocyte cell viability after an injection of NAC within four hours of injury decreased chondrolysis from ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7104386/

N-Acetyl Cysteine Treatment Restores Early Phase ... We hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5987523/

Targeting mitochondrial responses to intra-articular fracture to ... The efficacy of NAC, a compound that supports thiol redox metabolism ... sustaining high energy pilon fractures (7, 8). The high progression rate for ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772964823000102

Retrograde reduction for a depressed talus fracture ... The postoperative outcome was satisfactory, and no signs of osteoarthritis or osteonecrosis of the talus were identified 1 year after the injury. Retrograde ...

6. clinicaltrialsgps.com clinicaltrialsgps.com/search-clinical-trials/trial-90597/?Location=112966

Pilon Fracture With Intra-articular Injection of N ... NAC has been proven safe for both intra ... will increase the percentage of viable cartilage cell after sustaining a pilon fracture, when

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC Studies with a dosage up to 3000 mg/day in respiratory diseases have shown that NAC is safe and well tolerated [27] (Table 2). The clinical efficacy of NAC for ...