Ibuprofen for Pain in Tibial Fractures

(NSAID Trial)

Recruiting at 13 trial locations

Overseen By Thomas Higgins, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Major Extremity Trauma Research Consortium

Must not be taking: NSAIDs, Aspirin, Glucocorticoids

Disqualifiers: Drug use, Allergy, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding ibuprofen, a common pain reliever, to standard pain management is as effective as standard pain management alone for individuals with certain types of shinbone fractures (tibial shaft fractures). The goal is to determine if ibuprofen can aid recovery without causing additional issues. Participants will be divided into two groups: one will receive standard care without ibuprofen, while the other will include ibuprofen in their treatment. This trial may suit individuals who have had a shinbone fracture treated with a nail and can attend follow-ups at a participating facility for a year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you require a regular aspirin or NSAID regimen, except for low-dose aspirin (81mg).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ibuprofen is generally safe for pain relief. However, safety concerns arise when used after a bone fracture. Some studies suggest that NSAIDs like ibuprofen might slow or hinder proper bone healing. Specifically, one study found that the risk of improper bone healing was about three times higher in individuals who took NSAIDs after a fracture.

When considering participation in this trial, weighing these risks against the benefits of pain relief is crucial. While ibuprofen can alleviate pain, its effect on bone healing requires careful consideration, particularly after a recent fracture. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for tibial fractures?

Unlike the standard of care for tibial fracture pain, which often involves opioids and other pain relievers without NSAIDs, ibuprofen offers a non-opioid alternative with anti-inflammatory properties. Researchers are excited about ibuprofen because it targets inflammation directly, which is a significant component of pain in fractures, potentially reducing the need for stronger painkillers that can have more severe side effects. Additionally, ibuprofen is widely available and generally well-tolerated, making it a cost-effective and accessible option for patients.

What evidence suggests that this trial's treatments could be effective for pain in tibial fractures?

Research has shown that ibuprofen, a common pain reliever, effectively reduces pain in the first week after a fracture. One study found that people taking ibuprofen experienced significantly less pain during this period compared to those who did not. In this trial, one group of participants will receive standard care pain management with NSAIDs, including ibuprofen, while another group will receive standard care without NSAIDs. Concerns exist that ibuprofen might slow bone healing, with some studies suggesting it could delay healing in certain cases. However, other research indicates that short-term use of ibuprofen does not significantly increase the risk of improper bone healing. Overall, ibuprofen can effectively manage pain without major risks if used carefully for a short period. ^{2 3 4 6 7}

Who Is on the Research Team?

Thomas Higgins, MD

Principal Investigator

University of Utah

Renan Castillo, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals with tibial shaft fractures. Participants should be experiencing pain and may have conditions like anosognosia or chronic persistent surgical pain. The study excludes those who cannot take NSAIDs due to medical reasons, but specific exclusion criteria are not listed.

Inclusion Criteria

I have a tibia fracture treated with a nail.

I am between 18 and 80 years old.

Patients able to be followed at a METRC facility for at least 12 months following injury

Exclusion Criteria

My consciousness level was below normal when I left the hospital.

I am scheduled for a bone graft during my initial surgery.

I need to take aspirin or NSAIDs, but only take low dose aspirin (81mg).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard pain management with or without NSAIDs for up to 6 weeks

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and union of tibia fractures

12 months

3 visits (in-person) at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibuprofen

Trial Overview The trial compares standard pain management alone (Group 1) versus standard pain management plus up to six weeks of Ibuprofen, an NSAID (Group 2), in treating tibial fractures. It's a Phase III noninferiority trial conducted across multiple centers.

How Is the Trial Designed?

Group I: Standard of Care Pain Management without NSAIDs Active Control 1 Intervention

Control patients will receive standard of care pain medication regimen and may not use NSAIDs. Clinicians in this group may use whatever further analgesia they desire, excluding NSAIDs.

Group II: Standard of Care Pain Management with NSAIDs Active Control 1 Intervention

Treatment patients will receive oral ibuprofen 600 mg three times a day (tid) for up to six weeks. Clinicians in this group may use whatever further analgesia they desire, excluding NSAIDs. For patients who have a clinical concern regarding NSAID and prophylactic anticoagulation, the treating physician may consider prescribing misoprostol.

Who Is Running the Clinical Trial?

Major Extremity Trauma Research Consortium

Lead Sponsor

Trials

32

Recruited

27,400+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30270011/

Tibia fractures and NSAIDs. Does it make a difference? ... Our study suggests that NSAIDs may be used safely and effectively in the acute phase of fracture healing without significantly increasing the risk of delayed ...

2. tsaco.bmj.com tsaco.bmj.com/content/8/1/e001056

Efficacy and safety of non-steroidal anti-inflammatory drugs ... The ibuprofen groups had significantly less pain in the first 7 days after fracture but no difference after 7 days.

3. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1428240/full

Do NSAIDs affect bone healing rate, delay union, or cause ... The tibial shaft non-union rate is reported to be 4.6% following the same treatment, although this figure is subject to variation as some ...

4. surgicoll.scholasticahq.com surgicoll.scholasticahq.com/article/124986-the-association-of-nsaid-use-and-risk-of-adverse-fracture-healing-a-systematic-review-and-meta-analysis

The Association of NSAID Use and Risk of Adverse Fracture ... This meta-analysis indicates that the use of NSAIDs after a fracture is associated with an increased risk of ABH events, especially among fractures in adult ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8568409/

The effect of NSAIDs on postfracture bone healing: a meta- ... The risk of nonunion was higher in the patients who were given NSAIDs after the fracture with an OR of 3.47. However, once the studies were ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9945020/

Efficacy and safety of non-steroidal anti-inflammatory drugs ... The patients receiving ibuprofen had significantly less pain in the first 8 hours of treatment (2.5/10 in the first 8 hours and 1.1/10 for ...

7. link.springer.com link.springer.com/article/10.1007/s44337-024-00034-6

Comprehensive review of the impact of NSAIDs on bone ... Several studies indicate that NSAIDs have adverse effects on bone physiology, leading to delayed bone healing, impaired callus formation, and ...