NSAIDs plus usual pain care versus no NSAIDs after intramedullary nailing for tibia shaft fractures

Effect of NSAIDs on Union, Opioid Utilization and Pain Management for Tibia Fractures: A Pragmatic, Randomized Controlled Trial

This study will test whether adding up to six weeks of ibuprofen to usual pain care improves pain and reduces opioid use without increasing the chance of needing surgery for nonunion in adults 18–80 with a tibial shaft fracture fixed with an intramedullary nail.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1000 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Major Extremity Trauma Research Consortium (Academic / other)
• Locations: 14 sites (Indianapolis, Indiana and 13 other locations)
• Trial ID: NCT07006675 on ClinicalTrials.gov

What this trial studies

This is a pragmatic, multicenter, randomized Phase III noninferiority trial that enrolls adults with diaphyseal tibia fractures treated with intramedullary nails and randomizes them to standard pain management without NSAIDs or standard care plus up to six weeks of NSAIDs (600 mg ibuprofen). The active arm receives three weeks of prescribed medication followed by up to three weeks PRN. The primary outcome is rate of surgery for nonunion at one year, and key secondary outcomes include opioid consumption, persistent pain, pain interference, functional outcomes, and other analgesic treatments. The trial is conducted at METRC-affiliated sites with follow-up planned for 12 months.

Who should consider this trial

Good fit: Adults aged 18–80 with closed or Grade I–IIIa open diaphyseal tibia fractures treated with an intramedullary nail who can take oral NSAIDs and can be followed at a participating METRC site for 12 months.

Not a fit: Patients with contraindications to NSAIDs (recent GI bleed or perforation, prior stroke or heart attack, severe renal failure, bleeding disorders), those who require chronic NSAID/aspirin therapy, cannot take oral medications, or are current IV drug users are excluded and unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, adding short-term NSAIDs could improve pain control and lower opioid use after tibia fracture without raising rates of surgery for nonunion.

How similar studies have performed: Prior observational studies have provided mixed evidence about NSAIDs and bone healing and randomized data are limited, so this large pragmatic Phase III noninferiority trial seeks to fill an important evidence gap.

Eligibility criteria

Inclusion Criteria:

1. All patients with open (Grade I, II, of IIIa) or closed tibia fractures treated with a nail.
2. Patients 18-80 years old inclusive.
3. Patients able to be followed at a METRC facility for at least 12 months following injury

Exclusion Criteria:

1. Patient unable to provide informed consent
2. Patients who are current - intravenous drug user.
3. Patients with a history of allergy to the study drugs.
4. Patients unable to swallow oral medications or without functioning GI tract.
5. Patients with a history of gastrointestinal bleeds or gastric perforation.
6. Patients with a history of stroke or heart attack.
7. Patients requiring an aspirin or NSAID regimen except for low dose aspirin, 81mg.
8. Patients with any bleeding disorders.
9. Patients with severe renal failure \[GFR:\<30\]. Patients with moderate renal failure \[GFR: 30-59\] may participate in the study at a modified dose \[see section 8.6 for defined modified dose\].
10. Patients undergoing daily treatment with systemic glucocorticoids before surgery.
11. Patients likely to have severe problems maintaining follow-up, including patients diagnosed with a severe psychiatric conditions, patients who live too far outside the hospital's catchment area, patients who are incarcerated and patients who have unstable housing situations.
12. Patients with a GCS \<15 at discharge.
13. Patients with a closed head injury that precludes NSAIDS.
14. Patients who are pregnant or lactating at time of screening
15. Patients with a bone graft procedure planned for a future date at the time of initial definitive fixation surgery.

Where this trial is running

Indianapolis, Indiana and 13 other locations

• Eskenazi Hospital — Indianapolis, Indiana, United States (Recruiting)
• Indiana University-Methodist — Indianapolis, Indiana, United States (Recruiting)
• University of Maryland R Adams Cowley Shock Trauma Center — Baltimore, Maryland, United States (Recruiting)
• Harvard Medical Center — Cambridge, Massachusetts, United States (Recruiting)
• Hennepin Health — Minneapolis, Minnesota, United States (Recruiting)
• University of Mississippi — Jackson, Mississippi, United States (Recruiting)
• The MetroHealth System — Cleveland, Ohio, United States (Recruiting)
• Allegheny General Hospital — Pittsburgh, Pennsylvania, United States (Recruiting)
• Vanderbilt Medical Center — Nashville, Tennessee, United States (Recruiting)
• University of Texas Health Science Center - Houston — Houston, Texas, United States (Recruiting)
• University of Utah — Salt Lake City, Utah, United States (Recruiting)
• Inova Fairfax Hospital — Falls Church, Virginia, United States (Recruiting)
• University of Wisconsin — Madison, Wisconsin, United States (Recruiting)
• University of Calgary, Foothills Medical Centre — Calgary, Alberta, Canada (Recruiting)

Study contacts

• Principal investigator: Thomas Higgins, MD — University of Utah
• Study coordinator: Thomas Higgins, MD

Conditions Tibial Fractures; Pain; Ibuprofen; Pain Management; Tibia Fracture; IM Nail Fixation; NSAID