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

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

Recruiting
18-80 years
All
Phase 3

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Overview

Two arm, pragmatic, randomized controlled multicenter Phase III noninferiority trial evaluating the efficacy of standard pain management without NSAIDs (Group 1) vs. standard pain management plus up to 6 weeks of NSAIDs (Group 2) in the treatment of tibial shaft fractures.

Description

The proposed study is a two arm, pragmatic, randomized controlled multicenter Phase III noninferiority trial. We will randomize patients with diaphyseal tibia fractures treated with intramedullary (IM) nail into two treatment arms. The control group will receive standard pain management with no NSAIDs. The treatment intervention group will receive standard pain management plus up to six weeks of NSAIDs (3 weeks of prescribed medication followed by 3 weeks of medication PRN). Our hypothesis is that pain management using up to 6 weeks of NSAIDs will result in improved pain control and lower opioid consumption but demonstrate non-inferior levels of complications compared to standard of care pain management. The aim of the study is to:

Specific Aim: Evaluate the effect of standard pain management without NSAIDs (Group 1) vs. standard pain management plus up to 6 weeks of NSAIDs (Group 2) in the treatment of tibial shaft fractures.

Primary Hypothesis: When compared to patients who received standard of care pain management, patients treated with up to 6 weeks of NSAIDs will have noninferior rates of surgery for nonunion at one year.

Secondary Hypotheses: When compared to patients who received standard of care pain management without NSAIDs, patients treated with up to 6 weeks of NSAIDs will benefit from (1) reduced opioid utilization; (2) reduced levels of persistent pain; (3) reduced pain interference; (4) improved functional outcomes; (5) noninferior rates of analgesic treatment related side effects; and (6) noninferior rates of radiographic union.

Eligibility

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.

Study details
    Tibial Fractures
    Pain

NCT07006675

Major Extremity Trauma Research Consortium

15 October 2025

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