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.
All patients with open (Grade I, II, of IIIa) or closed tibia fractures treated with a nail.
Patients 18-80 years old inclusive.
Patients able to be followed at a METRC facility for at least 12 months following injury
Patient unable to provide informed consent
Patients who are current - intravenous drug user.
Patients with a history of allergy to the study drugs.
Patients unable to swallow oral medications or without functioning GI tract.
Parallel
600 mg Ibuprofen
DrugTreatment 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.
Secondary surgery to promote bone union after 3 months post initial surgery
Bone nonunion will be assessed by the presence of a secondary surgery to promote union after 3 months and up to 12 months post definitive fixation surgery. Non-prophylactic secondary surgery to promote union will be considered evidence of nonunion. Each case will be independently reviewed by members of the METRC Central Adjudication Committee and if at least 2 members agree with the assessment of secondary surgery to promote union, no further review will be necessary. The METRC Central Adjudication Committee will convene to discuss the cases for which there is disagreement regarding non-union assessment.
Opioid Utilization
Opioid utilization will be recorded in two ways: Opiate pain medicine prescribed by the treating provider as well as self -reported opiate use by the study subjects.
Adverse Effects and Complications
Adverse effects and complications of ibuprofen include, in addition to nonunion, wound closure complications, bleeding complications, as well as pain treatment related adverse effects. Adverse effects include nausea, vomiting, dizziness, headaches, renal impairment, platelet inhibition and angioedema. In addition, on 7/9/15 the FDA released an announcement related to the risks of NSAIDS entitled, "FDA Drug Safety Communication: FDA strengthens warning that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes". 45 Consequently, consent forms for this study will include the required language and participants will be assessed for these cardiovascular outcomes.
Persistent Pain & Pain Inference
The BPI (Brief Pain Inventory) is a widely used, 15-item measure of pain intensity and interference with daily life and will be assessed at baseline, 3, 6, and 12 months post definitive fixation surgery. It has been extensively validated in both English and Spanish, and also includes questions about pain treatments and the effectiveness of these treatments.46 The BPI pain intensity domain is compatible with the IMMPACT guidelines for assessing pain in clinical trials and the FDA Guidance for Industry on the use of Patient-Reported Outcome Measures. In addition to the BPI instrument, pain inference will be collected using the Patient Report Outcomes Measurement Information System (PROMIS) as described below.
Physical and Psychosocial Function
Self -Reported Measures of Physical and Psychosocial Function will be assessed at baseline, 3, 6, and 12 months post definitive fixation surgery using the Patient Report Outcomes Measurement Information System (PROMIS) Computer Adaptive Test (CAT) item banks, a product of the NIH Roadmap for Medical Research. CATs present an advantage over traditional measures in that they target only the most relevant items to each patient and can thus be used to obtain precise measurements with 4-6 items, making assessment across multiple domains feasible. CATs can also extend the ceiling and floor of individual domains, potentially enhancing responsiveness. At any visit if a CAT cannot be administered, respondents will instead complete the appropriate short forms associated with the CAT measure.
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Major Extremity Trauma Research Consortium
Lead sponsor
United States Department of Defense
Collaborator
