Pain, Tibial Fractures
Conditions
Keywords
Ibuprofen, Pain Management, Tibia Fracture, IM Nail Fixation, NSAID
Brief summary
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.
Detailed 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.
Interventions
DRUG600 mg Ibuprofen
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.
Sponsors
United States Department of Defense
Major Extremity Trauma Research Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Secondary surgery to promote bone union after 3 months post initial surgery | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Utilization | 1 year | 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 | 1 year | 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 | 1 year | 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 | 1 year | 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. |
| Radiographic bone union | 1 year | Radiographic union will be based on the modified RUST score44 assessed between 3 months and 12 months after definitive fixation surgery. Radiographic examinations at 3, 6 and 12 months by an adjudication committee comprised of METRC investigators will be evaluated based on AP and lateral x-rays. |
Countries
Canada, United States
Contacts
Primary ContactThomas Higgins, MD
Backup ContactKatherine Frey, PhD
Outcome results
None listed