Impact of NSAIDs on delayed fracture healing

INTERVENTION: BRIEF NAME: Non‐steroidal anti‐inflammatory drugs (NSAIDs) WHY: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are commonly prescribed following musculoskeletal injuries and fractures as an effective method of pain relief, and are thought to offer a safer alternative to prescription opioids which are associated with an epidemic of abuse and secondary harm. However, there is some evidence that NSAIDs may impair bone formation, and therefore impact upon fracture healing, creating delayed union or non‐union. Recent high‐quality systematic reviews on the association between NSAID use and fracture non‐union have concluded that, owing to a lack of clear evidence for impaired bone healing due to NSAID use, randomised controlled trials (RCTs) and high‐quality prospective cohort studies are still needed. Given the frequency and use of NSAIDs, it is essential that we have solid evidence to inform clinical guidelines on the use of safe and appropriate analgesia to improve patient care. In order to conduct a large multi‐site RCT to draw more definitive conclusions about the effects of NSAIDs on bone healing, it is important to firstly ascertain the safety and feasibility of conducting such a study via a pilot RCT. Therefore, the aims of this study are: 1. To determine the feasibility of using a prescribed treatment regime of NSAIDs versus a placebo in people with tibial shaft or femoral shaft limb fractures; and 2. To inform the design of a definitive multi‐site trial that aims to determine the effect of NSAIDs on rates of non‐union in people with tibial or femoral shaft limb fractures WHAT: NSAID: Parecoxib ‐ Dose: 40mg ‐ Frequency/Duration: Single dose, intra‐operative ‐ Mode: intravenous NSAID: Celecoxib ‐ Dose: 200mg ‐ Frequency/Duration: twice daily, commencing 24 hours after surgery and in the two weeks post‐surgery ‐ Mode: Oral Procedure: Participants in the intervention group will receive standard care* CONDITION: Injuries and Accidents ‐ Fractures Tibial shaft fracture;Femoral shaft fracture; ; Tibial shaft fracture ; Femoral shaft fracture PRIMARY OUTCOME: Patient Adherence will be determined via: ; ‐ Daily medication diary; ‐ Follow‐up interview where participants will be asked questions about medication adherence, any barriers to medication adherence, and satisfaction with care ; ‐ Retention rates of recruitment; [‐ Medication diary to be completed daily for two weeks post‐surgery; ‐ Follow‐up interview at two weeks post‐surgery; ] Physician Adherence will be determined via:; ‐ Drug monitoring chart (which includes name/type of drug, dosage, route of administration, date and time(s) of administration, length of exposure (in‐hospital) and details of treatment and any co‐morbidities)[First three days post‐surgery] SECONDARY OUTCOME: Adverse Events/Complications will be determined via: ; ‐ Daily diary of side‐effects ; ‐ Follow‐up interview where participants will be asked questions about adverse events/complications ; Examples of possible side‐effects of analgesic medications include: fatigue, drowsiness, inability to concentrate, nausea, dizziness, constipation, itching, difficulty urinating, retching/vomiting, skin rash, hallucinations, and gastrointestinal upset[Follow‐up interview at two weeks post‐surgery ; ] Pain Severity determined via: ; ‐ Daily pain diary (pain rated on Numeric Rating Scale)[Pain diary to be completed daily for two weeks post‐surgery] INCLUSION CRITERIA: Participants will be eligible if they meet the following INCLUSION CRITERIA: ‐ at least one tibial or femoral shaft fracture managed with either intramedullary nailing or plating ‐ an acute hospital length of stay>24 hours at The Alfred Hospital ‐ aged 18‐65 years.