Correlation Between Acute Analgesia and Long-Term Function Following Ankle Injuries
Condition: Ligament Injury
MeSH terms: Wounds and Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      In this 4-arm pragmatic randomized control trial, the investigators hope to decipher whether
      the use of non-opioid analgesics (naproxen, celecoxib, acetaminophen) in addition to
      standardized physiotherapy during the acute phase of grade I-II ankle injuries will result in
      functional differences compared to standardized physiotherapy alone
    

Detailed description: 
      Background Ankle sprains occur frequently in the Canadian Armed Forces (CAF) population and
      account for a significant proportion of lost work time. Equally significant is the use of
      analgesics (NSAID or non-NSAID) (NSAID = non steroidal anti-inflammatory drug) in the CAF
      population. Existing literature suggests that the rate and extent of soft tissue healing may
      be adversely affected by use of some analgesics, particularly non-steroidal anti-inflammatory
      agents (NSAIDs), when these are used immediately following joint injury. There have been two
      postulated mechanisms for this observation: the first being that inflammatory markers are
      required in the regeneration process; the second is that the diminished pain level as a
      result of analgesic use encourages overuse of the injured tissue. Unfortunately, the science
      is far from conclusive, since much of it is derived based on isolated exercises, conducted in
      experimental settings, in older populations, or extrapolated from biomarkers that have not
      been validated for clinical relevance. While there is no current standard of practice
      regarding the use of pain relievers following ankle injury, this practice continues to be
      widespread in the CAF.

      Goal The proposed study aims to clarify whether three commonly used non-opioid pain relievers
      provide additional benefit or delay improvement in ankle function following mild ankle
      sprains, when compared to standardized physiotherapy treatment alone. The three agents
      investigated will be 1) the non-steroid anti-inflammatory drug naproxen, 2) the selective
      anti-inflammatory celecoxib, and 3) the centrally-acting analgesic acetaminophen.

      Methods Patients presenting to the health clinic at Garrison Petawawa with acute ankle
      injuries will be screened for study eligibility. All individuals who elect to participate in
      this study will be referred for standardized physiotherapy treatment, which will be
      administered according to study protocol. Participants will also be randomized to one of four
      analgesic treatment groups (i.e., naproxen, celecoxib, acetaminophen, or non-pharmacological
      measures only), with stratification for grade of ankle injury. Physiotherapists who are
      blinded to analgesic treatment allocation will evaluate participants' ankle function at 72
      hours, 2 weeks, 3 months and 1 year post-injury, using previously validated tests.
      Pharmacists will assess response to drug therapy, side effects, and use of rescue medications
      at day 7 following enrollment. Occurrence of repeat ankle injuries and health resource
      consumption (i.e., specialist visits and diagnostic imaging) will also be assessed for the
      year following index injury.

      Risks This study is intended to be low risk to participants as it is designed to closely
      mirror existing practices for such injuries. All medications used in this study are indicated
      for soft tissue injuries and their respective dosages/frequencies/durations aligned with
      manufacturer recommendations. The physiotherapy intervention was developed by Dr. Eric
      Robitaille. It has been used in previous studies and is currently in use in the CAF. The
      investigators do not expect the risk of injury to be higher than that associated with
      existing practices for ankle injuries.

      Benefits Participants are expected to benefit from the direct application of a standardized
      physiotherapy treatment protocol for overall management of their condition as well as the
      pain relief from the analgesic options. The results of this study are expected to generate
      new information that can be readily applied to patient care, specifically in treating a
      frequently-occurring soft tissue injury in the CAF population.
    

Intervention name(s): Acetaminophen; Naproxen; Celecoxib; physiotherapy only
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): Acetaminophen 500 mg four times daily for 7 days; naproxen 500mg twice daily for 7 days; celecoxib 100mg twice daily; physiotherapy only (no drug)
Other intervention name(s): tylenol; celebrex
Intervention MeSH terms: Acetaminophen; Celecoxib; Naproxen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary purpose: Treatment