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Correlation Between Acute Analgesia and Long-Term Function Following Ankle Injuries (CALF)

C

Canadian Department of National Defense

Status and phase

Completed
Phase 4

Conditions

Ligament Injury

Treatments

Drug: Acetaminophen
Other: physiotherapy only
Drug: Naproxen
Drug: Celecoxib

Study type

Interventional

Funder types

Other

Identifiers

NCT02667730
2013-12-126-004-0001

Details and patient eligibility

About

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

Full 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.

Enrollment

168 patients

Sex

All

Ages

17 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Acquired acute ankle injury (injured less than 48 hours ago);
  • Clinical diagnosis of a Grade I or II ankle sprain
  • Is eligible to receive comprehensive medical care from Garrison Petawawa

Exclusion criteria

  • Diagnosis of ankle fracture or ligament rupture
  • Has planned release from the Canadian Armed Forces within one year;
  • Documented restrictions on military duties
  • Has known intolerance or documented adverse reaction to acetaminophen or naproxen or celecoxib
  • Documented history of liver or kidney problems
  • pregnant or breastfeeding

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

168 participants in 4 patient groups, including a placebo group

Physiotherapy only
Placebo Comparator group
Description:
This group will receive non-pharmacological advice and physiotherapy only
Treatment:
Other: physiotherapy only
Acetaminophen + physiotherapy
Experimental group
Description:
This group will receive acetaminophen 500mg 4 times daily for 7 days in addition to standardized physiotherapy
Treatment:
Other: physiotherapy only
Drug: Acetaminophen
Naproxen + physiotherapy
Experimental group
Description:
This group will receive naproxen 500mg twice daily for 7 days in addition to standardized physiotherapy
Treatment:
Other: physiotherapy only
Drug: Naproxen
Celecoxib + physiotherapy
Experimental group
Description:
This group will receive celecoxib 100mg twice daily for 7 days in addition to standardized physiotherapy
Treatment:
Drug: Celecoxib
Other: physiotherapy only

Trial contacts and locations

1

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Central trial contact

Koren Lui, BScPHM

Data sourced from clinicaltrials.gov

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