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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02667730
Recruitment Status : Recruiting
First Posted : January 29, 2016
Last Update Posted : August 9, 2018
Information provided by (Responsible Party):
Canadian Department of National Defense

Brief 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

Condition or disease Intervention/treatment Phase
Ligament Injury Drug: Acetaminophen Drug: Naproxen Drug: Celecoxib Other: physiotherapy only Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Masking Description: Patients are aware of their allocation. The treating physiotherapists will not be aware of allocation and patients are asked to not discuss their medication (allocation) with physiotherapists
Primary Purpose: Treatment
Official Title: Correlation Between Acute Analgesia and Long-Term Function Following Ankle
Study Start Date : June 2015
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Physiotherapy only
This group will receive non-pharmacological advice and physiotherapy only
Other: physiotherapy only
physiotherapy only (no drug)

Experimental: Acetaminophen + physiotherapy
This group will receive acetaminophen 500mg 4 times daily for 7 days in addition to standardized physiotherapy
Drug: Acetaminophen
Acetaminophen 500 mg four times daily for 7 days
Other Name: tylenol

Other: physiotherapy only
physiotherapy only (no drug)

Experimental: Naproxen + physiotherapy
This group will receive naproxen 500mg twice daily for 7 days in addition to standardized physiotherapy
Drug: Naproxen
naproxen 500mg twice daily for 7 days

Other: physiotherapy only
physiotherapy only (no drug)

Experimental: Celecoxib + physiotherapy
This group will receive celecoxib 100mg twice daily for 7 days in addition to standardized physiotherapy
Drug: Celecoxib
celecoxib 100mg twice daily
Other Name: celebrex

Other: physiotherapy only
physiotherapy only (no drug)

Primary Outcome Measures :
  1. Ankle Function on FAAM [ Time Frame: 3 months ]
    Foot and Ankle Abilities Measure

Secondary Outcome Measures :
  1. Pain on visual analogue scale (VAS) [ Time Frame: 3 months ]
    visual analogue scale

  2. Mobility on Wall Lunge [ Time Frame: 3 months ]
    wall lunge test for ankle mobility

  3. Laxity on anterior drawer test [ Time Frame: 3 months ]
    test for laxity

  4. Proprioception on SEBT [ Time Frame: 3 months ]
    star excursion balance test

  5. composite of health resource consumption [ Time Frame: 1 year ]
    # of orthopedic specialist consults, diagnostics, patient encounters for MSK reasons, # of days off work

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   17 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02667730

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Contact: Koren Lui, BScPHM 647 296 5121

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Canada, Ontario
2 Fd Amb medical clinic Recruiting
Petawawa, Ontario, Canada, K8H2X9
Contact: Koren Lui, BScPHM    6472965121   
Sub-Investigator: Kelly Debouter, MSc         
Sub-Investigator: Robert Reid, MD         
Sub-Investigator: Adrian Carpenter, MD         
Sub-Investigator: Eric Robitaille, PhD         
Sub-Investigator: Janice Ma, PharmD         
Sponsors and Collaborators
Canadian Department of National Defense
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Principal Investigator: Koren Lui, BScPHM Canadian Forces Health Services Group

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Responsible Party: Canadian Department of National Defense Identifier: NCT02667730     History of Changes
Other Study ID Numbers: 2013-12-126-004-0001
First Posted: January 29, 2016    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Gout Suppressants